Trial Outcomes & Findings for Sitravatinib and Nivolumab in Treating Patients With Advanced or Metastatic Kidney Cancer (NCT NCT03015740)

Last Updated: 2024-11-19

Results Overview

To determine the toxicities (defined as a grade 3 or 4 National Cancer Institute \[NCI\] non-hematologic or hematologic adverse event, within 12 weeks from treatment initiation),and efficacy (defined as achieving complete remission, partial remission, or stable disease within 6 weeks) of dosing.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

42 participants

Primary outcome timeframe

from enrollment up to 12 weeks for each dosing group

Results posted on

2024-11-19

Participant Flow

From April 2017 to February 2020, patients were recruited from the outpatient clinics for Genitourinary Medical Oncology at MD Anderson Cancer Center in Houston, Texas who have been diagnosed with cancer and currently undergoing outpatient treatment at the cancer center that are immunotherapy-naïve with ccRCC refractory to prior antiangiogenic therapies.

42 participants were randomized on trial

Participant milestones

Participant milestones
Measure	Received Sitravatinib 80 mg in Combination With Nivolumab combination of sitravatinib 80 MG and the anti-PD-1 agent nivolumab	Received Sitravatinib 120 mg in Combination With Nivolumab combination of sitravatinib 120 MG and the anti-PD-1 agent nivolumab	Received Sitravatinib 150 mg in Combination With Nivolumab combination of sitravatinib 150 MG and the anti-PD-1 agent nivolumab
Overall Study STARTED	15	24	3
Overall Study COMPLETED	9	19	3
Overall Study NOT COMPLETED	6	5	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Received Sitravatinib 80 mg in Combination With Nivolumab combination of sitravatinib 80 MG and the anti-PD-1 agent nivolumab	Received Sitravatinib 120 mg in Combination With Nivolumab combination of sitravatinib 120 MG and the anti-PD-1 agent nivolumab
Overall Study Adverse Event	1	0
Overall Study Death	3	5
Overall Study Withdrawal by Subject	2	0

Baseline Characteristics

Sitravatinib and Nivolumab in Treating Patients With Advanced or Metastatic Kidney Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Received Sitravatinib 80 mg in Combination With Nivolumab n=15 Participants combination of sitravatinib 80 MG and the anti-PD-1 agent nivolumab	Received Sitravatinib 120 mg in Combination With Nivolumab n=24 Participants combination of sitravatinib 120 MG and the anti-PD-1 agent nivolumab	Received Sitravatinib 150 mg in Combination With Nivolumab n=3 Participants combination of sitravatinib 150 MG and the anti-PD-1 agent nivolumab	Total n=42 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
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	10 Participants n=7 Participants	3 Participants n=5 Participants	17 Participants n=4 Participants
Age, Categorical >=65 years	11 Participants n=5 Participants	14 Participants n=7 Participants	0 Participants n=5 Participants	25 Participants n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	5 Participants n=7 Participants	0 Participants n=5 Participants	7 Participants n=4 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	19 Participants n=7 Participants	3 Participants n=5 Participants	35 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=5 Participants	23 Participants n=7 Participants	3 Participants n=5 Participants	37 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 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
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 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
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	21 Participants n=7 Participants	3 Participants n=5 Participants	36 Participants n=4 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
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Region of Enrollment United States	15 Participants n=5 Participants	24 Participants n=7 Participants	3 Participants n=5 Participants	42 Participants n=4 Participants

PRIMARY outcome

Timeframe: from enrollment up to 12 weeks for each dosing group

Population: A participant is considered enrolled when study medication is administered on Day 1

Outcome measures

Outcome measures
Measure	Received Sitravatinib 80 mg in Combination With Nivolumab n=15 Participants combination of sitravatinib and the anti-PD-1 agent nivolumab	Received Sitravatinib 120 mg in Combination With Nivolumab n=24 Participants combination of sitravatinib 120 MG and the anti-PD-1 agent nivolumab	Received Sitravatinib 150 mg in Combination With Nivolumab n=3 Participants combination of sitravatinib 150 MG and the anti-PD-1 agent nivolumab
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) DLTs within 12 weeks	4 participants	10 participants	3 participants
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) disease control at 6 weeks	13 participants	21 participants	3 participants

SECONDARY outcome

Timeframe: From enrollment to study completion, up to 5 years 4 months

To estimate the overall survival (OS) of patients with advanced clear cell renal cell cancer (RCC) treated with the combination of MGCD516 and nivolumab. The Secondary objective of the protocol is to capture combined results from all subjects who received treatment of the combination therapy. The intent was not to report results for each arm/group.

