Trial Outcomes & Findings for Olaparib and Onalespib in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple-Negative Breast Cancer (NCT NCT02898207)

Last Updated: 2023-04-26

Results Overview

MTD was determined by testing increasing doses of the combination of olaparib PO and onalespib IV within dose escalation cohorts consisting of 3 to 6 evaluable participants. MTD reflects the highest dose combination that did not cause a Dose-Limiting Toxicity (DLT) in \> 33% of participants. DLTs were defined based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Enrollment to this study was suspended prior to completion of the dose escalation due to discontinuation of further development of onalespib. A true single MTD therefore could not be determined. The two dose levels included in this outcome measure represent the highest well-tolerated dose combinations (Dose Level 2 \[DL2\]: Olaparib 300 mg PO BID and Onalespib 40 mg/m\^2 IV; and Dose Level 2a \[DL2a\]: Olaparib 200 mg PO BID and Onalespib 80 mg/m\^2 IV).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

28 participants

Primary outcome timeframe

Up to 35 days for each dose level cohort

Results posted on

2023-04-26

Participant Flow

Participant milestones

Participant milestones
Measure	Dose Level 0: Olaparib 200 mg and Onalespib 20 mg/m^2 Dose Level 0 (DL0): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200mg PO BID on days 1-28 and onalespib 20 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 1: Olaparib 200 mg and Onalespib 40 mg/m^2 Dose Level 1 (DL1): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200mg PO BID on days 1-28 and onalespib 40 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 2: Olaparib 300 mg and Onalespib 40 mg/m^2 Dose Level 2 (DL2): Patients received olaparib 300 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 300 mg PO BID on days 1-28 and onalespib 40 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 3: Olaparib 300 mg and Onalespib 80 mg/m^2 Dose Level 3 (DL3): Patients received olaparib 300 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 300 mg PO BID on days 1-28 and onalespib 80 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 2a: Olaparib 200 mg and Onalespib 80 mg/m^2 Dose Level 2a (DL2a): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200 mg PO BID on days 1-28 and onalespib 80 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 3a: Olaparib 200 mg and Onalespib 120 mg/m^2 Dose Level 3a (DL3a): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200 mg PO BID on days 1-28 and onalespib 120 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.
Dose Level 0 STARTED	3	0	0	0	0	0
Dose Level 0 COMPLETED	3	0	0	0	0	0
Dose Level 0 NOT COMPLETED	0	0	0	0	0	0
Dose Level 1 STARTED	0	4	0	0	0	0
Dose Level 1 COMPLETED	0	4	0	0	0	0
Dose Level 1 NOT COMPLETED	0	0	0	0	0	0
Dose Level 2 STARTED	0	0	6	0	0	0
Dose Level 2 COMPLETED	0	0	6	0	0	0
Dose Level 2 NOT COMPLETED	0	0	0	0	0	0
Dose Level 3 STARTED	0	0	0	7	0	0
Dose Level 3 COMPLETED	0	0	0	7	0	0
Dose Level 3 NOT COMPLETED	0	0	0	0	0	0
Dose Level 2a STARTED	0	0	0	0	3	0
Dose Level 2a COMPLETED	0	0	0	0	3	0
Dose Level 2a NOT COMPLETED	0	0	0	0	0	0
Dose Level 3a STARTED	0	0	0	0	0	5
Dose Level 3a COMPLETED	0	0	0	0	0	5
Dose Level 3a NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Olaparib and Onalespib in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple-Negative Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Level 0: Olaparib 200 mg and Onalespib 20 mg/m^2 n=3 Participants Dose Level 0 (DL0): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200mg PO BID on days 1-28 and onalespib 20 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 1: Olaparib 200 mg and Onalespib 40 mg/m^2 n=4 Participants Dose Level 1 (DL1): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200mg PO BID on days 1-28 and onalespib 40 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 2: Olaparib 300 mg and Onalespib 40 mg/m^2 n=6 Participants Dose Level 2 (DL2): Patients received olaparib 300 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 300 mg PO BID on days 1-28 and onalespib 40 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 3: Olaparib 300 mg and Onalespib 80 mg/m^2 n=7 Participants Dose Level 3 (DL3): Patients received olaparib 300 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 300 mg PO BID on days 1-28 and onalespib 80 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 2a: Olaparib 200 mg and Onalespib 80 mg/m^2 n=3 Participants Dose Level 2a (DL2a): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200 mg PO BID on days 1-28 and onalespib 80 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 3a: Olaparib 200 mg and Onalespib 120 mg/m^2 n=5 Participants Dose Level 3a (DL3a): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200 mg PO BID on days 1-28 and onalespib 120 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Total n=28 Participants Total of all reporting groups
