Trial Outcomes & Findings for Nivolumab and HPV-16 Vaccination in Patients With HPV-16 Positive Incurable Solid Tumors (NCT NCT02426892)

NCT ID: NCT02426892

Last Updated: 2023-04-18

Results Overview

ORR defined as sum of subjects with a complete response (CR) and partial response (PR) divided by number of evaluable subjects at 11 weeks from start of treatment. RECIST 1.1 criteria used for assessment. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 33 participants
• Primary outcome timeframe: From the time of the first protocol-specific intervention, every 6 weeks until progression, death, withdrawal of consent or study completion, an average of 4.5 years
• Results posted on: 2023-04-18

Participant Flow

33 participants were registered, 9 participants screen fail (not treated, not eligible or inevaluable)

Participant milestones

Measure	ISA101 Vaccine and Nivolumab Treatment with the ISA101 vaccine on days 1, 22 and 50. Nivolumab treatment IV starting day 8 of Cycle 1 and HPV-16 vaccination (ISA 101) administered subcutaneously at 100 mcg for a total of 3 doses at 3 to 4 weeks intervals starting on Day 1. Nivolumab administered intravenously at 3 mg/kg beginning on cycle 1 day 8 after the first vaccine dose and every two weeks there after until progression.
Overall Study STARTED	24
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	20

Reasons for withdrawal

Measure	ISA101 Vaccine and Nivolumab Treatment with the ISA101 vaccine on days 1, 22 and 50. Nivolumab treatment IV starting day 8 of Cycle 1 and HPV-16 vaccination (ISA 101) administered subcutaneously at 100 mcg for a total of 3 doses at 3 to 4 weeks intervals starting on Day 1. Nivolumab administered intravenously at 3 mg/kg beginning on cycle 1 day 8 after the first vaccine dose and every two weeks there after until progression.
Overall Study Adverse Event	2
Overall Study Lack of Efficacy	17
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Nivolumab and HPV-16 Vaccination in Patients With HPV-16 Positive Incurable Solid Tumors

Baseline characteristics by cohort

Measure	ISA101 Vaccine and Nivolumab n=33 Participants Treatment with the ISA101 vaccine on days 1, 22 and 50. Nivolumab treatment IV starting day 8 of Cycle 1 and HPV-16 vaccination (ISA 101) administered subcutaneously at 100 mcg for a total of 3 doses at 3 to 4 weeks intervals starting on Day 1. Nivolumab administered intravenously at 3 mg/kg beginning on cycle 1 day 8 after the first vaccine dose and every two weeks there after until progression.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	23 Participants n=5 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants
Race (NIH/OMB) White	25 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Region of Enrollment United States	33 participants n=5 Participants

PRIMARY outcome

Timeframe: From the time of the first protocol-specific intervention, every 6 weeks until progression, death, withdrawal of consent or study completion, an average of 4.5 years

ORR defined as sum of subjects with a complete response (CR) and partial response (PR) divided by number of evaluable subjects at 11 weeks from start of treatment. RECIST 1.1 criteria used for assessment. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Measure	ISA101 Vaccine and Nivolumab n=24 Participants Treatment with the ISA101 vaccine on days 1, 22 and 50. Nivolumab treatment IV starting day 8 of Cycle 1 and HPV-16 vaccination (ISA 101) administered subcutaneously at 100 mcg for a total of 3 doses at 3 to 4 weeks intervals starting on Day 1. Nivolumab administered intravenously at 3 mg/kg beginning on cycle 1 day 8 after the first vaccine dose and every two weeks there after until progression.
Number of Participants With Overall Response Rate (ORR) Complete Response (CR)	2 Participants
Number of Participants With Overall Response Rate (ORR) Partial Response (PR)	6 Participants

SECONDARY outcome

Timeframe: From the time of the first protocol-specific intervention, every 6 weeks until progression, death, withdrawal of consent or study completion, an average of 4.5 years.

PFS is defined as the time from first day of treatment to the date of the first documented tumor progression or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST V1.1). RECIST V1.1 defines progression as at least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm. Additionally, the appearance of one or more new lesions is also considered progression. Progression Free survival will be summarized using the method of Kaplan and Meier and Cox proportional hazards model.

