Trial Outcomes & Findings for Phase I/II Eval Safety & Prelim Activity Nivolumab Comb W/Vorolanib Pts W/Refractory Thoracic Tumors (NCT NCT03583086)

NCT ID: NCT03583086

Last Updated: 2024-10-08

Results Overview

Maximum tolerated dose for vorolanib daily combined with 240mg nivolumab every 2 weeks based on 3+3 dose escalation design. When 2 out of 6 patients at one dose experienced dose limiting toxicity, lower dose will be used. We have specified the phase I and phase II populations as study arms; note outcome measures are then distinct for each arm, with the phase I arm intended to assess safety (MTD), and the phase 2 arm intended to assess efficacy, as typical for phase I-II studies. Thus, for each outcome, only the phase I cohort is included in the analysis population, or only the phase II cohort is including in the analysis population, as relevant to the outcome measure.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 88 participants
• Primary outcome timeframe: At 28 days
• Results posted on: 2024-10-08

Participant Flow

Participant milestones

Measure	Escalation Level 1 (Vorolanib 200 mg +Nivolumab 240mg) Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Escalation Level 2 (Vorolanib 300mg + Nivolumab 240mg) Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression.	Dose Expansion - Non Small-Cell-Lung Cancer Acquired Resistance Participants receive 200mg vorolanib PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Naive Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Primary Refractory Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Small Cell Lung Cancer - Progressed on Platinum-based Chemotherapy Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Thymic Carcinoma Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV
Overall Study STARTED	3	7	19	15	17	18	9
Overall Study COMPLETED	1	1	4	4	2	2	1
Overall Study NOT COMPLETED	2	6	15	11	15	16	8

Reasons for withdrawal

Measure	Escalation Level 1 (Vorolanib 200 mg +Nivolumab 240mg) Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Escalation Level 2 (Vorolanib 300mg + Nivolumab 240mg) Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression.	Dose Expansion - Non Small-Cell-Lung Cancer Acquired Resistance Participants receive 200mg vorolanib PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Naive Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Primary Refractory Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Small Cell Lung Cancer - Progressed on Platinum-based Chemotherapy Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Thymic Carcinoma Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV
Overall Study Death	2	6	12	10	14	14	4
Overall Study Withdrawal by Subject	0	0	1	0	0	0	1
Overall Study Refused follow-up	0	0	1	0	1	0	0
Overall Study Declining Performance Status	0	0	1	0	0	0	0
Overall Study Still on study	0	0	0	1	0	0	1
Overall Study Disease progression	0	0	0	0	0	0	1
Overall Study Undergoing radiation therapy	0	0	0	0	0	0	1
Overall Study Lost to Follow-up	0	0	0	0	0	1	0
Overall Study Adverse Event	0	0	0	0	0	1	0

Baseline Characteristics

Phase I/II Eval Safety & Prelim Activity Nivolumab Comb W/Vorolanib Pts W/Refractory Thoracic Tumors

Baseline characteristics by cohort

Measure	Escalation Level 1 (Vorolanib 200+Nivolumab 240mg) n=3 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Escalation Level 2 (Vorolanib 300+Nivolumab 240mg) n=7 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression.	Dose Expansion - Non Small-Cell-Lung Cancer Acquired Resistance n=19 Participants Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Naive n=15 Participants Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Primary Refractory n=17 Participants Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Small Cell Lung Cancer - Progressed on Platinum-based Chemotherapy n=18 Participants Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Thymic Carcinoma n=9 Participants Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Total n=88 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants	5 Participants n=4 Participants	8 Participants n=21 Participants	10 Participants n=10 Participants	6 Participants n=115 Participants	42 Participants n=24 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants	10 Participants n=4 Participants	9 Participants n=21 Participants	8 Participants n=10 Participants	3 Participants n=115 Participants	46 Participants n=24 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	9 Participants n=4 Participants	9 Participants n=21 Participants	7 Participants n=10 Participants	2 Participants n=115 Participants	38 Participants n=24 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	13 Participants n=5 Participants	6 Participants n=4 Participants	8 Participants n=21 Participants	11 Participants n=10 Participants	7 Participants n=115 Participants	50 Participants n=24 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants	3 Participants n=24 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants	15 Participants n=4 Participants	12 Participants n=21 Participants	16 Participants n=10 Participants	8 Participants n=115 Participants	77 Participants n=24 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	5 Participants n=21 Participants	2 Participants n=10 Participants	0 Participants n=115 Participants	8 Participants n=24 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	2 Participants n=115 Participants	3 Participants n=24 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=10 Participants	1 Participants n=115 Participants	9 Participants n=24 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	7 Participants n=7 Participants	17 Participants n=5 Participants	10 Participants n=4 Participants	13 Participants n=21 Participants	15 Participants n=10 Participants	5 Participants n=115 Participants	70 Participants n=24 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants	1 Participants n=10 Participants	1 Participants n=115 Participants	6 Participants n=24 Participants
Region of Enrollment United States	3 participants n=5 Participants	7 participants n=7 Participants	19 participants n=5 Participants	15 participants n=4 Participants	17 participants n=21 Participants	18 participants n=10 Participants	9 participants n=115 Participants	88 participants n=24 Participants