Outcome measures

Outcome measures
Measure	Received Sitravatinib 80 mg in Combination With Nivolumab n=42 Participants combination of sitravatinib and the anti-PD-1 agent nivolumab	Received Sitravatinib 120 mg in Combination With Nivolumab combination of sitravatinib 120 MG and the anti-PD-1 agent nivolumab	Received Sitravatinib 150 mg in Combination With Nivolumab combination of sitravatinib 150 MG and the anti-PD-1 agent nivolumab
Overall Survival (OS)	34 Participants	—	—

SECONDARY outcome

Timeframe: From enrollment to study completion, up to 5 years 4 months

To estimate the progression-free survival (PFS) times of patients with advanced clear cell renal cell cancer (RCC) treated with the combination of MGCD516 and nivolumab. : The Secondary objective of the protocol is to capture combined results from all subjects who received treatment of the combination therapy. The intent was not to report results for each arm/group.

Outcome measures

Outcome measures
Measure	Received Sitravatinib 80 mg in Combination With Nivolumab n=42 Participants combination of sitravatinib and the anti-PD-1 agent nivolumab	Received Sitravatinib 120 mg in Combination With Nivolumab combination of sitravatinib 120 MG and the anti-PD-1 agent nivolumab	Received Sitravatinib 150 mg in Combination With Nivolumab combination of sitravatinib 150 MG and the anti-PD-1 agent nivolumab
Progression-free Survival (PFS) Times	11.7 months Interval 8.2 to 16.6	—	—

SECONDARY outcome

Timeframe: From enrollment to study completion, up to 5 years 4 months

To estimate the objective response rates (ORR) of patients with advanced clear cell renal cell cancer (RCC) treated with the combination of MGCD516 and nivolumab. The Secondary objective of the protocol is to capture combined results from all subjects who received treatment of the combination therapy. The intent was not to report results for each arm/group.

Outcome measures

Outcome measures
Measure	Received Sitravatinib 80 mg in Combination With Nivolumab n=42 Participants combination of sitravatinib and the anti-PD-1 agent nivolumab	Received Sitravatinib 120 mg in Combination With Nivolumab combination of sitravatinib 120 MG and the anti-PD-1 agent nivolumab	Received Sitravatinib 150 mg in Combination With Nivolumab combination of sitravatinib 150 MG and the anti-PD-1 agent nivolumab
Objective Response Rates (ORR)	15 Participants	—	—

Adverse Events

Received Sitravatinib 80 mg in Combination With Nivolumab

Serious events: 8 serious events

Other events: 13 other events

Deaths: 3 deaths

Received Sitravatinib 120 mg in Combination With Nivolumab

Serious events: 14 serious events

Other events: 23 other events

Deaths: 5 deaths

Received Sitravatinib 150 mg in Combination With Nivolumab

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Pavlos Msaouel

M D Anderson Cancer Center

Phone: 713-563-4585

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Received Sitravatinib 80 mg in Combination With Nivolumab n=15 participants at risk combination of sitravatinib and the anti-PD-1 agent nivolumab	Received Sitravatinib 120 mg in Combination With Nivolumab n=24 participants at risk combination of sitravatinib 120 MG and the anti-PD-1 agent nivolumab	Received Sitravatinib 150 mg in Combination With Nivolumab n=3 participants at risk combination of sitravatinib 150 MG and the anti-PD-1 agent nivolumab
Gastrointestinal disorders abodominal pain	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Renal and urinary disorders acute kidney injury	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Blood and lymphatic system disorders anemia	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Infections and infestations appendicitus	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Respiratory, thoracic and mediastinal disorders bronchial obsturction	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Investigations creatinine increased	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Vascular disorders Hematoma	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Vascular disorders Hypertension	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Metabolism and nutrition disorders Hypocalcemia	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Metabolism and nutrition disorders Hypomagnesemia	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Respiratory, thoracic and mediastinal disorders Laryngeal hemorrhage	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Musculoskeletal and connective tissue disorders Myasthenia Gravis	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Cardiac disorders Myocardial infarction	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Gastrointestinal disorders Pancreatitis	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	8.3% 2/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Blood and lymphatic system disorders Portal vein thrombosis	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Infections and infestations Sepsis	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
General disorders Sudden death NOS	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Gastrointestinal disorders Surgical and medical procedures - Other, specify	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
General disorders Surgical and medical procedures - Other, specify	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	33.3% 1/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Renal and urinary disorders Surgical and medical procedures - Other, specify (nephrectomy in conjunction with hepatectomy)	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Vascular disorders Thromboembolic event	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	8.3% 2/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
General disorders Vertigo	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.