Outcome measures

Measure

ISA101 Vaccine and Nivolumab n=24 Participants Treatment with the ISA101 vaccine on days 1, 22 and 50. Nivolumab treatment IV starting day 8 of Cycle 1 and HPV-16 vaccination (ISA 101) administered subcutaneously at 100 mcg for a total of 3 doses at 3 to 4 weeks intervals starting on Day 1. Nivolumab administered intravenously at 3 mg/kg beginning on cycle 1 day 8 after the first vaccine dose and every two weeks there after until progression.

Median Progression Free Survival (PFS)

2.66 months Interval 2.5 to 9.44

SECONDARY outcome

Timeframe: From the time of the first protocol-specific intervention, every 6 weeks until progression, death, withdrawal of consent or study completion, an average of 3 years.

PFS is defined as the time from first day of treatment to the date of the first documented tumor progression or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST V1.1). RECIST V1.1 defines progression as at least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm. Additionally, the appearance of one or more new lesions is also considered progression. Progression Free survival will be summarized using the method of Kaplan and Meier and Cox proportional hazards model.

Outcome measures

Measure	ISA101 Vaccine and Nivolumab n=24 Participants Treatment with the ISA101 vaccine on days 1, 22 and 50. Nivolumab treatment IV starting day 8 of Cycle 1 and HPV-16 vaccination (ISA 101) administered subcutaneously at 100 mcg for a total of 3 doses at 3 to 4 weeks intervals starting on Day 1. Nivolumab administered intravenously at 3 mg/kg beginning on cycle 1 day 8 after the first vaccine dose and every two weeks there after until progression.
Progression Free Survival (PFS) Rates at 2 and 3 Years 2 Years	12.5 months Interval 4.3 to 36.0
Progression Free Survival (PFS) Rates at 2 and 3 Years 3 Years	12.5 months Interval 4.3 to 36.0

SECONDARY outcome

Timeframe: 3 years

OS is defined as the time from treatment to the date of death, whichever comes first. Overall survival will be summarized using the method of Kaplan and Meier) and Cox proportional hazards model.

Outcome measures

Measure

ISA101 Vaccine and Nivolumab n=24 Participants Treatment with the ISA101 vaccine on days 1, 22 and 50. Nivolumab treatment IV starting day 8 of Cycle 1 and HPV-16 vaccination (ISA 101) administered subcutaneously at 100 mcg for a total of 3 doses at 3 to 4 weeks intervals starting on Day 1. Nivolumab administered intravenously at 3 mg/kg beginning on cycle 1 day 8 after the first vaccine dose and every two weeks there after until progression.

Median Overall Survival

15.3 months Interval 10.6 to 27.2

SECONDARY outcome

Timeframe: up to 3 years

OS is defined as the time from treatment to the date of death. Overall survival will be summarized using the method of Kaplan and Meier) and Cox proportional hazards model.

Outcome measures

Measure	ISA101 Vaccine and Nivolumab n=24 Participants Treatment with the ISA101 vaccine on days 1, 22 and 50. Nivolumab treatment IV starting day 8 of Cycle 1 and HPV-16 vaccination (ISA 101) administered subcutaneously at 100 mcg for a total of 3 doses at 3 to 4 weeks intervals starting on Day 1. Nivolumab administered intravenously at 3 mg/kg beginning on cycle 1 day 8 after the first vaccine dose and every two weeks there after until progression.
Overall Survival (OS) Rates at 2 and 3 Years 2 Years	33 months Interval 18.9 to 58.7
Overall Survival (OS) Rates at 2 and 3 Years 3 Years	12.5 months Interval 4.3 to 36.0

SECONDARY outcome

Timeframe: at baseline, and continuously throughout the study at the beginning of each subsequent cycle, up to 3 years

The safety and tolerability which will be measured by the incidence of adverse events, serious adverse events, deaths, and laboratory abnormalities. Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject or clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. Laboratory abnormalities are Any laboratory test result that is clinically significant or meets the definition of an SAE, laboratory abnormality that required the subject to have study drug discontinued or interrupted, laboratory abnormality that required the subject to receive specific corrective therapy. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Outcome measures