PRIMARY outcome

Timeframe: At 28 days

Population: 8 patients with NSCLC and 2 patients with TC who received vorolanib orally daily and 240mg nivolumab every 2 weeks, and had assessable results.

Maximum tolerated dose for vorolanib daily combined with 240mg nivolumab every 2 weeks based on 3+3 dose escalation design. When 2 out of 6 patients at one dose experienced dose limiting toxicity, lower dose will be used.

We have specified the phase I and phase II populations as study arms; note outcome measures are then distinct for each arm, with the phase I arm intended to assess safety (MTD), and the phase 2 arm intended to assess efficacy, as typical for phase I-II studies. Thus, for each outcome, only the phase I cohort is included in the analysis population, or only the phase II cohort is including in the analysis population, as relevant to the outcome measure.

Outcome measures

Measure	Escalation n=10 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Naive Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Primary Refractory Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Small Cell Lung Cancer - Progressed on Platinum-based Chemotherapy Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Thymic Carcinoma Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV
Recommended Phase II Combination Dose in Phase I (Per Common Terminology Criteria for Adverse Events (CTCAE) Criteria Version 5)	200 mg	—	—	—	—

PRIMARY outcome

Timeframe: Up to 1 year.

Population: Patients who received 200mg vorolanib daily with 240mg nivolumab every two weeks and were available for measurement of tumor response.

Antitumor activity will be assessed by objective response rate. Best response is determined as complete response(CR), partial response(PR), stable disease and progressive disease based on per Response Evaluation Criteria in Solid Tumors (RECIST). Objective response rate is the percentage of patients who had a CR or PR.

We have specified the phase I and phase II populations as study arms; note outcome measures are then distinct for each arm, with the phase I arm intended to assess safety (MTD), and the phase 2 arm intended to assess efficacy, as typical for phase I-II studies. Thus, for each outcome, only the phase I cohort is included in the analysis population, or only the phase II cohort is including in the analysis population, as relevant to the outcome measure.

Outcome measures

Measure	Escalation n=18 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Naive n=15 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Primary Refractory n=17 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Small Cell Lung Cancer - Progressed on Platinum-based Chemotherapy n=18 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Thymic Carcinoma n=9 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV
Objective Response Rate in Phase II.	11.1 percentage of participants Interval 0.0 to 27.8	33 percentage of participants Interval 13.0 to 60.0	5.9 percentage of participants Interval 0.0 to 17.6	0 percentage of participants Interval 0.0 to 0.0	11 percentage of participants Interval 0.0 to 33.0

PRIMARY outcome

Timeframe: Up to 1 year.

Population: Patients who received 200mg vorolanib daily with 240mg nivolumab every two weeks and were available for measurement of tumor response(progression).

Antitumor activity will be assessed by progression free survival. Progression is termined per Response Evaluation Criteria in Solid Tumors (RECIST). Progression free survival (PFS) is defined as time from on treatment to disease progression or death (whicever comes first). Those without progression and alive were censored at last follow up. Kaplan-meier method is used to estimate the median survival time.