Age, Continuous	59 years n=93 Participants	65 years n=4 Participants	57.5 years n=27 Participants	53 years n=483 Participants	66 years n=36 Participants	66 years n=10 Participants	65 years n=115 Participants
Sex: Female, Male Female	3 Participants n=93 Participants	4 Participants n=4 Participants	5 Participants n=27 Participants	6 Participants n=483 Participants	3 Participants n=36 Participants	5 Participants n=10 Participants	26 Participants n=115 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	2 Participants n=115 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=93 Participants	4 Participants n=4 Participants	6 Participants n=27 Participants	7 Participants n=483 Participants	3 Participants n=36 Participants	5 Participants n=10 Participants	28 Participants n=115 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) White	3 Participants n=93 Participants	2 Participants n=4 Participants	6 Participants n=27 Participants	6 Participants n=483 Participants	3 Participants n=36 Participants	5 Participants n=10 Participants	25 Participants n=115 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	2 Participants n=115 Participants
Region of Enrollment United States	3 participants n=93 Participants	4 participants n=4 Participants	6 participants n=27 Participants	7 participants n=483 Participants	3 participants n=36 Participants	5 participants n=10 Participants	28 participants n=115 Participants
ECOG Performance Status 0 = Asymptomatic and fully active	1 Participants n=93 Participants	4 Participants n=4 Participants	2 Participants n=27 Participants	4 Participants n=483 Participants	2 Participants n=36 Participants	4 Participants n=10 Participants	17 Participants n=115 Participants
ECOG Performance Status 1 = Symptomatic; fully ambulatory; restricted in physically strenuous activity	2 Participants n=93 Participants	0 Participants n=4 Participants	4 Participants n=27 Participants	3 Participants n=483 Participants	1 Participants n=36 Participants	1 Participants n=10 Participants	11 Participants n=115 Participants
Primary Site of Disease Ovary	3 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants	5 Participants n=483 Participants	3 Participants n=36 Participants	3 Participants n=10 Participants	18 Participants n=115 Participants
Primary Site of Disease Uterus	0 Participants n=93 Participants	2 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	2 Participants n=10 Participants	5 Participants n=115 Participants
Primary Site of Disease Colon	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	2 Participants n=115 Participants
Primary Site of Disease Breast	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants
Primary Site of Disease Melanoma	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants
Primary Site of Disease Malignant solitary fibrous tumor	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants
Stage at Diagnosis IC	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	1 Participants n=10 Participants	1 Participants n=115 Participants
Stage at Diagnosis IIC	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants
Stage at Diagnosis III	1 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	3 Participants n=115 Participants
Stage at Diagnosis IIIC	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	1 Participants n=10 Participants	5 Participants n=115 Participants
Stage at Diagnosis IV	2 Participants n=93 Participants	1 Participants n=4 Participants	4 Participants n=27 Participants	5 Participants n=483 Participants	2 Participants n=36 Participants	0 Participants n=10 Participants	14 Participants n=115 Participants
Stage at Diagnosis IVB	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	0 Participants n=36 Participants	3 Participants n=10 Participants	4 Participants n=115 Participants
Histology Well differentiated	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	2 Participants n=115 Participants
Histology Moderately differentiated	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	2 Participants n=115 Participants
Histology Poorly differentiated	0 Participants n=93 Participants	3 Participants n=4 Participants	2 Participants n=27 Participants	4 Participants n=483 Participants	2 Participants n=36 Participants	4 Participants n=10 Participants	15 Participants n=115 Participants
Histology Grade cannot be assessed/unknown	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants	3 Participants n=483 Participants	1 Participants n=36 Participants	1 Participants n=10 Participants	9 Participants n=115 Participants
Lines of Prior Therapy	5 Lines of prior therapy n=93 Participants	3 Lines of prior therapy n=4 Participants	5.5 Lines of prior therapy n=27 Participants	6 Lines of prior therapy n=483 Participants	7 Lines of prior therapy n=36 Participants	3 Lines of prior therapy n=10 Participants	5.5 Lines of prior therapy n=115 Participants