Measure	ISA101 Vaccine and Nivolumab n=24 Participants Treatment with the ISA101 vaccine on days 1, 22 and 50. Nivolumab treatment IV starting day 8 of Cycle 1 and HPV-16 vaccination (ISA 101) administered subcutaneously at 100 mcg for a total of 3 doses at 3 to 4 weeks intervals starting on Day 1. Nivolumab administered intravenously at 3 mg/kg beginning on cycle 1 day 8 after the first vaccine dose and every two weeks there after until progression.
Number of Participants With Adverse Events Adverse Events	23 Participants
Number of Participants With Adverse Events Serious Adverse Events	11 Participants
Number of Participants With Adverse Events Death	20 Participants
Number of Participants With Adverse Events Laboratory Abnormalities	3 Participants

Adverse Events

ISA101 Vaccine and Nivolumab

Serious events: 11 serious events

Other events: 23 other events

Deaths: 20 deaths

Serious adverse events

Measure	ISA101 Vaccine and Nivolumab n=24 participants at risk Treatment with the ISA101 vaccine on days 1, 22 and 50. Nivolumab treatment IV starting day 8 of Cycle 1 and HPV-16 vaccination (ISA 101) administered subcutaneously at 100 mcg for a total of 3 doses at 3 to 4 weeks intervals starting on Day 1. Nivolumab administered intravenously at 3 mg/kg beginning on cycle 1 day 8 after the first vaccine dose and every two weeks there after until progression.
Renal and urinary disorders Acute kidney injury	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Investigations lanine aminotransferase increased	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Blood and lymphatic system disorders Anemia	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Investigations Aspartate aminotransferase increased	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Respiratory, thoracic and mediastinal disorders Aspiration	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Gastrointestinal disorders Colonic obstruction	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Gastrointestinal disorders Dysphagia	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Respiratory, thoracic and mediastinal disorders Dyspnea	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Gastrointestinal disorders Gastroparesis	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Infections and infestations Infections and infestations - Other, specify	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Infections and infestations Lung infection	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Musculoskeletal and connective tissue disorders Neck pain	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Gastrointestinal disorders Oral hemorrhage	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Gastrointestinal disorders Pancreatitis	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Infections and infestations Soft tissue infection	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Nervous system disorders Syncope	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Vascular disorders Thromboembolic event	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.

