Trial Outcomes & Findings for An Exploratory Study of Pembrolizumab Plus Entinostat in Non-Inflamed Stage III/IV Melanoma (NCT NCT03765229)

NCT ID: NCT03765229

Last Updated: 2024-01-10

Results Overview

Number of subjects with conversion from non-inflamed Tumor-infiltrating lymphocyte / Tumor-associated lymphocyte (TIL/TAL) absent before treatment to TIL/TAL present after treatment was assessed by histopathologic analysis. Representative 5-micron thick formalin fixed paraffin embedded sections collected from baseline and on-treatment (entinostat-alone, day 21 of the trial) were stained with hematoxylin and eosin on day 21 (on-treatment biopsy).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 11 participants
• Primary outcome timeframe: 3 weeks after start of treatment
• Results posted on: 2024-01-10

Participant Flow

Subjects were enrolled in the study between 03/22/2019-05/24/2022, at one cancer center in the United States. A total of 11 participants consented, were found eligible and started to study. During the screening period, 22 subjects were consented to and 11 subjects did not enroll in the study since 10 of them were deemed not eligible and 1 subject expired.

Participant milestones

Measure	Single Arm: Entinostat + Pembrolizumab Subjects in this trial will be administered entinostat, 5mg PO, once weekly (D1, D8, D15 of a 21-day cycle) starting on day 1 of study treatment. Pembrolizumab, 200 mg will be administered intravenously (IV) every 3 weeks and initiated at cycle 2 after the mandatory research tumor biopsy in the end of cycle 1, beginning of cycle 2 (day 21±2 days),. Combination therapy with both agents will continue if subject is receiving clinical benefit from therapy for up to 27 weeks (8 cycles of combination therapy or approximately 6 months). Study therapy will be discontinued for intolerable toxicity, disease progression or for other reasons at the discretion of the investigator. Entinostat: Oral drug 5 mg taken once weekly for up to nine 3-week (21 day) cycles. Take on an empty stomach i.e., at least 2 hours after a meal and at least 1 hour before the next meal. On days when entinostat is administered on the same day as pembrolizumab, entinostat should be taken before the pembrolizumab infusion. Pembrolizumab: 200 mg IV starting on Day 22 (cycle 2, Day 1) given every 3 weeks for up to 8 cycles.
Overall Study STARTED	11
Overall Study COMPLETED	11
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

An Exploratory Study of Pembrolizumab Plus Entinostat in Non-Inflamed Stage III/IV Melanoma

Baseline characteristics by cohort

Measure	Single Arm: Entinostat + Pembrolizumab n=11 Participants Subjects in this trial will be administered entinostat, 5mg PO, once weekly (D1, D8, D15 of a 21-day cycle) starting on day 1 of study treatment. Pembrolizumab, 200 mg will be administered intravenously (IV) every 3 weeks and initiated at cycle 2 after the mandatory research tumor biopsy in the end of cycle 1, beginning of cycle 2 (day 21±2 days),. Combination therapy with both agents will continue if subject is receiving clinical benefit from therapy for up to 27 weeks (8 cycles of combination therapy or approximately 6 months). Study therapy will be discontinued for intolerable toxicity, disease progression or for other reasons at the discretion of the investigator. Entinostat: Oral drug 5 mg taken once weekly for up to nine 3-week (21 day) cycles. Take on an empty stomach i.e., at least 2 hours after a meal and at least 1 hour before the next meal. On days when entinostat is administered on the same day as pembrolizumab, entinostat should be taken before the pembrolizumab infusion. Pembrolizumab: 200 mg IV starting on Day 22 (cycle 2, Day 1) given every 3 weeks for up to 8 cycles.
Age, Continuous	58.36 years n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	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	0 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	1 Participants n=5 Participants
Region of Enrollment United States	11 participants n=5 Participants

PRIMARY outcome

Timeframe: 3 weeks after start of treatment

Number of subjects with conversion from non-inflamed Tumor-infiltrating lymphocyte / Tumor-associated lymphocyte (TIL/TAL) absent before treatment to TIL/TAL present after treatment was assessed by histopathologic analysis. Representative 5-micron thick formalin fixed paraffin embedded sections collected from baseline and on-treatment (entinostat-alone, day 21 of the trial) were stained with hematoxylin and eosin on day 21 (on-treatment biopsy).

