Trial Outcomes & Findings for Nivolumab and Ipilimumab in Treating Patients With Metastatic/Recurrent ACC of All Sites and Non-ACC Salivary Gland Cancer (NCT NCT03146650)

NCT ID: NCT03146650

Last Updated: 2024-01-18

Results Overview

Progression-Free Survival assessed per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria at time of first study treatment. PFS defined as absence of death and of progressive disease. Progressive disease per RECIST v. 1.1 defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (0.5 cm). The appearance of one or more new lesions is also considered progression. Response rates and 95% confidence intervals will be calculated using exact binomial probability distributions for discrete outcomes. Efficacy will be evaluated in all patients who receive at least one dose of study treatment and have had their disease re-evaluated.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE2
• Target enrollment: 25 participants
• Primary outcome timeframe: From the start of treatment and every 12 weeks during treatment, for up to two years, where 1 cycle =12 weeks/84 days, and range of cycles attempted was 1-11.
• Results posted on: 2024-01-18

Participant Flow

Opened for accrual on May 19, 2017 with goal of 63 patients. The first patient started treatment June 12, 2017. The study closed Aug. 9, 2019 without meeting the total accrual goal due to the pharma company deciding to close the study.

Participant milestones

Measure	Nivolumab + Ipilimumab Nivolumab and ipilimumab combination will be administered intravenously until disease progression or intolerable toxicity. Nivolumab: Given at 240mg over 30 minutes (-5 / +15 minutes) every 2 weeks starting with Cycle 1 Day 1 for the first 16 weeks (1 cycle = 12 weeks). Starting with Cycle 2 Day 29, nivolumab will be given at 480mg IV over 60 minutes (-10 / +15 minutes) every 4 weeks. Ipilimumab: Given at 1mg/Kg every 6 weeks starting with Cycle 1 Day 1 over approximately 90 minutes (-5 / +15 minutes). On days when both nivolumab and ipilimumab are administered, nivolumab should be given first, followed by ipilimumab about 30 minutes after completion of nivolumab. Patients will be assessed for response every 12 weeks (±7 days).
Registered for Study STARTED	25
Registered for Study Received First Dose of Study Drug	24
Registered for Study COMPLETED	24
Registered for Study NOT COMPLETED	1
Completed Cycle 1 of Treatment(Nivo+Ipi) STARTED	24
Completed Cycle 1 of Treatment(Nivo+Ipi) COMPLETED	23
Completed Cycle 1 of Treatment(Nivo+Ipi) NOT COMPLETED	1
Continued to Cycle 2 and Beyond STARTED	23
Continued to Cycle 2 and Beyond Reached First Response Assessment	23
Continued to Cycle 2 and Beyond Received Cycle 2 Dose of Study Drugs	21
Continued to Cycle 2 and Beyond COMPLETED	19
Continued to Cycle 2 and Beyond NOT COMPLETED	4
2 Year Follow-up STARTED	22
2 Year Follow-up COMPLETED	3
2 Year Follow-up NOT COMPLETED	19

Reasons for withdrawal

Measure	Nivolumab + Ipilimumab Nivolumab and ipilimumab combination will be administered intravenously until disease progression or intolerable toxicity. Nivolumab: Given at 240mg over 30 minutes (-5 / +15 minutes) every 2 weeks starting with Cycle 1 Day 1 for the first 16 weeks (1 cycle = 12 weeks). Starting with Cycle 2 Day 29, nivolumab will be given at 480mg IV over 60 minutes (-10 / +15 minutes) every 4 weeks. Ipilimumab: Given at 1mg/Kg every 6 weeks starting with Cycle 1 Day 1 over approximately 90 minutes (-5 / +15 minutes). On days when both nivolumab and ipilimumab are administered, nivolumab should be given first, followed by ipilimumab about 30 minutes after completion of nivolumab. Patients will be assessed for response every 12 weeks (±7 days).
Registered for Study Did not continue to meet protocol eligibility criteria after registration.	1
Completed Cycle 1 of Treatment(Nivo+Ipi) Adverse Event	1
Continued to Cycle 2 and Beyond Still on treatment	2
Continued to Cycle 2 and Beyond Progressive Disease	2
2 Year Follow-up Death	11
2 Year Follow-up Still in follow-up	7
2 Year Follow-up Lost to Follow-up	1