PRIMARY outcome

Timeframe: Up to 35 days for each dose level cohort

Population: Seven of the 28 patients were not evaluable for DLT assessment and were replaced.

Outcome measures

Outcome measures
Measure	All Evaluable Participants n=21 Participants All participants who received at least 75% of planned olaparib and at least 4 doses of onalespib within the DLT period.	Dose Level 1: Olaparib 200 mg and Onalespib 40 mg/m^2 Dose Level 1 (DL1): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200mg PO BID on days 1-28 and onalespib 40 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 2: Olaparib 300 mg and Onalespib 40 mg/m^2 Dose Level 2 (DL2): Patients received olaparib 300 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 300 mg PO BID on days 1-28 and onalespib 40 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 3: Olaparib 300 mg and Onalespib 80 mg/m^ Dose Level 3 (DL3): Patients received olaparib 300 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 300 mg PO BID on days 1-28 and onalespib 80 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 2a: Olaparib 200 mg and Onalespib 80 mg/m^2 Dose Level 2a (DL2a): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200 mg PO BID on days 1-28 and onalespib 80 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 3a: Olaparib 200 mg and Onalespib 120 mg/m^2 Dose Level 3a (DL3a): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200 mg PO BID on days 1-28 and onalespib 120 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.
Maximum Tolerated Dose (MTD) of Olaparib Administered in Combination With Onalespib Dose Level 2 Olaparib PO BID	300 mg	—	—	—	—	—
Maximum Tolerated Dose (MTD) of Olaparib Administered in Combination With Onalespib Dose Level 2a Olaparib PO BID	200 mg	—	—	—	—	—

PRIMARY outcome

Timeframe: Up to 35 days for each dose level cohort

Population: Seven of the 28 patients were not evaluable for DLT assessment and were replaced.

Outcome measures

Outcome measures
Measure	All Evaluable Participants n=21 Participants All participants who received at least 75% of planned olaparib and at least 4 doses of onalespib within the DLT period.	Dose Level 1: Olaparib 200 mg and Onalespib 40 mg/m^2 Dose Level 1 (DL1): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200mg PO BID on days 1-28 and onalespib 40 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 2: Olaparib 300 mg and Onalespib 40 mg/m^2 Dose Level 2 (DL2): Patients received olaparib 300 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 300 mg PO BID on days 1-28 and onalespib 40 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 3: Olaparib 300 mg and Onalespib 80 mg/m^ Dose Level 3 (DL3): Patients received olaparib 300 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 300 mg PO BID on days 1-28 and onalespib 80 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 2a: Olaparib 200 mg and Onalespib 80 mg/m^2 Dose Level 2a (DL2a): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200 mg PO BID on days 1-28 and onalespib 80 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 3a: Olaparib 200 mg and Onalespib 120 mg/m^2 Dose Level 3a (DL3a): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200 mg PO BID on days 1-28 and onalespib 120 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.
Maximum Tolerated Dose (MTD) of Onalespib Administered in Combination With Olaparib Dose Level 2 Onalespib IV on Days 1, 2, 8, 9, 15, and 16	40 mg/m2	—	—	—	—	—
Maximum Tolerated Dose (MTD) of Onalespib Administered in Combination With Olaparib Dose Level 2a Onalespib IV on Days 1, 2, 8, 9, 15, and 16	80 mg/m2	—	—	—	—	—

SECONDARY outcome

Timeframe: Within Cycles 0 and 1 (up to 35 days).

Population: Patients were considered not evaluable for the DLT outcome if they did not receive at least 75% of the planned olaparib doses or at least 4 doses of onalespib for reasons other than toxicity or DLT. Dose Level 3a did not complete evaluation as enrollment was suspended due to discontinuation of further development of onalespib.

