Trial Outcomes & Findings for Pembrolizumab and Pelareorep in Treating Patients With Advanced Pancreatic Cancer (NCT NCT03723915)

NCT ID: NCT03723915

Last Updated: 2022-10-05

Results Overview

To determine the overall response rate (ORR) by RECIST v 1.1 criteria for the combination of pembrolizumab with pelareorep. ORR is defined as the number of patients who have a complete or partial response to therapy (CR or PR). The Simon 2 stage design for this study requires 2 or more PR or CR in Stage 1 to continue accrual for Stage 2. Per RECIST v. 1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Patients who have taken one dose of either study drug, and completed the first on study scan (last week of Cycle 3) are evaluable. If a patient drops out of the study before the first scan, due to clinical progression, they are evaluable and will not be replaced.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 17 participants
• Primary outcome timeframe: Last week of Cycle 3 (1 Cycle = 21 days)
• Results posted on: 2022-10-05

Participant Flow

The study opened up to patient accrual on Nov. 2, 2018 with the first patient starting treatment Nov. 14, 2018 and an accrual goal of 34 patients. Stage 1 of the Simon 2 Stage design was completed on Jan 23, 2020, and the study was closed to accrual. The study did not meet the interim analysis criteria to continue to stage 2. Pharmacodynamic analysis is ongoing to identify biomarkers to predict response from therapy.

Participant milestones

Measure	Pembrolizumab 200 mg IV + Pelareorep 4.5x10^10 TCID_50 Pembrolizumab will be administered on Day 1 of each cycle at 200 mg IV over 30 minutes. In Cycle 1, Pelareorep will be administered at a dose of 4.5x10 \^10 TCID\_50 (Tissue Culture Infective Dose 50) over 60 minutes on Days 1, 2, 3 and 8. From Cycle 2 onwards, Pelareorep will be administered at a dose of 4.5x10\^10 TCID\_50 on Days 1 and 8. Pelareorep will be administered after completion of Pembrolizumab infusion on Day 1 of each cycle. Each cycle is 21 days (3 weeks). Up to 32 cycles of pembrolizumab and 24 months of Pelareorep (2 years) can be administered in the absence of progression, intolerable toxicity, and other discontinuation criteria (See protocol section 4.6).
Screening STARTED	17
Screening COMPLETED	15
Screening NOT COMPLETED	2
On Treatment STARTED	15
On Treatment Registered on Study	15
On Treatment Received First Dose of Study Drugs	13
On Treatment COMPLETED	13
On Treatment NOT COMPLETED	2
Survival Follow-up STARTED	13
Survival Follow-up COMPLETED	13
Survival Follow-up NOT COMPLETED	0

Reasons for withdrawal

Measure	Pembrolizumab 200 mg IV + Pelareorep 4.5x10^10 TCID_50 Pembrolizumab will be administered on Day 1 of each cycle at 200 mg IV over 30 minutes. In Cycle 1, Pelareorep will be administered at a dose of 4.5x10 \^10 TCID\_50 (Tissue Culture Infective Dose 50) over 60 minutes on Days 1, 2, 3 and 8. From Cycle 2 onwards, Pelareorep will be administered at a dose of 4.5x10\^10 TCID\_50 on Days 1 and 8. Pelareorep will be administered after completion of Pembrolizumab infusion on Day 1 of each cycle. Each cycle is 21 days (3 weeks). Up to 32 cycles of pembrolizumab and 24 months of Pelareorep (2 years) can be administered in the absence of progression, intolerable toxicity, and other discontinuation criteria (See protocol section 4.6).
Screening Failed to meet screening requirements.	2
On Treatment Failed to meet treatment requirements	2

Baseline Characteristics

Pembrolizumab and Pelareorep in Treating Patients With Advanced Pancreatic Cancer

Baseline characteristics by cohort

Measure	Pembrolizumab 200 mg IV + Pelareorep 4.5x10^10 TCID_50 n=13 Participants Pembrolizumab will be administered on Day 1 of each cycle at 200 mg IV over 30 minutes. In Cycle 1, Pelareorep will be administered at a dose of 4.5x10 \^10 TCID\_50 over 60 minutes on Days 1, 2, 3 and 8. From Cycle 2 onwards, Pelareorep will be administered at a dose of 4.5x10\^10 TCID\_50 on Days 1 and 8. Pelareorep will be administered after completion of Pembrolizumab infusion on Day 1 of each cycle. Each cycle is 21 days (3 weeks). Up to 32 cycles of pembrolizumab and 24 months of Pelareorep (2 years) can be administered in the absence of progression, intolerable toxicity, and other discontinuation criteria (See protocol section 4.6).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 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	1 Participants n=5 Participants
Race (NIH/OMB) White	9 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	13 participants n=5 Participants

PRIMARY outcome

Timeframe: Last week of Cycle 3 (1 Cycle = 21 days)

Population: Although 13 patients received treatment, 1 patient refused treatment after Cycle 1. Their response data was not available for evaluation.