Baseline Characteristics

Nivolumab and Ipilimumab in Treating Patients With Metastatic/Recurrent ACC of All Sites and Non-ACC Salivary Gland Cancer

Baseline characteristics by cohort

Measure	Nivolumab + Ipilimumab n=24 Participants Nivolumab and ipilimumab combination will be administered intravenously until disease progression or intolerable toxicity. Nivolumab: Given at 240mg over 30 minutes (-5 / +15 minutes) every 2 weeks starting with Cycle 1 Day 1 for the first 16 weeks (1 cycle = 12 weeks). Starting with Cycle 2 Day 29, nivolumab will be given at 480mg IV over 60 minutes (-10 / +15 minutes) every 4 weeks. Ipilimumab: Given at 1mg/Kg every 6 weeks starting with Cycle 1 Day 1 over approximately 90 minutes (-5 / +15 minutes). On days when both nivolumab and ipilimumab are administered, nivolumab should be given first, followed by ipilimumab about 30 minutes after completion of nivolumab. Patients will be assessed for response every 12 weeks (±7 days).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	18 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	22 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	24 participants n=5 Participants
adenoid cystic carcinoma vs non-adenoid cystic carcinoma Adenoid Cystic Carcinoma	19 Participants n=5 Participants
adenoid cystic carcinoma vs non-adenoid cystic carcinoma Non-Adenoid Cystic Carcinoma	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the start of treatment and every 12 weeks during treatment, for up to two years, where 1 cycle =12 weeks/84 days, and range of cycles attempted was 1-11.

Population: Patients with recurrent or metastatic Adenoid cystic carcinoma (ACC).

Progression-Free Survival assessed per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria at time of first study treatment. PFS defined as absence of death and of progressive disease. Progressive disease per RECIST v. 1.1 defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (0.5 cm). The appearance of one or more new lesions is also considered progression. Response rates and 95% confidence intervals will be calculated using exact binomial probability distributions for discrete outcomes. Efficacy will be evaluated in all patients who receive at least one dose of study treatment and have had their disease re-evaluated.

Outcome measures

Measure	Nivolumab + Ipilimumab n=19 Participants Nivolumab and ipilimumab combination will be administered intravenously until disease progression or intolerable toxicity. Nivolumab: Given at 240mg over 30 minutes (-5 / +15 minutes) every 2 weeks starting with Cycle 1 Day 1 for the first 16 weeks (1 cycle = 12 weeks). Starting with Cycle 2 Day 29, nivolumab will be given at 480mg IV over 60 minutes (-10 / +15 minutes) every 4 weeks. Ipilimumab: Given at 1mg/Kg every 6 weeks starting with Cycle 1 Day 1 over approximately 90 minutes (-5 / +15 minutes). On days when both nivolumab and ipilimumab are administered, nivolumab should be given first, followed by ipilimumab about 30 minutes after completion of nivolumab. Patients will be assessed for response every 12 weeks (±7 days).
Progression-Free Survival progression free survival (12 months)	47.37 percentage of participants Interval 29.49 to 76.09
Progression-Free Survival progression free survival (6 months)	63.16 percentage of participants Interval 44.8 to 89.04

PRIMARY outcome

Timeframe: From the start of treatment and every 12 weeks during treatment, for up to two years, where 1 cycle =12 weeks/84 days, and range of cycles attempted was 1-11.

Population: Patients with adenoid cystic carcinoma only.

Progression-Free Survival assessed per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria at time of first study treatment. PFS defined as absence of death and of progressive disease. Progressive disease per RECIST v. 1.1 defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (0.5 cm). The appearance of one or more new lesions is also considered progression. Response rates and 95% confidence intervals will be calculated using exact binomial probability distributions for discrete outcomes. Efficacy will be evaluated in all patients who receive at least one dose of study treatment and have had their disease re-evaluated.