DLTs were based on the NCI Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 and were defined as any grade 3 or 4 non-hematologic toxicity (excluding grade 3: fatigue; diarrhea, constipation, and nausea and/or vomiting controlled with supportive measured within 24 hours; hypophosphatemia; hyponatremia; hypomagnesemia; and rash that resolves to \< grade 3 within \< 5 days), grade 4 neutropenia of \> 7 day duration, febrile neutropenia, grade 4 thrombocytopenia or bleeding associated with grade 3 thrombocytopenia, requirement for repeated blood transfusion within 4-6 weeks, any other grade 4 hematologic toxicity, any study treatment-related death, any grade 3 or 4 event considered to be dose-limiting in the opinion of the investigator, and the inability to take 75% or more of the planned dose for olaparib and 4 out of 6 doses for onalespib within the DLT period due to treatment-related adverse events.

Outcome measures

Outcome measures
Measure	All Evaluable Participants n=3 Participants All participants who received at least 75% of planned olaparib and at least 4 doses of onalespib within the DLT period.	Dose Level 1: Olaparib 200 mg and Onalespib 40 mg/m^2 n=3 Participants Dose Level 1 (DL1): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200mg PO BID on days 1-28 and onalespib 40 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 2: Olaparib 300 mg and Onalespib 40 mg/m^2 n=3 Participants Dose Level 2 (DL2): Patients received olaparib 300 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 300 mg PO BID on days 1-28 and onalespib 40 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 3: Olaparib 300 mg and Onalespib 80 mg/m^ n=5 Participants Dose Level 3 (DL3): Patients received olaparib 300 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 300 mg PO BID on days 1-28 and onalespib 80 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 2a: Olaparib 200 mg and Onalespib 80 mg/m^2 n=3 Participants Dose Level 2a (DL2a): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200 mg PO BID on days 1-28 and onalespib 80 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 3a: Olaparib 200 mg and Onalespib 120 mg/m^2 n=4 Participants Dose Level 3a (DL3a): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200 mg PO BID on days 1-28 and onalespib 120 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 67 weeks

Population: One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.

Treatment-related toxicities in this outcome include non-hematologic and hematologic adverse events that were either Grade 3+ or occurred in at least 10% of all treated participants, and were considered at least possibly related to olaparib and/or onalespib. Adverse events were graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v.5.0.