We have specified the phase I and phase II populations as study arms; note outcome measures are then distinct for each arm, with the phase I arm intended to assess safety (MTD), and the phase 2 arm intended to assess efficacy, as typical for phase I-II studies. Thus, for each outcome, only the phase I cohort is included in the analysis population, or only the phase II cohort is including in the analysis population, as relevant to the outcome measure.

Outcome measures

Measure	Escalation n=18 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Naive n=15 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Primary Refractory n=17 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Small Cell Lung Cancer - Progressed on Platinum-based Chemotherapy n=18 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Thymic Carcinoma n=9 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV
Progression Free Survival in Phase II	1.97 months Interval 1.54 to 4.6	7.16 months Interval 1.38 to insufficient number of participants with events	3.22 months Interval 1.84 to 4.6	1.36 months Interval 0.92 to 1.81	9.1 months Interval 1.81 to insufficient number of participants with events

PRIMARY outcome

Timeframe: Up to 1 year

Population: Patients who received 200mg vorolanib daily with 240mg nivolumab every two weeks, were available for measurement of tumor response, and had partial or complete response. No patients in the "Dose Expansion - Small Cell Lung Cancer - Progressed on Platinum-based Chemotherapy" group had a partial or complete response.

Duration of best response among patients who responsed to the treatment. Best response per Response Evaluation Criteria in Solid Tumors (RECIST). The duration of response was estimated from the first date of best overall response of a complete (CR) or partial response (PR) to the date of disease progression or death, using the Kaplan-Meier method.

We have specified the phase I and phase II populations as study arms; note outcome measures are then distinct for each arm, with the phase I arm intended to assess safety (MTD), and the phase 2 arm intended to assess efficacy, as typical for phase I-II studies. Thus, for each outcome, only the phase I cohort is included in the analysis population, or only the phase II cohort is including in the analysis population, as relevant to the outcome measure.

Outcome measures

Measure	Escalation n=2 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Naive n=5 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Primary Refractory n=1 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Small Cell Lung Cancer - Progressed on Platinum-based Chemotherapy n=1 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Thymic Carcinoma Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV
Duration of Response in Phase II.	2.7 months Interval 2.1 to Not enough patients and events for estimating.	NA months Interval 9.1 to Not enough events for estimating.	12.8 months Not enough patients and events for estimating.	NA months Not enough patients and events for estimating.	—

PRIMARY outcome

Timeframe: Up to 1 year

Population: Patients who received 200mg vorolanib daily with 240mg nivolumab every two weeks and were available for measurement of tumor response.

Antitumor activity will be assessed by disease control rate. Best response (complete response,CR; partial response, PR;stable disease , SD; or progression,PD) per Response Evaluation Criteria in Solid Tumors (RECIST). Disease control rate is the percentage of patients who had a CR,PR or SD.

We have specified the phase I and phase II populations as study arms; note outcome measures are then distinct for each arm, with the phase I arm intended to assess safety (MTD), and the phase 2 arm intended to assess efficacy, as typical for phase I-II studies. Thus, for each outcome, only the phase I cohort is included in the analysis population, or only the phase II cohort is including in the analysis population, as relevant to the outcome measure.

Outcome measures

Measure	Escalation n=18 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Naive n=15 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Primary Refractory n=17 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Small Cell Lung Cancer - Progressed on Platinum-based Chemotherapy n=18 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Thymic Carcinoma n=9 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV
Disease Control Rate in Phase II. Best Response Per Response Evaluation Criteria in Solid Tumors (RECIST)	44.4 percentage of participants Interval 22.2 to 66.7	53.3 percentage of participants Interval 26.7 to 80.0	52.9 percentage of participants Interval 29.4 to 76.5	11.0 percentage of participants Interval 0.0 to 27.8	66.7 percentage of participants Interval 33.3 to 100.0

PRIMARY outcome

Timeframe: Up to 2 years.

Population: Patients who received 200mg vorolanib daily with 240mg nivolumab every two weeks and were available for measurement of survival.

Antitumor activity will be assessed by overall survival. Overall survial is defined as the time from on treatment to death. Those alive were censored at last follow up. Kaplan-meier method is used to estimate the median overall survival time.