Outcome measures

Measure

Nivolumab + Ipilimumab n=19 Participants Nivolumab and ipilimumab combination will be administered intravenously until disease progression or intolerable toxicity. Nivolumab: Given at 240mg over 30 minutes (-5 / +15 minutes) every 2 weeks starting with Cycle 1 Day 1 for the first 16 weeks (1 cycle = 12 weeks). Starting with Cycle 2 Day 29, nivolumab will be given at 480mg IV over 60 minutes (-10 / +15 minutes) every 4 weeks. Ipilimumab: Given at 1mg/Kg every 6 weeks starting with Cycle 1 Day 1 over approximately 90 minutes (-5 / +15 minutes). On days when both nivolumab and ipilimumab are administered, nivolumab should be given first, followed by ipilimumab about 30 minutes after completion of nivolumab. Patients will be assessed for response every 12 weeks (±7 days).

Median Progression-free Survival

8.28 months Interval 5.49 to 27.99

SECONDARY outcome

Timeframe: On Cycle 2 Day 1, and every cycle thereafter (1 cycle = 12 weeks), about 27 months

Population: Adenoid Cystic Carcinoma (ACC) patient only.

Response rate (RR) is percentage of patients whose cancer shrinks or disappears after treatment. Patients with adenoid cystic carcinoma who have a complete response (CR) or partial response (PR) per RECIST criteria v. 1.1 will be included in the results. Per RECIST v. 1.1, CR is defined as "disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm." A PR is defined as "At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters."

Outcome measures

Measure

Nivolumab + Ipilimumab n=18 Participants Nivolumab and ipilimumab combination will be administered intravenously until disease progression or intolerable toxicity. Nivolumab: Given at 240mg over 30 minutes (-5 / +15 minutes) every 2 weeks starting with Cycle 1 Day 1 for the first 16 weeks (1 cycle = 12 weeks). Starting with Cycle 2 Day 29, nivolumab will be given at 480mg IV over 60 minutes (-10 / +15 minutes) every 4 weeks. Ipilimumab: Given at 1mg/Kg every 6 weeks starting with Cycle 1 Day 1 over approximately 90 minutes (-5 / +15 minutes). On days when both nivolumab and ipilimumab are administered, nivolumab should be given first, followed by ipilimumab about 30 minutes after completion of nivolumab. Patients will be assessed for response every 12 weeks (±7 days).

Response Rate (RR)

.06 percent of participants Interval 0.01 to 0.26

SECONDARY outcome

Timeframe: On Cycle 2 Day 1, and every cycle thereafter (1 cycle = 12 weeks), about 27 months

Population: Patients with Adenoid cystic carcinoma only.

Clinical Benefit Rate (CBR) is defined as the percentage of patients with Complete Response (CR), Partial Response (PR), and Stable Disease (SD) and will be assessed by RECIST 1.1 in patients with adenoid cystic carcinoma (ACC). Per RECIST v. 1.1, CR is defined as, "Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm." PR is defined as, "At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters." SD is defined as, "Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study."

Outcome measures

Measure

Nivolumab + Ipilimumab n=18 Participants Nivolumab and ipilimumab combination will be administered intravenously until disease progression or intolerable toxicity. Nivolumab: Given at 240mg over 30 minutes (-5 / +15 minutes) every 2 weeks starting with Cycle 1 Day 1 for the first 16 weeks (1 cycle = 12 weeks). Starting with Cycle 2 Day 29, nivolumab will be given at 480mg IV over 60 minutes (-10 / +15 minutes) every 4 weeks. Ipilimumab: Given at 1mg/Kg every 6 weeks starting with Cycle 1 Day 1 over approximately 90 minutes (-5 / +15 minutes). On days when both nivolumab and ipilimumab are administered, nivolumab should be given first, followed by ipilimumab about 30 minutes after completion of nivolumab. Patients will be assessed for response every 12 weeks (±7 days).