Outcome measures

Outcome measures
Measure	All Evaluable Participants n=3 Participants All participants who received at least 75% of planned olaparib and at least 4 doses of onalespib within the DLT period.	Dose Level 1: Olaparib 200 mg and Onalespib 40 mg/m^2 n=4 Participants Dose Level 1 (DL1): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200mg PO BID on days 1-28 and onalespib 40 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 2: Olaparib 300 mg and Onalespib 40 mg/m^2 n=7 Participants Dose Level 2 (DL2): Patients received olaparib 300 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 300 mg PO BID on days 1-28 and onalespib 40 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 3: Olaparib 300 mg and Onalespib 80 mg/m^ n=6 Participants Dose Level 3 (DL3): Patients received olaparib 300 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 300 mg PO BID on days 1-28 and onalespib 80 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 2a: Olaparib 200 mg and Onalespib 80 mg/m^2 n=3 Participants Dose Level 2a (DL2a): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200 mg PO BID on days 1-28 and onalespib 80 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 3a: Olaparib 200 mg and Onalespib 120 mg/m^2 n=5 Participants Dose Level 3a (DL3a): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200 mg PO BID on days 1-28 and onalespib 120 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.
Number of Participants Who Experienced Treatment-Related Toxicities Anorexia : Maximum Grade 1-2	1 Participants	1 Participants	1 Participants	0 Participants	1 Participants	1 Participants
Number of Participants Who Experienced Treatment-Related Toxicities Diarrhea : Maximum Grade 1-2	3 Participants	3 Participants	3 Participants	5 Participants	3 Participants	4 Participants
Number of Participants Who Experienced Treatment-Related Toxicities Diarrhea : Maximum Grade 3	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants Who Experienced Treatment-Related Toxicities Nausea : Maximum Grade 1-2	1 Participants	2 Participants	4 Participants	6 Participants	3 Participants	2 Participants
Number of Participants Who Experienced Treatment-Related Toxicities Nausea : Maximum Grade 3	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Who Experienced Treatment-Related Toxicities Anemia : Maximum Grade 1-2	2 Participants	3 Participants	2 Participants	4 Participants	1 Participants	1 Participants
Number of Participants Who Experienced Treatment-Related Toxicities Anemia : Maximum Grade 3	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	3 Participants
Number of Participants Who Experienced Treatment-Related Toxicities Thrombocytopenia/platelet count decrease : Maximum Grade 1-2	0 Participants	3 Participants	1 Participants	3 Participants	0 Participants	3 Participants
Number of Participants Who Experienced Treatment-Related Toxicities Thrombocytopenia/platelet count decrease : Maximum Grade 3	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants Who Experienced Treatment-Related Toxicities Fatigue : Maximum Grade 1-2	1 Participants	3 Participants	3 Participants	2 Participants	1 Participants	2 Participants
Number of Participants Who Experienced Treatment-Related Toxicities Vomiting : Maximum Grade 1-2	1 Participants	1 Participants	3 Participants	2 Participants	1 Participants	0 Participants
Number of Participants Who Experienced Treatment-Related Toxicities Vomiting : Maximum Grade 3	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Who Experienced Treatment-Related Toxicities Abdominal pain : Maximum Grade 1-2	1 Participants	1 Participants	0 Participants	0 Participants	2 Participants	0 Participants
Number of Participants Who Experienced Treatment-Related Toxicities Abdominal pain : Maximum Grade 3	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Who Experienced Treatment-Related Toxicities Neutrophil count decreased : Maximum Grade 1-2	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants
Number of Participants Who Experienced Treatment-Related Toxicities Neutrophil count decreased : Maximum Grade 4	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants Who Experienced Treatment-Related Toxicities Lymphocyte count decreased : Maximum Grade 1-2	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants
Number of Participants Who Experienced Treatment-Related Toxicities Lymphocyte count decreased : Maximum Grade 3	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants Who Experienced Treatment-Related Toxicities Floaters : Maximum Grade 1-2	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	2 Participants
Number of Participants Who Experienced Treatment-Related Toxicities Dysgeusia : Maximum Grade 1-2	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 63 weeks

Population: Only participants who had their disease re-evaluated via CT or MRI were considered evaluable for response. Six of the 28 participants were taken off study therapy prior to their first on-study disease evaluation.

Responses determined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI, where Objective Response (OR) represents either a Complete Response (CR; disappearance of all target lesions) or a Partial Response (PR; at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum diameters).

Outcome measures

Outcome measures
Measure	All Evaluable Participants n=3 Participants All participants who received at least 75% of planned olaparib and at least 4 doses of onalespib within the DLT period.	Dose Level 1: Olaparib 200 mg and Onalespib 40 mg/m^2 n=3 Participants Dose Level 1 (DL1): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200mg PO BID on days 1-28 and onalespib 40 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 2: Olaparib 300 mg and Onalespib 40 mg/m^2 n=3 Participants Dose Level 2 (DL2): Patients received olaparib 300 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 300 mg PO BID on days 1-28 and onalespib 40 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 3: Olaparib 300 mg and Onalespib 80 mg/m^ n=6 Participants Dose Level 3 (DL3): Patients received olaparib 300 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 300 mg PO BID on days 1-28 and onalespib 80 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 2a: Olaparib 200 mg and Onalespib 80 mg/m^2 n=3 Participants Dose Level 2a (DL2a): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200 mg PO BID on days 1-28 and onalespib 80 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 3a: Olaparib 200 mg and Onalespib 120 mg/m^2 n=4 Participants Dose Level 3a (DL3a): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200 mg PO BID on days 1-28 and onalespib 120 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.
Number of Participants With Objective Responses by RECIST 1.1	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 24 weeks

Responses determined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI, where Progressive Disease (PD) represents (relative to baseline) at least a 20% increase in the sum of diameters of target lesions, appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. The duration of progression-free status was defined as the interval from the date of enrollment to date of either PD or date of last disease assessment.