We have specified the phase I and phase II populations as study arms; note outcome measures are then distinct for each arm, with the phase I arm intended to assess safety (MTD), and the phase 2 arm intended to assess efficacy, as typical for phase I-II studies. Thus, for each outcome, only the phase I cohort is included in the analysis population, or only the phase II cohort is including in the analysis population, as relevant to the outcome measure.

Outcome measures

Measure	Escalation n=18 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Naive n=15 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Primary Refractory n=17 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Small Cell Lung Cancer - Progressed on Platinum-based Chemotherapy n=18 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Thymic Carcinoma n=9 Participants Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV
Overall Survival in Phase II.	10.81 months Interval 4.6 to insufficient number of participants with events	NA months Interval 8.77 to insufficient number of participants with events	16.27 months Interval 5.98 to insufficient number of participants with events	4.5 months Interval 3.75 to insufficient number of participants with events	21.06 months Interval 13.54 to insufficient number of participants with events

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 1 year

Antitumor activity will be assessed by correlation between the biomarkers and clinical outcomes. This is a exploratory end point. To assess the effects of combinatorial treatment on specific pharmacodynamic and pharmacogenetic biomarkers, including but not limited to circulating levels of serum CSF1 and VEGF, protein expression using CyTOF, and multiplex immunofluorescence.

Outcome measures

Outcome data not reported

Adverse Events

Escalation Level 1 (Vorolanib 200+Nivolumab 240mg)

Serious events: 3 serious events

Other events: 3 other events

Deaths: 2 deaths

Escalation Level 2 (Vorolanib 300+Nivolumab 240mg)

Serious events: 6 serious events

Other events: 7 other events

Deaths: 6 deaths

Dose Expansion - Non Small-Cell-Lung Cancer Acquired Resistance

Serious events: 9 serious events

Other events: 19 other events

Deaths: 13 deaths

Dose Expansion - Non Small-Cell-Lung Cancer Naive

Serious events: 10 serious events

Other events: 15 other events

Deaths: 12 deaths

Dose Expansion - Non Small-Cell-Lung Cancer Primary Refractory

Serious events: 9 serious events

Other events: 17 other events

Deaths: 14 deaths

Dose Expansion - Small Cell Lung Cancer - Progressed on Platinum-based Chemotherapy

Serious events: 5 serious events

Other events: 18 other events

Deaths: 14 deaths

Dose Expansion - Thymic Carcinoma

Serious events: 6 serious events

Other events: 9 other events

Deaths: 4 deaths

Serious adverse events

Measure	Escalation Level 1 (Vorolanib 200+Nivolumab 240mg) n=3 participants at risk Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Escalation Level 2 (Vorolanib 300+Nivolumab 240mg) n=7 participants at risk Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression.	Dose Expansion - Non Small-Cell-Lung Cancer Acquired Resistance n=19 participants at risk Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Naive n=15 participants at risk Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Primary Refractory n=17 participants at risk Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Small Cell Lung Cancer - Progressed on Platinum-based Chemotherapy n=18 participants at risk Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Thymic Carcinoma n=9 participants at risk Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV
General disorders Edema	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Cellulitis	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Investigations Hypoxia	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Lung infection	66.7% 2/3 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	42.9% 3/7 • Number of events 5 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Respiratory failure	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Wound infection	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Paraspinal abscess	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Epidural abscess	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Osteomyelitis	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Pneumonia	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	10.5% 2/19 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Emphysema	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Port infection	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Diarrhea	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	28.6% 2/7 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Bacterremia	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Esophageal fistula	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Tumor pain	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Psychiatric disorders Altered mental state	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Chronic volume overload (administration site)	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Cardiac disorders Restrictive cardiomyopathy	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Metabolic alkalosis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Respiratory acidosis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thymic carcinoma	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	28.6% 2/7 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	10.5% 2/19 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 2/18 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non Small Cell Lung Cancer	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Tracheal stenosis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Volume depletion	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Sepsis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	10.5% 2/19 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Injury, poisoning and procedural complications Overdose	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Hip pain	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain metastasis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Fever	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Disease progression	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Cardiac disorders Sinus tachycardia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Vascular disorders Stroke	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Nervous system disorders Intracranial hemorrhage	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Cardiac disorders Hypertension	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Pleurex catheter infection	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Appendicitis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Abdominal pain	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Blood and lymphatic system disorders Febrile Neutropenia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Pericardial Effusion	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Exacerbation of COPD	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Injury, poisoning and procedural complications Fall	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Injury, poisoning and procedural complications Fractured ankle	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Chest pain	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Chills	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Immune system disorders Urinary tract infection	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Injury, poisoning and procedural complications Kidney injury	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Gallbladder pain	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Hepatobiliary disorders Calculus of Gallbladder	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Vascular disorders Chronic Venous Stasis ulcer	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Empyema	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Pleurx catheter infection	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Nervous system disorders Seizure	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Musculoskeletal and connective tissue disorders Muscle Weakness	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations COVID	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Nervous system disorders Peripheral Sensory Neuropathy	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Immune system disorders Guillain-Barre Syndrome	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Viral infection	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Enterocolitis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Nausea	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Vomitting	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Viral hepatitis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Investigations Alanine aminotransferase increased	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Surgical and medical procedures Thoracoscopy Pericaridal window	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Gastritis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Cholelithiasis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.
Musculoskeletal and connective tissue disorders Myositis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Death	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.