Clinical Benefit Rate (CBR)

0.71 percent of participants Interval 0.47 to 0.87

SECONDARY outcome

Timeframe: Up to 2 years from start of treatment

Population: Patients with Adenoid Cystic Carcinoma only.

Overall survival (OS) is defined as time in months from the date of first study treatment to the date of death or withdrawal from study, whichever comes first. The percentage of patients alive at 6 months, 12 months, and 24 months will be reported. All patients who receive at least one dose of nivolumab will be included in the secondary analyses of OS.

Outcome measures

Measure	Nivolumab + Ipilimumab n=19 Participants Nivolumab and ipilimumab combination will be administered intravenously until disease progression or intolerable toxicity. Nivolumab: Given at 240mg over 30 minutes (-5 / +15 minutes) every 2 weeks starting with Cycle 1 Day 1 for the first 16 weeks (1 cycle = 12 weeks). Starting with Cycle 2 Day 29, nivolumab will be given at 480mg IV over 60 minutes (-10 / +15 minutes) every 4 weeks. Ipilimumab: Given at 1mg/Kg every 6 weeks starting with Cycle 1 Day 1 over approximately 90 minutes (-5 / +15 minutes). On days when both nivolumab and ipilimumab are administered, nivolumab should be given first, followed by ipilimumab about 30 minutes after completion of nivolumab. Patients will be assessed for response every 12 weeks (±7 days).
Overall Survival (OS) Overall Survival at 6 months	89.47 percentage of participants Interval 76.69 to 100.0
Overall Survival (OS) Overall Survival at 12 months	73.68 percentage of participants Interval 56.32 to 96.4

SECONDARY outcome

Timeframe: Up to 30 days after discontinuation, where range of cycles attempted was 1-11, where 1 Cycle = 84 days/12 weeks

Toxicity, both frequency and severity, will continue to be measured by monitoring the occurrence of adverse events. Adverse events will be defined as those included in CTCAE v 4.03. AEs that were determined to be at least possibly related to study drug and graded 3, 4, 5 are included here. Grade 1 (mild): the event causes discomfort without disruption of normal daily activities. Grade 2 (moderate): the event causes discomfort that affects normal daily activities. Grade 3 (severe): the event makes the patient unable to perform normal daily activities or significantly affects his/her clinical status. Grade 4 (Life-threatening): the patient was at risk of death at the time of the event. Grade 5 (fatal): the event caused death.

Outcome measures

Measure	Nivolumab + Ipilimumab n=24 Participants Nivolumab and ipilimumab combination will be administered intravenously until disease progression or intolerable toxicity. Nivolumab: Given at 240mg over 30 minutes (-5 / +15 minutes) every 2 weeks starting with Cycle 1 Day 1 for the first 16 weeks (1 cycle = 12 weeks). Starting with Cycle 2 Day 29, nivolumab will be given at 480mg IV over 60 minutes (-10 / +15 minutes) every 4 weeks. Ipilimumab: Given at 1mg/Kg every 6 weeks starting with Cycle 1 Day 1 over approximately 90 minutes (-5 / +15 minutes). On days when both nivolumab and ipilimumab are administered, nivolumab should be given first, followed by ipilimumab about 30 minutes after completion of nivolumab. Patients will be assessed for response every 12 weeks (±7 days).
Number of Adverse Events Possibly Related to Study Drugs Graded 3, 4, and 5 Fatigue	1 Participants
Number of Adverse Events Possibly Related to Study Drugs Graded 3, 4, and 5 Lymphocyte Count Decreased	4 Participants
Number of Adverse Events Possibly Related to Study Drugs Graded 3, 4, and 5 Anemia	2 Participants
Number of Adverse Events Possibly Related to Study Drugs Graded 3, 4, and 5 Aspartate Aminotransferase increased	1 Participants
Number of Adverse Events Possibly Related to Study Drugs Graded 3, 4, and 5 Diarrhea	1 Participants
Number of Adverse Events Possibly Related to Study Drugs Graded 3, 4, and 5 Anorexia	1 Participants
Number of Adverse Events Possibly Related to Study Drugs Graded 3, 4, and 5 Alanine Aminotransferase Increased	1 Participants
Number of Adverse Events Possibly Related to Study Drugs Graded 3, 4, and 5 Weight Loss	1 Participants
Number of Adverse Events Possibly Related to Study Drugs Graded 3, 4, and 5 Adrenal Insufficiency	1 Participants
Number of Adverse Events Possibly Related to Study Drugs Graded 3, 4, and 5 Rash maculo-papular	1 Participants
Number of Adverse Events Possibly Related to Study Drugs Graded 3, 4, and 5 Alkaline Phosphatase Increased	1 Participants
Number of Adverse Events Possibly Related to Study Drugs Graded 3, 4, and 5 Colitis	1 Participants
Number of Adverse Events Possibly Related to Study Drugs Graded 3, 4, and 5 Mucositis oral	1 Participants
Number of Adverse Events Possibly Related to Study Drugs Graded 3, 4, and 5 Hypokalemia	1 Participants
Number of Adverse Events Possibly Related to Study Drugs Graded 3, 4, and 5 Hypophosphatemia	1 Participants
Number of Adverse Events Possibly Related to Study Drugs Graded 3, 4, and 5 Serum Amylase Increased	1 Participants