Outcome measures

Outcome measures
Measure	All Evaluable Participants n=3 Participants All participants who received at least 75% of planned olaparib and at least 4 doses of onalespib within the DLT period.	Dose Level 1: Olaparib 200 mg and Onalespib 40 mg/m^2 n=3 Participants Dose Level 1 (DL1): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200mg PO BID on days 1-28 and onalespib 40 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 2: Olaparib 300 mg and Onalespib 40 mg/m^2 n=3 Participants Dose Level 2 (DL2): Patients received olaparib 300 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 300 mg PO BID on days 1-28 and onalespib 40 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 3: Olaparib 300 mg and Onalespib 80 mg/m^ n=6 Participants Dose Level 3 (DL3): Patients received olaparib 300 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 300 mg PO BID on days 1-28 and onalespib 80 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 2a: Olaparib 200 mg and Onalespib 80 mg/m^2 n=3 Participants Dose Level 2a (DL2a): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200 mg PO BID on days 1-28 and onalespib 80 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.	Dose Level 3a: Olaparib 200 mg and Onalespib 120 mg/m^2 n=4 Participants Dose Level 3a (DL3a): Patients received olaparib 200 mg PO BID on days 1-7 (cycle 0). Beginning in cycle 1, patients received olaparib 200 mg PO BID on days 1-28 and onalespib 120 mg/m\^2 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity.
Number of Participants Progression-Free for At Least 24 Weeks by RECIST 1.1	1 Participants	2 Participants	1 Participants	1 Participants	1 Participants	1 Participants

Adverse Events

Dose Level 0

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Dose Level 1

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Dose Level 2

Serious events: 4 serious events

Other events: 7 other events

Deaths: 0 deaths

Dose Level 3

Serious events: 2 serious events

Other events: 6 other events

Deaths: 1 deaths

Dose Level 2a

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Dose Level 3a

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dose Level 0 n=3 participants at risk Cycle 0 Dose: Olaparib 200 mg PO BID; Cycle 1+ Dose: Olaparib 200 mg PO BID, Onalespib 20 mg/m2 IV on days 1, 2, 8, 9, 15, and 16	Dose Level 1 n=4 participants at risk Cycle 0 Dose: Olaparib 200 mg PO BID; Cycle 1+ Dose: Olaparib 200 mg PO BID, Onalespib 40 mg/m2 IV on days 1, 2, 8, 9, 15, and 16	Dose Level 2 n=7 participants at risk Cycle 0 Dose: Olaparib 300 mg PO BID; Cycle 1+ Dose: Olaparib 300 mg PO BID, Onalespib 40 mg/m2 IV on days 1, 2, 8, 9, 15, and 16	Dose Level 3 n=6 participants at risk Cycle 0 Dose: Olaparib 300 mg PO BID; Cycle 1+ Dose: Olaparib 300 mg PO BID, Onalespib 80 mg/m2 IV on days 1, 2, 8, 9, 15, and 16	Dose Level 2a n=3 participants at risk Cycle 0 Dose: Olaparib 200 mg PO BID; Cycle 1+ Dose: Olaparib 200 mg PO BID, Onalespib 80 mg/m2 IV on days 1, 2, 8, 9, 15, and 16	Dose Level 3a n=5 participants at risk Cycle 0 Dose: Olaparib 200 mg PO BID; Cycle 1+ Dose: Olaparib 200 mg PO BID, Onalespib 120 mg/m2 IV on days 1, 2, 8, 9, 15, and 16
Blood and lymphatic system disorders Anemia	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 2/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Cardiac disorders Pericardial effusion	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Cardiac disorders Pericardial tamponade	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Cardiac disorders Sinus tachycardia	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
General disorders General and admin site - Other - Disease Progression	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Abdominal pain	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	28.6% 2/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Ascites	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Colonic obstruction	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Constipation	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Diarrhea	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Nausea	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Rectal pain	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	28.6% 2/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Small intestinal perforation	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Vomiting	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Investigations Neutrophil count decreased	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Musculoskeletal and connective tissue disorders Flank pain	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Nervous system disorders Nervous system - Other - Brain Mets	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Renal and urinary disorders Urinary tract obstruction	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Respiratory, thoracic and mediastinal disorders Dyspnea	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Respiratory, thoracic and mediastinal disorders Pleural effusion	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Respiratory, thoracic and mediastinal disorders Resp, thoracic & mediast - Other - Pulmonary Embous	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Vascular disorders Hypotension	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.