Other adverse events

Measure	ISA101 Vaccine and Nivolumab n=24 participants at risk Treatment with the ISA101 vaccine on days 1, 22 and 50. Nivolumab treatment IV starting day 8 of Cycle 1 and HPV-16 vaccination (ISA 101) administered subcutaneously at 100 mcg for a total of 3 doses at 3 to 4 weeks intervals starting on Day 1. Nivolumab administered intravenously at 3 mg/kg beginning on cycle 1 day 8 after the first vaccine dose and every two weeks there after until progression.
Gastrointestinal disorders Abdominal pain	12.5% 3/24 • Number of events 3 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Investigations Activated partial thromboplastin time prolonged	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Renal and urinary disorders Acute kidney injury	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Investigations Alanine aminotransferase increased	12.5% 3/24 • Number of events 6 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Investigations Alkaline phosphatase increased	25.0% 6/24 • Number of events 8 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Immune system disorders Allergic reaction	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Blood and lymphatic system disorders Anemia	70.8% 17/24 • Number of events 44 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Metabolism and nutrition disorders Anorexia	25.0% 6/24 • Number of events 6 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Psychiatric disorders Anxiety	16.7% 4/24 • Number of events 4 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Musculoskeletal and connective tissue disorders Arthralgia	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Investigations Aspartate aminotransferase increased	20.8% 5/24 • Number of events 10 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Respiratory, thoracic and mediastinal disorders Aspiration	4.2% 1/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Musculoskeletal and connective tissue disorders Back pain	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Blood and lymphatic system disorders Blood and lymphatic system disorders - (bilirubin increased), specify	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Blood and lymphatic system disorders Blood bilirubin increased	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Investigations Blood bilirubin increased	29.2% 7/24 • Number of events 9 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Eye disorders Blurred vision	12.5% 3/24 • Number of events 3 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Musculoskeletal and connective tissue disorders Chest wall pain	4.2% 1/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
General disorders Chills	25.0% 6/24 • Number of events 7 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Investigations Cholesterol high	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Eye disorders Conjunctivitis	4.2% 1/24 • Number of events 3 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Gastrointestinal disorders Constipation	50.0% 12/24 • Number of events 14 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Respiratory, thoracic and mediastinal disorders Cough	54.2% 13/24 • Number of events 16 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Investigations Creatinine increased	12.5% 3/24 • Number of events 7 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Metabolism and nutrition disorders Dehydration	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Psychiatric disorders Depression	20.8% 5/24 • Number of events 5 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Gastrointestinal disorders Diarrhea	29.2% 7/24 • Number of events 10 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Nervous system disorders Dizziness	25.0% 6/24 • Number of events 7 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Gastrointestinal disorders Dry mouth	33.3% 8/24 • Number of events 8 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Skin and subcutaneous tissue disorders Dry skin	12.5% 3/24 • Number of events 3 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Gastrointestinal disorders Duodenal ulcer	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Nervous system disorders Dysarthria	8.3% 2/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Nervous system disorders Dysesthesia	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Nervous system disorders Dysgeusia	16.7% 4/24 • Number of events 4 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Gastrointestinal disorders Dysphagia	41.7% 10/24 • Number of events 12 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Respiratory, thoracic and mediastinal disorders Dyspnea	41.7% 10/24 • Number of events 16 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Ear and labyrinth disorders Ear pain	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
General disorders Edema face	20.8% 5/24 • Number of events 5 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
General disorders Edema limbs	8.3% 2/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Respiratory, thoracic and mediastinal disorders Epistaxis	8.3% 2/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Eye disorders Eye disorders - (Other), specify	8.3% 2/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Infections and infestations Eye infection	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
General disorders Facial pain	8.3% 2/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Injury, poisoning and procedural complications Fall	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
General disorders Fatigue	79.2% 19/24 • Number of events 25 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
General disorders Fever	37.5% 9/24 • Number of events 14 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Musculoskeletal and connective tissue disorders Flank pain	4.2% 1/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
General disorders Flu like symptoms	12.5% 3/24 • Number of events 3 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Gastrointestinal disorders Gastritis	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Gastrointestinal disorders Gastroesophageal reflux disease	8.3% 2/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
General disorders General disorders and administration site conditions - (diabetes type 2), specify	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
General disorders General disorders and administration site conditions - (sensory neuropathy), specify	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
General disorders General disorders and administration site conditions - (numbness), specify	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
General disorders General disorders and administration site conditions - (Other), specify	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
General disorders General disorders and administration site conditions - (left maxillary), specify	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
General disorders General disorders and administration site conditions - (right parotitis was given anitbiotic), speci	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
General disorders General disorders and administration site conditions - (possible related to nivolumab), specify - 10	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Musculoskeletal and connective tissue disorders Generalized muscle weakness - 10062572 / CTCAE4.03	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Nervous system disorders Headache	33.3% 8/24 • Number of events 9 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Ear and labyrinth disorders Hearing impaired	16.7% 4/24 • Number of events 4 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Gastrointestinal disorders Hemorrhoids	12.5% 3/24 • Number of events 3 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Respiratory, thoracic and mediastinal disorders Hoarseness	16.7% 4/24 • Number of events 4 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Vascular disorders Hot flashes	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Metabolism and nutrition disorders Hypercalcemia	12.5% 3/24 • Number of events 3 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Metabolism and nutrition disorders Hyperglycemia	33.3% 8/24 • Number of events 12 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Metabolism and nutrition disorders Hyperkalemia	12.5% 3/24 • Number of events 3 