To determine the overall response rate (ORR) by RECIST v 1.1 criteria for the combination of pembrolizumab with pelareorep. ORR is defined as the number of patients who have a complete or partial response to therapy (CR or PR). The Simon 2 stage design for this study requires 2 or more PR or CR in Stage 1 to continue accrual for Stage 2. Per RECIST v. 1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Patients who have taken one dose of either study drug, and completed the first on study scan (last week of Cycle 3) are evaluable. If a patient drops out of the study before the first scan, due to clinical progression, they are evaluable and will not be replaced.

Outcome measures

Measure	Pembrolizumab 200 mg IV + Pelareorep 4.5x10^10 TCID_50 n=12 Participants Pembrolizumab will be administered on Day 1 of each cycle at 200 mg IV over 30 minutes. In Cycle 1, Pelareorep will be administered at a dose of 4.5x10 \^10 TCID\_50 over 60 minutes on Days 1, 2, 3 and 8. From Cycle 2 onwards, Pelareorep will be administered at a dose of 4.5x10\^10 TCID\_50 on Days 1 and 8. Pelareorep will be administered after completion of Pembrolizumab infusion on Day 1 of each cycle. Each cycle is 21 days (3 weeks). Up to 32 cycles of pembrolizumab and 24 months of Pelareorep (2 years) can be administered in the absence of progression, intolerable toxicity, and other discontinuation criteria (See protocol section 4.6).
Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 Complete response	0 participants
Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 Partial response	1 participants

SECONDARY outcome

Timeframe: Up to 2 years

Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (including baseline if that is the smallest). In addition, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions is also considered progression. Kaplan-Meier curves will be used.

Outcome measures

Measure

Pembrolizumab 200 mg IV + Pelareorep 4.5x10^10 TCID_50 n=13 Participants Pembrolizumab will be administered on Day 1 of each cycle at 200 mg IV over 30 minutes. In Cycle 1, Pelareorep will be administered at a dose of 4.5x10 \^10 TCID\_50 over 60 minutes on Days 1, 2, 3 and 8. From Cycle 2 onwards, Pelareorep will be administered at a dose of 4.5x10\^10 TCID\_50 on Days 1 and 8. Pelareorep will be administered after completion of Pembrolizumab infusion on Day 1 of each cycle. Each cycle is 21 days (3 weeks). Up to 32 cycles of pembrolizumab and 24 months of Pelareorep (2 years) can be administered in the absence of progression, intolerable toxicity, and other discontinuation criteria (See protocol section 4.6).

Median Progression Free Survival (mPFS) by RECIST v 1.1

1.8727 months Interval 1.6099 to 7.1964

SECONDARY outcome

Timeframe: At 1 year

Measured from time of treatment initiation until death for any reason. Kaplan-Meier curves will be used.

Outcome measures

Measure

Pembrolizumab 200 mg IV + Pelareorep 4.5x10^10 TCID_50 n=13 Participants Pembrolizumab will be administered on Day 1 of each cycle at 200 mg IV over 30 minutes. In Cycle 1, Pelareorep will be administered at a dose of 4.5x10 \^10 TCID\_50 over 60 minutes on Days 1, 2, 3 and 8. From Cycle 2 onwards, Pelareorep will be administered at a dose of 4.5x10\^10 TCID\_50 on Days 1 and 8. Pelareorep will be administered after completion of Pembrolizumab infusion on Day 1 of each cycle. Each cycle is 21 days (3 weeks). Up to 32 cycles of pembrolizumab and 24 months of Pelareorep (2 years) can be administered in the absence of progression, intolerable toxicity, and other discontinuation criteria (See protocol section 4.6).

Overall Survival at One Year (12 Months)

7.69 percentage of patients Interval 1.17 to 50.57

SECONDARY outcome

Timeframe: At 2 years

Measured from time of treatment initiation until death for any reason. Kaplan-Meier curves will be used.