Adverse Events

Nivolumab + Ipilimumab

Serious events: 16 serious events

Other events: 24 other events

Deaths: 11 deaths

Serious adverse events

Measure	Nivolumab + Ipilimumab n=24 participants at risk；n=25 participants at risk Nivolumab and ipilimumab combination will be administered intravenously until disease progression or intolerable toxicity. Nivolumab: Given at 240mg over 30 minutes (-5 / +15 minutes) every 2 weeks starting with Cycle 1 Day 1 for the first 16 weeks (1 cycle = 12 weeks). Starting with Cycle 2 Day 29, nivolumab will be given at 480mg IV over 60 minutes (-10 / +15 minutes) every 4 weeks. Ipilimumab: Given at 1mg/Kg every 6 weeks starting with Cycle 1 Day 1 over approximately 90 minutes (-5 / +15 minutes). On days when both nivolumab and ipilimumab are administered, nivolumab should be given first, followed by ipilimumab about 30 minutes after completion of nivolumab. Patients will be assessed for response every 12 weeks (±7 days).
Injury, poisoning and procedural complications Spinal fracture	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Gastrointestinal disorders ascites	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
General disorders fever	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Infections and infestations sinusitis	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Investigations Alanine aminotransferase increased	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Musculoskeletal and connective tissue disorders Neck pain	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Gastrointestinal disorders nausea	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Gastrointestinal disorders Colitis	8.0% 2/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Vascular disorders Thromboembolic event	8.0% 2/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Renal and urinary disorders acute kidney injury	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Metabolism and nutrition disorders Hypokalemia	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Musculoskeletal and connective tissue disorders Pain Right Lower Limb	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Endocrine disorders Adrenal Insufficiency	8.0% 2/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenoid Cystic Carcinoma	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Metabolism and nutrition disorders anorexia	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Injury, poisoning and procedural complications Port Malfunction	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Gastrointestinal disorders Viral Gastroenteritis	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Psychiatric disorders confusion	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Nervous system disorders Cognitive Disturbance	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
General disorders Non-Cardiac Chest Pain	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Psychiatric disorders Anxiety	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Gastrointestinal disorders Abdominal Pain	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Infections and infestations sepsis	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Disease Progression	12.0% 3/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Nervous system disorders headache	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Skin and subcutaneous tissue disorders Left Jaw Cellulitis	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Nervous system disorders seizure	4.0% 1/25 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.