Other adverse events

Measure	Escalation Level 1 (Vorolanib 200+Nivolumab 240mg) n=3 participants at risk Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Escalation Level 2 (Vorolanib 300+Nivolumab 240mg) n=7 participants at risk Participants receive vorolanib PO QD on days 1-56 and nivolumab IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression.	Dose Expansion - Non Small-Cell-Lung Cancer Acquired Resistance n=19 participants at risk Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Naive n=15 participants at risk Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Non Small-Cell-Lung Cancer Primary Refractory n=17 participants at risk Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Small Cell Lung Cancer - Progressed on Platinum-based Chemotherapy n=18 participants at risk Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV	Dose Expansion - Thymic Carcinoma n=9 participants at risk Participants receive vorolanib 200mg PO QD on days 1-56 and nivolumab 240mg IV over 30 minutes every two weeks (i.e. on Days 1, 15, 29, and 43 of each 56-day cycle) for the first two treatment cycles. After which, the treatment schedule can change to every four weeks (i.e., on Days 1 and 29 of each 56-day cycle) if the patient is not exhibiting disease progression. Vorolanib: Given by mouth Nivolumab: Given by IV
Skin and subcutaneous tissue disorders Hair color change	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 2/18 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Skin ulceration	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Surgical and medical procedures Left hip total arthroplasty	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Vascular disorders Hypotension	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	10.5% 2/19 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Cardiac disorders Atrial fibrillation	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Ear and labyrinth disorders Hearing impaired	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Endocrine disorders Hyperthyroidism	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Flatulence	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Gastritis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Abdominal ascites	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Infected root canal	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Hypersomnia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Aches in legs	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Aches in neck	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Sinusitis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Vaginal yeast	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Left shoulder nodule	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Investigations Alkaline phosphatase increased	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Hyperkalemia	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Hyperglycemia	100.0% 3/3 • Number of events 5 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	26.7% 4/15 • Number of events 5 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Dehydration	33.3% 1/3 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	10.5% 2/19 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	33.3% 5/15 • Number of events 6 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Hyponatremia	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	16.7% 3/18 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	44.4% 4/9 • Number of events 7 • From initiation of protocol-indicated treatment up to approximately 67 months.
Musculoskeletal and connective tissue disorders Myalgia	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	33.3% 1/3 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	10.5% 2/19 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 2/18 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Musculoskeletal and connective tissue disorders Arthralgia	66.7% 2/3 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Musculoskeletal and connective tissue disorders Back pain	66.7% 2/3 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.	28.6% 2/7 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	26.7% 4/15 • Number of events 5 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.8% 2/17 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	44.4% 4/9 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Pain	66.7% 2/3 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	23.5% 4/17 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 4/18 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Chest pain	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Fatigue	66.7% 2/3 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.	71.4% 5/7 • Number of events 6 • From initiation of protocol-indicated treatment up to approximately 67 months.	57.9% 11/19 • Number of events 12 • From initiation of protocol-indicated treatment up to approximately 67 months.	33.3% 5/15 • Number of events 8 • From initiation of protocol-indicated treatment up to approximately 67 months.	47.1% 8/17 • Number of events 12 • From initiation of protocol-indicated treatment up to approximately 67 months.	50.0% 9/18 • Number of events 9 • From initiation of protocol-indicated treatment up to approximately 67 months.	33.3% 3/9 • Number of events 6 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Limb edema	66.7% 2/3 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	20.0% 3/15 • Number of events 5 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 2/18 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Fever	66.7% 2/3 • Number of events 6 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	10.5% 2/19 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Malaise	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Wheezing	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	10.5% 2/19 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Productive cough	33.3% 1/3 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	10.5% 2/19 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	33.3% 3/9 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Pulminary embolism	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Radiation fibrosis	33.3% 1/3 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	10.5% 2/19 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Cough	66.7% 2/3 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	42.9% 3/7 • Number of events 6 • From initiation of protocol-indicated treatment up to approximately 67 months.	15.8% 3/19 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	100.0% 3/3 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	21.1% 4/19 • Number of events 5 • From initiation of protocol-indicated treatment up to approximately 67 months.	