Other adverse events

Other adverse events
Measure	Dose Level 0 n=3 participants at risk Cycle 0 Dose: Olaparib 200 mg PO BID; Cycle 1+ Dose: Olaparib 200 mg PO BID, Onalespib 20 mg/m2 IV on days 1, 2, 8, 9, 15, and 16	Dose Level 1 n=4 participants at risk Cycle 0 Dose: Olaparib 200 mg PO BID; Cycle 1+ Dose: Olaparib 200 mg PO BID, Onalespib 40 mg/m2 IV on days 1, 2, 8, 9, 15, and 16	Dose Level 2 n=7 participants at risk Cycle 0 Dose: Olaparib 300 mg PO BID; Cycle 1+ Dose: Olaparib 300 mg PO BID, Onalespib 40 mg/m2 IV on days 1, 2, 8, 9, 15, and 16	Dose Level 3 n=6 participants at risk Cycle 0 Dose: Olaparib 300 mg PO BID; Cycle 1+ Dose: Olaparib 300 mg PO BID, Onalespib 80 mg/m2 IV on days 1, 2, 8, 9, 15, and 16	Dose Level 2a n=3 participants at risk Cycle 0 Dose: Olaparib 200 mg PO BID; Cycle 1+ Dose: Olaparib 200 mg PO BID, Onalespib 80 mg/m2 IV on days 1, 2, 8, 9, 15, and 16	Dose Level 3a n=5 participants at risk Cycle 0 Dose: Olaparib 200 mg PO BID; Cycle 1+ Dose: Olaparib 200 mg PO BID, Onalespib 120 mg/m2 IV on days 1, 2, 8, 9, 15, and 16
Gastrointestinal disorders Diarrhea	100.0% 3/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	75.0% 3/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	57.1% 4/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	66.7% 4/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	100.0% 3/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	100.0% 5/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Nausea	66.7% 2/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	75.0% 3/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	85.7% 6/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	100.0% 6/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	100.0% 3/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	40.0% 2/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Blood and lymphatic system disorders Anemia	66.7% 2/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	75.0% 3/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	71.4% 5/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	83.3% 5/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	66.7% 2/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	80.0% 4/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
General disorders Fatigue	66.7% 2/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	75.0% 3/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	57.1% 4/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	50.0% 3/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	40.0% 2/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Vomiting	66.7% 2/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	50.0% 2/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	71.4% 5/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 2/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Investigations Platelet count decreased	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	75.0% 3/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	66.7% 4/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	80.0% 4/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Abdominal pain	66.7% 2/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	75.0% 3/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	42.9% 3/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	66.7% 2/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Metabolism and nutrition disorders Anorexia	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	42.9% 3/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	66.7% 2/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	40.0% 2/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Metabolism and nutrition disorders Hypomagnesemia	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	50.0% 2/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	28.6% 2/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	50.0% 3/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Investigations Creatinine increased	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	28.6% 2/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	50.0% 2/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 2/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Constipation	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	28.6% 2/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 2/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Investigations Lymphocyte count decreased	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 2/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	40.0% 2/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Respiratory, thoracic and mediastinal disorders Dyspnea	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 2/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Eye disorders Floaters	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	40.0% 2/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Bloating	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Nervous system disorders Dysgeusia	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	40.0% 2/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Nervous system disorders Headache	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Metabolism and nutrition disorders Hypoalbuminemia	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Investigations Neutrophil count decreased	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	40.0% 2/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
General disorders Pain	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Investigations AST increased	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Investigations Alkaline phosphatase increased	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Ascites	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Nervous system disorders Dizziness	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	50.0% 2/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Dyspepsia	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