Other adverse events

Measure	Nivolumab + Ipilimumab n=24 participants at risk；n=25 participants at risk Nivolumab and ipilimumab combination will be administered intravenously until disease progression or intolerable toxicity. Nivolumab: Given at 240mg over 30 minutes (-5 / +15 minutes) every 2 weeks starting with Cycle 1 Day 1 for the first 16 weeks (1 cycle = 12 weeks). Starting with Cycle 2 Day 29, nivolumab will be given at 480mg IV over 60 minutes (-10 / +15 minutes) every 4 weeks. Ipilimumab: Given at 1mg/Kg every 6 weeks starting with Cycle 1 Day 1 over approximately 90 minutes (-5 / +15 minutes). On days when both nivolumab and ipilimumab are administered, nivolumab should be given first, followed by ipilimumab about 30 minutes after completion of nivolumab. Patients will be assessed for response every 12 weeks (±7 days).
Gastrointestinal disorders Abdominal pain	12.5% 3/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Endocrine disorders Adrenal insufficiency	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Investigations Alanine aminotransferase increased	25.0% 6/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Investigations Alkaline phosphatase increased	41.7% 10/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Skin and subcutaneous tissue disorders Alopecia	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Nervous system disorders Amnesia	8.3% 2/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Blood and lymphatic system disorders Anemia	62.5% 15/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Eye disorders Anisocoria	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Metabolism and nutrition disorders Anorexia	29.2% 7/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Psychiatric disorders Anxiety	12.5% 3/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Musculoskeletal and connective tissue disorders Arthralgia	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Musculoskeletal and connective tissue disorders Arthritis	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Investigations Aspartate aminotransferase increased	54.2% 13/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Musculoskeletal and connective tissue disorders Back pain	12.5% 3/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Nervous system disorders bilateral temporal bulging	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Investigations Blood bilirubin increased	25.0% 6/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Musculoskeletal and connective tissue disorders Bone pain	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
General disorders Cachexia	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Musculoskeletal and connective tissue disorders Chest wall pain	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
General disorders Chills	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
General disorders Chronic erythematous rash	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Gastrointestinal disorders Colitis	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Psychiatric disorders Confusion	8.3% 2/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Gastrointestinal disorders Constipation	33.3% 8/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Respiratory, thoracic and mediastinal disorders Cough	37.5% 9/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Investigations Creatinine increased	16.7% 4/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Metabolism and nutrition disorders Dehydration	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Injury, poisoning and procedural complications Dermatitis radiation	8.3% 2/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Skin and subcutaneous tissue disorders desquamation	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
General disorders Diaphoresis	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Gastrointestinal disorders Diarrhea	25.0% 6/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Gastrointestinal disorders Dry mouth	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Nervous system disorders Dysgeusia	8.3% 2/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Gastrointestinal disorders Dyspepsia	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Gastrointestinal disorders Dysphagia	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Respiratory, thoracic and mediastinal disorders Dyspnea	37.5% 9/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Ear and labyrinth disorders Ear pain	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
General disorders Edema face	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
General disorders Edema limbs	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
General disorders edema of c-spine	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Gastrointestinal disorders Enteritis	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Gastrointestinal disorders Enterocolitis	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Gastrointestinal disorders Epigastric burning	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Skin and subcutaneous tissue disorders erythema	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Respiratory, thoracic and mediastinal disorders erythema in throat	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Injury, poisoning and procedural complications Fall	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
General disorders Fatigue	50.0% 12/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Investigations Fibrinogen decreased	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Musculoskeletal and connective tissue disorders Flank pain	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
General disorders Flu like symptoms	8.3% 2/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Vascular disorders Flushing	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