46.7% 7/15 • Number of events 8 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.8% 2/17 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Epistaxis	33.3% 1/3 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Upper Respiratory Infection	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Pleura effustion	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	10.5% 2/19 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 2/18 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders COPD	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Nasal congestion	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Injury, poisoning and procedural complications Wound on left heel post surgery	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Injury, poisoning and procedural complications Tripped	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Injury, poisoning and procedural complications Fall	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	28.6% 2/7 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Possible spider bite	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Allergies	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Sinus congestion	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Surgical and medical procedures Hernia surgery	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Eye disorders Ocular fungal infection	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Eye disorders Blepharitis	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Lung infection	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.8% 2/17 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	33.3% 3/9 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Seasonal allegies	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Renal and urinary disorders Urinary tract infection	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.
Vascular disorders Hypertenson	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	28.6% 2/7 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	21.1% 4/19 • Number of events 5 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	17.6% 3/17 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 2/18 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.
Ear and labyrinth disorders Hearing loss	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Rash acneiform	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.8% 2/17 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Skin infection	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Virus	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Anorexia	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	26.3% 5/19 • Number of events 7 • From initiation of protocol-indicated treatment up to approximately 67 months.	26.7% 4/15 • Number of events 5 • From initiation of protocol-indicated treatment up to approximately 67 months.	23.5% 4/17 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Sclerosis	33.3% 1/3 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Blood and lymphatic system disorders Anemia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	28.6% 2/7 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	33.3% 5/15 • Number of events 20 • From initiation of protocol-indicated treatment up to approximately 67 months.	17.6% 3/17 • Number of events 5 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 2/18 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	55.6% 5/9 • Number of events 7 • From initiation of protocol-indicated treatment up to approximately 67 months.
Cardiac disorders Constrictive cardiomyopathy	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	15.8% 3/19 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.8% 2/17 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 4/18 • Number of events 5 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Constipation	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	28.6% 2/7 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	10.5% 2/19 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.8% 2/17 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 2/18 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Diarrhea	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	28.6% 2/7 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.	26.3% 5/19 • Number of events 6 • From initiation of protocol-indicated treatment up to approximately 67 months.	46.7% 7/15 • Number of events 17 • From initiation of protocol-indicated treatment up to approximately 67 months.	29.4% 5/17 • Number of events 8 • From initiation of protocol-indicated treatment up to approximately 67 months.	16.7% 3/18 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 7 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Dry mouth	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	28.6% 2/7 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	20.0% 3/15 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Oral mucositis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Nausea	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	71.4% 5/7 • Number of events 8 • From initiation of protocol-indicated treatment up to approximately 67 months.	26.3% 5/19 • Number of events 5 • From initiation of protocol-indicated treatment up to approximately 67 months.	26.7% 4/15 • Number of events 9 • From initiation of protocol-indicated treatment up to approximately 67 months.	47.1% 8/17 • Number of events 10 • From initiation of protocol-indicated treatment up to approximately 67 months.	16.7% 3/18 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Vomiting	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	42.9% 3/7 • Number of events 8 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.8% 2/17 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Chills	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Face edema	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Flu-like symptoms	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Gait disturbance	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Localized edema	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Injury, poisoning and procedural complications Bruising	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.
Investigations Alanine aminotransferase increased	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	28.6% 2/7 • Number of events 5 • From initiation of protocol-indicated treatment up to approximately 67 months.	15.8% 3/19 • Number of events 6 • From initiation of protocol-indicated treatment up to approximately 67 months.	40.0% 6/15 • Number of events 12 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.8% 2/17 • Number of events 7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	55.6% 5/9 • Number of events 18 • From initiation of protocol-indicated treatment up to approximately 67 months.
Investigations Aspartate aminotransferase increased	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	42.9% 3/7 • Number of events 6 • From initiation of protocol-indicated treatment up to approximately 67 months.	10.5% 2/19 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.	40.0% 6/15 • Number of events 14 • From initiation of protocol-indicated treatment up to approximately 67 months.	17.6% 3/17 • Number of events 7 • From initiation of protocol-indicated treatment up to approximately 67 months.	16.7% 3/18 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.	77.8% 7/9 • Number of events 19 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Hypermagnesemia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	28.6% 2/7 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 2/18 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Nervous system disorders Myasthenia gravis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Nervous system disorders Headache	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.