Other adverse events
Measure	Received Sitravatinib 80 mg in Combination With Nivolumab n=15 participants at risk combination of sitravatinib and the anti-PD-1 agent nivolumab	Received Sitravatinib 120 mg in Combination With Nivolumab n=24 participants at risk combination of sitravatinib 120 MG and the anti-PD-1 agent nivolumab	Received Sitravatinib 150 mg in Combination With Nivolumab n=3 participants at risk combination of sitravatinib 150 MG and the anti-PD-1 agent nivolumab
Gastrointestinal disorders Fecal incontinence	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	33.3% 1/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Gastrointestinal disorders Flatulence	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Gastrointestinal disorders Gastroesophageal reflux disease	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	13.3% 2/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	12.5% 3/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Blood and lymphatic system disorders Anemia	86.7% 13/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	87.5% 21/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	66.7% 2/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	12.5% 3/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Cardiac disorders Atrial fibrillation	13.3% 2/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Cardiac disorders Atrial flutter	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Cardiac disorders Cardiac disorders - Other, specify	13.3% 2/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Cardiac disorders Palpitations	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Cardiac disorders Sinus bradycardia	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	16.7% 4/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Cardiac disorders Sinus tachycardia	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	12.5% 3/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	33.3% 1/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Cardiac disorders Supraventricular tachycardia	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Ear and labyrinth disorders Ear and labyrinth disorders - Other, specify	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	66.7% 2/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Ear and labyrinth disorders Ear pain	13.3% 2/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	33.3% 1/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Ear and labyrinth disorders Hearing impaired	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Ear and labyrinth disorders Tinnitus	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Ear and labyrinth disorders Vertigo	13.3% 2/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Endocrine disorders Endocrine disorders - Other, specify	33.3% 5/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	25.0% 6/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	100.0% 3/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Endocrine disorders Hyperthyroidism	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	8.3% 2/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	33.3% 1/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Endocrine disorders Hypothyroidism	26.7% 4/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	58.3% 14/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	100.0% 3/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Eye disorders Blurred vision	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	25.0% 6/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	33.3% 1/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Eye disorders Conjunctivitis	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Eye disorders Eye disorders - Other, specify	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	8.3% 2/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Eye disorders Flashing lights	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	33.3% 1/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Eye disorders Watering eyes	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Gastrointestinal disorders Abdominal distension	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	12.5% 3/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Gastrointestinal disorders Abdominal pain	53.3% 8/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	37.5% 9/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	66.7% 2/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Gastrointestinal disorders Bloating	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Gastrointestinal disorders Constipation	53.3% 8/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	58.3% 14/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	33.3% 1/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Gastrointestinal disorders Diarrhea	73.3% 11/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	91.7% 22/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	100.0% 3/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Gastrointestinal disorders Dry mouth	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	33.3% 1/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Gastrointestinal disorders Dyspepsia	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Gastrointestinal disorders Dysphagia	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	8.3% 2/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Gastrointestinal disorders Hemorrhoids	0.00% 0/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	4.2% 1/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Gastrointestinal disorders Mucositis oral	40.0% 6/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Gastrointestinal disorders Nausea	53.3% 8/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	50.0% 12/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	66.7% 2/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Gastrointestinal disorders Oral dysesthesia	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.
Gastrointestinal disorders Oral pain	6.7% 1/15 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/24 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.	0.00% 0/3 • up to 5 years and 4 months Death A life-threatening adverse drug experience - any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred. It does not include experience that, had it occurred in a more severe form, might have caused death.