General disorders Gait disturbance	8.3% 2/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Gastrointestinal disorders Gastroesophageal reflux disease	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Gastrointestinal disorders Gastroparesis	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Nervous system disorders Headache	16.7% 4/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Ear and labyrinth disorders Hearing impaired	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Renal and urinary disorders Hematuria	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Respiratory, thoracic and mediastinal disorders Hiccups	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Metabolism and nutrition disorders Hypercalcemia	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Metabolism and nutrition disorders Hyperglycemia	25.0% 6/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Metabolism and nutrition disorders Hyperkalemia	8.3% 2/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Vascular disorders Hypertension	83.3% 20/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Endocrine disorders Hyperthyroidism	25.0% 6/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Metabolism and nutrition disorders Hypoalbuminemia	50.0% 12/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Metabolism and nutrition disorders Hypocalcemia	20.8% 5/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Metabolism and nutrition disorders Hypoglycemia	8.3% 2/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Metabolism and nutrition disorders Hypokalemia	20.8% 5/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Metabolism and nutrition disorders Hyponatremia	33.3% 8/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Musculoskeletal and connective tissue disorders Hypophonia	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Metabolism and nutrition disorders Hypophosphatemia	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Vascular disorders Hypotension	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Endocrine disorders Hypothyroidism	29.2% 7/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
General disorders Infusion related reaction	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Investigations INR increased	8.3% 2/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Psychiatric disorders Insomnia	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
General disorders Left facial droop	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
General disorders Left facial paralysis	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Investigations Lipase increased	8.3% 2/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Investigations Lymphocyte count decreased	70.8% 17/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Gastrointestinal disorders Mucositis oral	8.3% 2/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Musculoskeletal and connective tissue disorders Muscle weakness right-sided	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Musculoskeletal and connective tissue disorders Myalgia	12.5% 3/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Respiratory, thoracic and mediastinal disorders Nasal congestion	12.5% 3/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Gastrointestinal disorders Nausea	37.5% 9/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
General disorders Non-cardiac chest pain	8.3% 2/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Musculoskeletal and connective tissue disorders Numbness/ pain forearm	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
General disorders Numbness/ tingling of the arm	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
General disorders Pain	8.3% 2/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Musculoskeletal and connective tissue disorders Pain in extremity	16.7% 4/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Investigations Platelet count decreased	12.5% 3/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Respiratory, thoracic and mediastinal disorders Pneumonia	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Respiratory, thoracic and mediastinal disorders Postnasal drip	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Nervous system disorders Presyncope	8.3% 2/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Respiratory, thoracic and mediastinal disorders Productive cough	12.5% 3/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Skin and subcutaneous tissue disorders Pruritus	16.7% 4/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Skin and subcutaneous tissue disorders Rash	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Skin and subcutaneous tissue disorders Rash maculo-papular	16.7% 4/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - NOS	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
General disorders Rhinorrhea	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
General disorders Right arm pain/ weakness	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Musculoskeletal and connective tissue disorders Right hand atrophy	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Eye disorders Right lower eyelid stye	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Investigations Sensation of Thick Tongue	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Investigations Serum amylase increased	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Cardiac disorders Sinus tachycardia	8.3% 2/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Infections and infestations Sinusitis	8.3% 2/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Infections and infestations Skin infection	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Nervous system disorders Somnolence	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Respiratory, thoracic and mediastinal disorders Sore throat	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Nervous system disorders Tremor	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Musculoskeletal and connective tissue disorders Trismus	8.3% 2/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Renal and urinary disorders Urinary frequency	12.5% 3/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Infections and infestations Urinary tract infection	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Investigations Urine output decreased	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Eye disorders Visual changes	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Gastrointestinal disorders Vomiting	12.5% 3/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Investigations Weight gain	12.5% 3/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Investigations Weight loss	45.8% 11/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.
Respiratory, thoracic and mediastinal disorders Wheezing	4.2% 1/24 • Adverse Events (AEs) were collected over a 3 year period, and is still continuing (2 patients still on treatment). For other AEs, each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. For Serious AEs, each patient was followed at time of consent and 100 days post last treatment. 1 Cycle = 84 days/12 weeks and the range of cycles attempted was 1-11. A patient who was registered and signed consent but did not initiate treatment is included as at risk for SAE but not at risk for other AEs. This patient never received treatment on study. All cause mortality and other adverse events are assessed from first dose of study treatment. Only patients that received at least 1 dose of study drug are included in all cause mortality and other adverse events. SAEs are assessed from patient signing consent.

Additional Information

Young Kwang Chae, MD, MPH, MBA

Northwestern University, Feinberg School of Medicine

Phone: 312-926-4248

Email: YCHAE@nm.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place