Outcome measures

Measure

Pembrolizumab 200 mg IV + Pelareorep 4.5x10^10 TCID_50 n=13 Participants Pembrolizumab will be administered on Day 1 of each cycle at 200 mg IV over 30 minutes. In Cycle 1, Pelareorep will be administered at a dose of 4.5x10 \^10 TCID\_50 over 60 minutes on Days 1, 2, 3 and 8. From Cycle 2 onwards, Pelareorep will be administered at a dose of 4.5x10\^10 TCID\_50 on Days 1 and 8. Pelareorep will be administered after completion of Pembrolizumab infusion on Day 1 of each cycle. Each cycle is 21 days (3 weeks). Up to 32 cycles of pembrolizumab and 24 months of Pelareorep (2 years) can be administered in the absence of progression, intolerable toxicity, and other discontinuation criteria (See protocol section 4.6).

Overall Survival (OS) at Two Years (24 Months)

7.69 percentage of patients Interval 1.17 to 50.57

SECONDARY outcome

Timeframe: Up to 2 years

Measured from time of treatment initiation until death from any cause. Kaplan-Meier curves will be used.

Outcome measures

Measure

Pembrolizumab 200 mg IV + Pelareorep 4.5x10^10 TCID_50 n=13 Participants Pembrolizumab will be administered on Day 1 of each cycle at 200 mg IV over 30 minutes. In Cycle 1, Pelareorep will be administered at a dose of 4.5x10 \^10 TCID\_50 over 60 minutes on Days 1, 2, 3 and 8. From Cycle 2 onwards, Pelareorep will be administered at a dose of 4.5x10\^10 TCID\_50 on Days 1 and 8. Pelareorep will be administered after completion of Pembrolizumab infusion on Day 1 of each cycle. Each cycle is 21 days (3 weeks). Up to 32 cycles of pembrolizumab and 24 months of Pelareorep (2 years) can be administered in the absence of progression, intolerable toxicity, and other discontinuation criteria (See protocol section 4.6).

Median Overall Survival (OS)

6.2094 months Interval 2.627 to 26.0849

SECONDARY outcome

Timeframe: Up to 30 days after last dose

Adverse events graded 3 using CTCAE 4.03 where:

Mild (grade 1): the event causes discomfort without disruption of normal daily activities.

Moderate (grade 2): the event causes discomfort that affects normal daily activities.

Severe (grade 3): the event makes the patient unable to perform normal daily activities or significantly affects his/her clinical status.

Life-threatening (grade 4): the patient was at risk of death at the time of the event.

Fatal (grade 5): the event caused death.

Outcome measures

Measure	Pembrolizumab 200 mg IV + Pelareorep 4.5x10^10 TCID_50 n=13 Participants Pembrolizumab will be administered on Day 1 of each cycle at 200 mg IV over 30 minutes. In Cycle 1, Pelareorep will be administered at a dose of 4.5x10 \^10 TCID\_50 over 60 minutes on Days 1, 2, 3 and 8. From Cycle 2 onwards, Pelareorep will be administered at a dose of 4.5x10\^10 TCID\_50 on Days 1 and 8. Pelareorep will be administered after completion of Pembrolizumab infusion on Day 1 of each cycle. Each cycle is 21 days (3 weeks). Up to 32 cycles of pembrolizumab and 24 months of Pelareorep (2 years) can be administered in the absence of progression, intolerable toxicity, and other discontinuation criteria (See protocol section 4.6).
Number of Patients With Adverse Events at Grade 3 Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 Fever	1 patients
Number of Patients With Adverse Events at Grade 3 Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 Vomiting	1 patients
Number of Patients With Adverse Events at Grade 3 Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 Nausea	1 patients
Number of Patients With Adverse Events at Grade 3 Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 Fatigue	2 patients
Number of Patients With Adverse Events at Grade 3 Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 Anemia	1 patients
Number of Patients With Adverse Events at Grade 3 Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 White blood cell decreased	1 patients
Number of Patients With Adverse Events at Grade 3 Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 Alkaline phosphatase increased	1 patients
Number of Patients With Adverse Events at Grade 3 Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 Lymphocyte count decreased	2 patients
Number of Patients With Adverse Events at Grade 3 Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 Neutrophil count decreased	1 patients
Number of Patients With Adverse Events at Grade 3 Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 Hyponatremia	2 patients

SECONDARY outcome

Timeframe: Up to 2 years

Will be assessed for change using paired statistical methods such as paired t-tests or signed rank tests.