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Metabolism and nutrition disorders Hypernatremia	4.2% 1/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Vascular disorders Hypertension	29.2% 7/24 • Number of events 7 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Metabolism and nutrition disorders Hypoalbuminemia	16.7% 4/24 • Number of events 5 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Metabolism and nutrition disorders Hypocalcemia	8.3% 2/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Metabolism and nutrition disorders Hypokalemia	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Metabolism and nutrition disorders Hypomagnesemia	33.3% 8/24 • Number of events 17 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Metabolism and nutrition disorders Hyponatremia	8.3% 2/24 • Number of events 3 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Endocrine disorders Hypoparathyroidism	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Metabolism and nutrition disorders Hypophosphatemia	16.7% 4/24 • Number of events 5 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Endocrine disorders Hypothyroidism	29.2% 7/24 • Number of events 9 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Infections and infestations Infections and infestations - (possibly related to nivolumab MRSA and pneumonia), specify	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Infections and infestations Infections and infestations - (Cellulitis), specify	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Infections and infestations Infections and infestations - (Other), specify	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
General disorders Injection site reaction	8.3% 2/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Investigations INR increased	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Psychiatric disorders Insomnia	20.8% 5/24 • Number of events 5 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Investigations Investigations - (RELATED TO NIVO. INCREASE NEUTOROPHILE COUNT), specify	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Investigations Lipase increased	4.2% 1/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Infections and infestations Lung infection	4.2% 1/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Vascular disorders Lymphedema	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Investigations Lymphocyte count decreased	33.3% 8/24 • Number of events 8 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Nervous system disorders Memory impairment	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Metabolism and nutrition disorders Metabolism and nutrition disorders - (Possible related to Nivo), specify	4.2% 1/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Musculoskeletal and connective tissue disorders Muscle weakness right-sided	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Musculoskeletal and connective tissue disorders Muscle weakness upper limb	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Specify (not related to nivolumab)	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Musculoskeletal and connective tissue disorders Myalgia	16.7% 4/24 • Number of events 4 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Respiratory, thoracic and mediastinal disorders Nasal congestion	8.3% 2/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Gastrointestinal disorders Nausea	62.5% 15/24 • Number of events 22 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
General disorders Neck edema	4.2% 1/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Musculoskeletal and connective tissue disorders Neck pain	8.3% 2/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Gastrointestinal disorders Oral dysesthesia	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Gastrointestinal disorders Oral hemorrhage	4.2% 1/24 • Number of events 3 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Gastrointestinal disorders Oral pain	8.3% 2/24 • Number of events 3 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Infections and infestations Otitis media	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
General disorders Pain	54.2% 13/24 • Number of events 16 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Musculoskeletal and connective tissue disorders Pain in extremity	16.7% 4/24 • Number of events 5 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Gastrointestinal disorders Pancreatitis	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Nervous system disorders Paresthesia	8.3% 2/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Nervous system disorders Peripheral sensory neuropathy	12.5% 3/24 • Number of events 3 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Skin and subcutaneous tissue disorders Photosensitivity	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Investigations Platelet count decreased	4.2% 1/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Respiratory, thoracic and mediastinal disorders Pleural effusion	12.5% 3/24 • Number of events 3 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Skin and subcutaneous tissue disorders Pruritus	16.7% 4/24 • Number of events 5 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Skin and subcutaneous tissue disorders Rash maculo-papular	20.8% 5/24 • Number of events 6 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Renal and urinary disorders Renal and urinary disorders - (nocturia), specify	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Renal and urinary disorders Renal and urinary disorders - (unlikely related to Nivo), specify	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Renal and urinary disorders Renal and urinary disorders - (Other), specify	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - (right vocal cord paralysis), specify	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - (secretions in the larynx/hypopharynx), specify	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Eye disorders Scleral disorder	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Investigations Serum amylase increased	4.2% 1/24 • Number of events 4 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Infections and infestations Sinusitis	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - (shingles), specify	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - (lump at vaccine injection site related to vaccine), specif	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Skin and subcutaneous tissue disorders Skin induration	16.7% 4/24 • Number of events 5 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Infections and infestations Skin infection	4.2% 1/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Respiratory, thoracic and mediastinal disorders Sleep apnea	8.3% 2/24 • Number of events 2 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Nervous system disorders Syncope	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Musculoskeletal and connective tissue disorders Trismus	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Renal and urinary disorders Urinary retention	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Infections and infestations Urinary tract infection	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Renal and urinary disorders Urinary urgency	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Gastrointestinal disorders Vomiting	25.0% 6/24 • Number of events 10 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Eye disorders Watering eyes	4.2% 1/24 • Number of events 1 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Investigations Weight loss	29.2% 7/24 • Number of events 7 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.
Investigations White blood cell decreased	12.5% 3/24 • Number of events 5 • Deaths, Serious Adverse Events and Other (Not Including Serious) Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 3 years. Number of participants affected 20, Number of Participants at Risk 24. 18 Patients affected died due to disease progression and all died greater than 30 days after last treatment on study. One died before starting treatment and one died at cycle 2 day 1 treatment, and both due to disease progression.

Additional Information

Dr. Renata Ferrarotto,MD, Associate Professor, Thoracic-Head & Neck Med Onc

UT MD Anderson Cancer Center

Phone: (713) 745-6774

Email: rferrarotto@mdanderson.org

Results disclosure agreements

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