General disorders Edema limbs	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	28.6% 2/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Psychiatric disorders Insomnia	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 2/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Respiratory, thoracic and mediastinal disorders Nasal congestion	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 2/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Musculoskeletal and connective tissue disorders Pain in extremity	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	28.6% 2/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Investigations Weight loss	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Investigations ALT increased	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Investigations Blood bilirubin increased	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Colonic obstruction	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Dry mouth	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Musculoskeletal and connective tissue disorders Flank pain	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Respiratory, thoracic and mediastinal disorders Hiccups	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Vascular disorders Hot flashes	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Toothache	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Renal and urinary disorders Urinary tract obstruction	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Immune system disorders Allergic reaction	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Psychiatric disorders Anxiety	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Blood and lymphatic system disorders Blood/Lymph - Other - Low Iron	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Musculoskeletal and connective tissue disorders Chest wall pain	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Cardiac disorders Pericardial effusion	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Dental caries	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Eye disorders Flashing lights	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify - Belching	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify - Burping/Belching	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
General disorders General and admin site - Other - Disease Progression	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
General disorders General and admin site - Other - Increased Phelgm	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
General disorders General and admin site - Other - Lightheaded	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Renal and urinary disorders Hematuria	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Respiratory, thoracic and mediastinal disorders Hoarseness	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Vascular disorders Hypotension	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Infections and infestations Infections and infestations - Other - Fungal	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Infections and infestations Infections and infestations - Other - Pneumonia	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Infections and infestations Infections and infestations - Other - Sinus Infection	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Investigations Investigations - Other, specify - Taste Changes	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Infections and infestations Lip infection	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Metabolism and nutrition disorders Metabolism and nutrition - Other - Altered Taste	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Mucositis oral	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Musculoskeletal and connective tissue disorders Musculoskel/connect tissue -Other - Intermittent Muscle Cramps	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Musculoskeletal and connective tissue disorders Musculoskel/connect tissue -Other - Muscle Cramps	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Nervous system disorders Nervous system disorders - Other - Brain Mets	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Nervous system disorders Nervous system disorders - Other - Night Sweats	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Nervous system disorders Nervous system disorders - Other - Nightmares	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Nervous system disorders Nervous system disorders - Other - Shakiness	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Nervous system disorders Paresthesia	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Cardiac disorders Pericardial tamponade	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Skin and subcutaneous tissue disorders Photosensitivity	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Respiratory, thoracic and mediastinal disorders Pleural effusion	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Nervous system disorders Presyncope	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Rectal hemorrhage	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Rectal pain	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Renal and urinary disorders Renal and urinary disorders - Other - Bladder Pressure	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Respiratory, thoracic and mediastinal disorders Resp, thoracic & mediast - Other - Cold Symptoms	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Respiratory, thoracic and mediastinal disorders Resp, thoracic & mediast - Other - Increased Phlegm	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Respiratory, thoracic and mediastinal disorders Resp, thoracic & mediast - Other - Pneumonia	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Respiratory, thoracic and mediastinal disorders Resp, thoracic & mediast - Other - Pulmonary Embous	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Cardiac disorders Sinus tachycardia	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Skin and subcutaneous tissue disorders Skin & subcutaneous tissue -Other - Night Sweats	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	16.7% 1/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Small intestinal perforation	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Nervous system disorders Spasticity	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Surgical and medical procedures Surgical and medical - Other - Colectomy	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	25.0% 1/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Infections and infestations Upper respiratory infection	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	14.3% 1/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Renal and urinary disorders Urinary frequency	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Renal and urinary disorders Urinary urgency	33.3% 1/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.
Investigations White blood cell decreased	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/4 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/7 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/6 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	0.00% 0/3 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.	20.0% 1/5 • Adverse events data was collected throughout study participation for all patients from first administration through 30 days of the last administration of the investigational agent(s), up to 67 weeks. One patient was enrolled under Dose Level 3, but was erroneously treated at Dose Level 2. This patient was replaced within the dose escalation, but remained on treatment on Dose Level 2 throughout the remainder of trial participation. For the purposes of adverse event reporting, this patient has been included in Dose Level 2.

Additional Information

Dr. Panagiotis Konstantinopoulos

Dana-Farber Cancer Institute

Phone: 617-632-5269

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60