Outcome measures

Outcome data not reported

Adverse Events

Pembrolizumab 200 mg IV + Pelareorep 4.5x10^10 TCID_50

Serious events: 10 serious events

Other events: 13 other events

Deaths: 11 deaths

Serious adverse events

Measure	Pembrolizumab 200 mg IV + Pelareorep 4.5x10^10 TCID_50 n=13 participants at risk；n=17 participants at risk Pembrolizumab will be administered on Day 1 of each cycle at 200 mg IV over 30 minutes. In Cycle 1, Pelareorep will be administered at a dose of 4.5x10 \^10 TCID\_50 over 60 minutes on Days 1, 2, 3 and 8. From Cycle 2 onwards, Pelareorep will be administered at a dose of 4.5x10\^10 TCID\_50 on Days 1 and 8. Pelareorep will be administered after completion of Pembrolizumab infusion on Day 1 of each cycle. Each cycle is 21 days (3 weeks). Up to 32 cycles of pembrolizumab and 24 months of Pelareorep (2 years) can be administered in the absence of progression, intolerable toxicity, and other discontinuation criteria (See protocol section 4.6).
Gastrointestinal disorders Abdominal Pain	11.8% 2/17 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Gastrointestinal disorders Obstruction Gastric	17.6% 3/17 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Investigations Blood bilirubin Increased	5.9% 1/17 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Injury, poisoning and procedural complications Vascular access Complication (RUE DVT)	5.9% 1/17 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Disease Progression	5.9% 1/17 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Hepatobiliary disorders Cholecystitis	5.9% 1/17 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified	17.6% 3/17 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Infections and infestations Endocarditis infective	5.9% 1/17 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Gastrointestinal disorders Constipation	5.9% 1/17 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	5.9% 1/17 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Gastrointestinal disorders Ascites	5.9% 1/17 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	5.9% 1/17 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Investigations Lymphocyte decreased	5.9% 1/17 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.