Nervous system disorders Dizziness	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	21.1% 4/19 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	44.4% 4/9 • Number of events 6 • From initiation of protocol-indicated treatment up to approximately 67 months.
Nervous system disorders Dysgeusia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	10.5% 2/19 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.8% 2/17 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.
Psychiatric disorders Hallucinations	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Psychiatric disorders Anxiety	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	20.0% 3/15 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Psychiatric disorders Depression	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	10.5% 2/19 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Renal and urinary disorders Hematuria	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	17.6% 3/17 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Renal and urinary disorders Urine leukocyte esterase	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	28.6% 2/7 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	20.0% 3/15 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	28.6% 2/7 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	26.7% 4/15 • Number of events 5 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Sacral lesion	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	14.3% 1/7 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Blood and lymphatic system disorders Petechiae on fingers and chest	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Cardiac disorders Sinus tachycardia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Endocrine disorders Hypothyroidism	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Abdominal distension	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Bloating	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Oral pain	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Non-Cardiac Chest Pain	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 5 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Sepsis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	57.9% 11/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Bronchial infection	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Soft tissue infection	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Investigations Creatinine increased	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Investigations Lymphocyte count decreased	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Investigations Neutrophil count decreased	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	21.1% 4/19 • Number of events 14 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 12 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.8% 2/17 • Number of events 7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.
Investigations Platelet count decreased	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	10.5% 2/19 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 11 • From initiation of protocol-indicated treatment up to approximately 67 months.	17.6% 3/17 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.
Investigations Weight loss	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 8 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.8% 2/17 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 2/18 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Investigations White blood cell decreased	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	15.8% 3/19 • Number of events 10 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 16 • From initiation of protocol-indicated treatment up to approximately 67 months.	17.6% 3/17 • Number of events 15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.
Musculoskeletal and connective tissue disorders Chest wall pain	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Musculoskeletal and connective tissue disorders Gout	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Musculoskeletal and connective tissue disorders Spasms	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Nervous system disorders Syncope	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Nervous system disorders Presyncope	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Nervous system disorders Tremor	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Renal and urinary disorders Proteinuria	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	20.0% 3/15 • Number of events 6 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 2/18 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Renal and urinary disorders Elevated LFTs	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Renal and urinary disorders Urine discoloration	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	33.3% 3/9 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.
Renal and urinary disorders Dysuria	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Reproductive system and breast disorders Vaginal burning sensation	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Bronchial thickening	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Esophogeal stricture	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Penumonitis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	10.5% 2/19 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Peeling finger tips	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.3% 1/19 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Blood bilirubin increased	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.
Investigations Cholesterol high	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Investigations Elevated AST and ALT	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Investigations Transaminitis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Hypoalbuminemia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Glucose intolerence	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	16.7% 3/18 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Nervous system disorders Memory impairment	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 4 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Nervous system disorders Tremor in left hand	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Nervous system disorders Meningismus	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Nervous system disorders Movements involuntary	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Psychiatric disorders Insomnia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.8% 2/17 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.