Other adverse events

Measure	Pembrolizumab 200 mg IV + Pelareorep 4.5x10^10 TCID_50 n=13 participants at risk；n=17 participants at risk Pembrolizumab will be administered on Day 1 of each cycle at 200 mg IV over 30 minutes. In Cycle 1, Pelareorep will be administered at a dose of 4.5x10 \^10 TCID\_50 over 60 minutes on Days 1, 2, 3 and 8. From Cycle 2 onwards, Pelareorep will be administered at a dose of 4.5x10\^10 TCID\_50 on Days 1 and 8. Pelareorep will be administered after completion of Pembrolizumab infusion on Day 1 of each cycle. Each cycle is 21 days (3 weeks). Up to 32 cycles of pembrolizumab and 24 months of Pelareorep (2 years) can be administered in the absence of progression, intolerable toxicity, and other discontinuation criteria (See protocol section 4.6).
Blood and lymphatic system disorders Anemia	69.2% 9/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Blood and lymphatic system disorders Leukocytosis	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Cardiac disorders Sinus bradycardia	23.1% 3/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Cardiac disorders Sinus tachycardia	46.2% 6/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Endocrine disorders Hypothyroidism	15.4% 2/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Gastrointestinal disorders Abdominal distension	23.1% 3/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Gastrointestinal disorders Abdominal pain	69.2% 9/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Gastrointestinal disorders Ascites	15.4% 2/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Gastrointestinal disorders Bloating	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Gastrointestinal disorders Constipation	38.5% 5/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Gastrointestinal disorders Diarrhea	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Gastrointestinal disorders Duodenal hemorrhage	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Gastrointestinal disorders Duodenal stenosis	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Gastrointestinal disorders Duodenal ulcer	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Gastrointestinal disorders Dyspepsia	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Gastrointestinal disorders Flatulence	15.4% 2/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Gastrointestinal disorders Gastric perforation	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Gastrointestinal disorders Nausea	61.5% 8/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Gastrointestinal disorders Obstruction gastric	23.1% 3/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Gastrointestinal disorders Vomiting	76.9% 10/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
General disorders Chills	92.3% 12/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
General disorders Edema limbs	30.8% 4/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
General disorders Fatigue	76.9% 10/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
General disorders Fever	92.3% 12/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
General disorders Non-cardiac chest pain	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
General disorders Pain	15.4% 2/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Hepatobiliary disorders Cholecystitis	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Hepatobiliary disorders Hepatobiliary disorders - Other, specify	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Infections and infestations Endocarditis infective	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Infections and infestations Infections and infestations - Other, specify	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Infections and infestations Sinusitis	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Infections and infestations Urinary tract infection	23.1% 3/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Injury, poisoning and procedural complications Bruising	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Injury, poisoning and procedural complications Vascular access complication	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Investigations Activated partial thromboplastin time prolonged	46.2% 6/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Investigations Alanine aminotransferase increased	30.8% 4/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Investigations Alkaline phosphatase increased	53.8% 7/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Investigations Aspartate aminotransferase increased	46.2% 6/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Investigations Blood bilirubin increased	38.5% 5/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Investigations Cardiac troponin I increased	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Investigations Fibrinogen decreased	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Investigations GGT increased	53.8% 7/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Investigations INR increased	23.1% 3/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Investigations Lymphocyte count decreased	61.5% 8/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Investigations Lymphocyte count increased	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Investigations Neutrophil count decreased	46.2% 6/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Investigations Platelet count decreased	46.2% 6/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Investigations Weight loss	15.4% 2/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Investigations White blood cell decreased	53.8% 7/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Metabolism and nutrition disorders Anorexia	61.5% 8/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Metabolism and nutrition disorders Dehydration	15.4% 2/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Metabolism and nutrition disorders Hyperglycemia	84.6% 11/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Metabolism and nutrition disorders Hypermagnesemia	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Metabolism and nutrition disorders Hypoalbuminemia	76.9% 10/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Metabolism and nutrition disorders Hypocalcemia	46.2% 6/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Metabolism and nutrition disorders Hypokalemia	46.2% 6/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Metabolism and nutrition disorders Hypomagnesemia	23.1% 3/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Metabolism and nutrition disorders Hyponatremia	53.8% 7/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Metabolism and nutrition disorders Hypophosphatemia	15.4% 2/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Musculoskeletal and connective tissue disorders Arthralgia	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Musculoskeletal and connective tissue disorders Back pain	38.5% 5/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Musculoskeletal and connective tissue disorders Flank pain	15.4% 2/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	15.4% 2/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	15.4% 2/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Musculoskeletal and connective tissue disorders Myalgia	15.4% 2/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Musculoskeletal and connective tissue disorders Neck pain	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Musculoskeletal and connective tissue disorders Pain in extremity	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	30.8% 4/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Nervous system disorders Depressed level of consciousness	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Nervous system disorders Dizziness	15.4% 2/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Nervous system disorders Headache	53.8% 7/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Nervous system disorders Presyncope	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Nervous system disorders Stroke	15.4% 2/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Nervous system disorders Tremor	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Psychiatric disorders Anxiety	15.4% 2/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Psychiatric disorders Confusion	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Psychiatric disorders Depression	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Psychiatric disorders Insomnia	15.4% 2/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Renal and urinary disorders Acute kidney injury	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Renal and urinary disorders Chronic kidney disease	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Renal and urinary disorders Hematuria	23.1% 3/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Renal and urinary disorders Proteinuria	38.5% 5/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Renal and urinary disorders Renal and urinary disorders - Other, specify	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Renal and urinary disorders Urinary frequency	15.4% 2/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Renal and urinary disorders Urine discoloration	38.5% 5/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Reproductive system and breast disorders Vaginal dryness	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Respiratory, thoracic and mediastinal disorders Cough	23.1% 3/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Respiratory, thoracic and mediastinal disorders Dyspnea	46.2% 6/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Respiratory, thoracic and mediastinal disorders Nasal congestion	15.4% 2/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Respiratory, thoracic and mediastinal disorders Pleural effusion	15.4% 2/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Respiratory, thoracic and mediastinal disorders Postnasal drip	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Skin and subcutaneous tissue disorders Hyperhidrosis	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Skin and subcutaneous tissue disorders Pruritus	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Skin and subcutaneous tissue disorders Rash acneiform	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Skin and subcutaneous tissue disorders Rash maculo-papular	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Vascular disorders Flushing	7.7% 1/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Vascular disorders Hypertension	100.0% 13/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.
Vascular disorders Hypotension	15.4% 2/13 • Adverse Events (AEs) were collected over a 2 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment, where 1 Cycle = 21 days the range of cycles attempted was 1-9. SAEs are collected from time of consent, and through 30 days post last dose of treatment (thus may include screen-fail patients who did not initiate treatment). All-Cause Mortality and Other Adverse Events are not monitored/assessed for screen-fail patients. Data collection for all-cause mortality and other adverse events begins at the time of treatment initiation.

Additional Information

Devalingam Mahalingam MD, PhD Associate Professor, Division of Hematology and Oncology

Northwestern University, Feinberg School of Medicine

Phone: 312-695-6929

Email: mahalingam@nm.org

Results disclosure agreements

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