Renal and urinary disorders Bladder spasm	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Renal and urinary disorders Urinary frequency	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Renal and urinary disorders Urinary tract pain	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Reproductive system and breast disorders Vaginal hemorrhage	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Sore throat	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Hoarseness	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	13.3% 2/15 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Left mid-back skin nodule	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Rash on back of head	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Small red pinpoint rash	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Yeast under both breasts	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Itching under both breasts	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Superficial wound on left back of calf	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Pulled right big toe nail off	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Surgical and medical procedures Pacemaker placement	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Surgical and medical procedures Port-a-cath placed in rt. internal jugular	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	6.7% 1/15 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Endocrine disorders Testosterone deficiency	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Eye disorders Ocular migrane	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Eye disorders Blurred vision	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Generalized edema	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Irritability	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Hepatobiliary disorders Hepatitis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Klebsilla Pneumoniae	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Diverticulitis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Decreased sodium	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Elevated bilirubin	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Bullous dermatitis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Photosensitivity	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Rash	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.9% 1/17 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Blood and lymphatic system disorders Leukopenia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Esophagitis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Restlessness	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Investigations Lipase increased	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Investigations Serum amylase increased	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Hypernatremia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Renal and urinary disorders Urinary urgency	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/9 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Hemoptysis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	5.6% 1/18 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.
Cardiac disorders Bradycardia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Cardiac disorders Aortic valve disease	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Endocrine disorders Adrenal insufficiency	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Endocrine disorders Elevated TSH	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Colitis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Colonic perforation	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Dysphagia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Hemorrhoids	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Hematochezia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Stool color change	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Aphthous ulcer	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Stomach flu	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Loose stool	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 3 • From initiation of protocol-indicated treatment up to approximately 67 months.
Gastrointestinal disorders Toothache	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Trunk edema	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Umbilical Hernia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
General disorders Common cold	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Hepatobiliary disorders Hepatic toxicity	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Bladder infection	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Thrush	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Infections and infestations Infection of the hypopharynx and larynx	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Investigations Weight gain	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Metabolism and nutrition disorders Increased appetite	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Musculoskeletal and connective tissue disorders Muscle cramp	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	22.2% 2/9 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.
Musculoskeletal and connective tissue disorders Right hand cramping	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Musculoskeletal and connective tissue disorders Left side rib pain	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.
Musculoskeletal and connective tissue disorders Shoulder pain	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Nervous system disorders Falling backward sensation	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Nervous system disorders Bilateral Hand Numbness/Tingling	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Nervous system disorders Head cold	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Nervous system disorders Paresthesia	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 2 • From initiation of protocol-indicated treatment up to approximately 67 months.
Reproductive system and breast disorders Vaginal inflammation	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Itchy throat	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Respiratory, thoracic and mediastinal disorders Rhinorrhea	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Rash, left buttocks	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Skin and subcutaneous tissue disorders Skin atrophy	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Vascular disorders Arterial thromboembolism	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Vascular disorders R supraclavicular fullness	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.
Vascular disorders Coronary vasospasm	0.00% 0/3 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/7 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/19 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/15 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/17 • From initiation of protocol-indicated treatment up to approximately 67 months.	0.00% 0/18 • From initiation of protocol-indicated treatment up to approximately 67 months.	11.1% 1/9 • Number of events 1 • From initiation of protocol-indicated treatment up to approximately 67 months.

Additional Information

Teresa Melton

Vanderbilt-Ingram Cancer Center

Phone: 6159367423

Email: teresa.melton@vumc.org

Results disclosure agreements

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