Outcome measures

Measure	Single Arm: Entinostat + Pembrolizumab n=10 Participants Subjects in this trial will be administered entinostat, 5mg PO, once weekly (D1, D8, D15 of a 21-day cycle) starting on day 1 of study treatment. Pembrolizumab, 200 mg will be administered intravenously (IV) every 3 weeks and initiated at cycle 2 after the mandatory research tumor biopsy in the end of cycle 1, beginning of cycle 2 (day 21±2 days),. Combination therapy with both agents will continue if subject is receiving clinical benefit from therapy for up to 27 weeks (8 cycles of combination therapy or approximately 6 months). Study therapy will be discontinued for intolerable toxicity, disease progression or for other reasons at the discretion of the investigator. Entinostat: Oral drug 5 mg taken once weekly for up to nine 3-week (21 day) cycles. Take on an empty stomach i.e., at least 2 hours after a meal and at least 1 hour before the next meal. On days when entinostat is administered on the same day as pembrolizumab, entinostat should be taken before the pembrolizumab infusion. Pembrolizumab: 200 mg IV starting on Day 22 (cycle 2, Day 1) given every 3 weeks for up to 8 cycles.
Number of Conversions of Non-inflamed to Inflamed Melanoma Tumor-infiltrating lymphocyte increased	3 Participants
Number of Conversions of Non-inflamed to Inflamed Melanoma Tumor-infiltrating lymphocyte not increased	7 Participants

SECONDARY outcome

Timeframe: 9 weeks

Population: Subjects started to the study treatment and response evaluation per RECIST was completed.

Radiographic response will be measured by Response Evaluation Criteria In Solid Tumors (RECIST) Criteria for Complete Response (CR), disappearance of all target lesions or Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. The Overall Response rate will be the percentage of subjects with CR or PR at 9 weeks after the start of treatment.

Outcome measures

Measure	Single Arm: Entinostat + Pembrolizumab n=11 Participants Subjects in this trial will be administered entinostat, 5mg PO, once weekly (D1, D8, D15 of a 21-day cycle) starting on day 1 of study treatment. Pembrolizumab, 200 mg will be administered intravenously (IV) every 3 weeks and initiated at cycle 2 after the mandatory research tumor biopsy in the end of cycle 1, beginning of cycle 2 (day 21±2 days),. Combination therapy with both agents will continue if subject is receiving clinical benefit from therapy for up to 27 weeks (8 cycles of combination therapy or approximately 6 months). Study therapy will be discontinued for intolerable toxicity, disease progression or for other reasons at the discretion of the investigator. Entinostat: Oral drug 5 mg taken once weekly for up to nine 3-week (21 day) cycles. Take on an empty stomach i.e., at least 2 hours after a meal and at least 1 hour before the next meal. On days when entinostat is administered on the same day as pembrolizumab, entinostat should be taken before the pembrolizumab infusion. Pembrolizumab: 200 mg IV starting on Day 22 (cycle 2, Day 1) given every 3 weeks for up to 8 cycles.
Overall Response Rate Stable Disease or Progression	8 Participants
Overall Response Rate Complete Response or Partial Response	3 Participants

SECONDARY outcome

Timeframe: 6 months

Population: Subjects who started the study treatment and tumor response was evaluated, median follow-up time 14.3 (2.5-36.8) months.

Progression Free Survival is measured as the rate of patients who are progression-free from the date of enrollment on study to the date of documented progression per RECIST 1.1. criteria or death. Per RECIST 1.1, Progressive Disease (PD), is a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Measure	Single Arm: Entinostat + Pembrolizumab n=11 Participants Subjects in this trial will be administered entinostat, 5mg PO, once weekly (D1, D8, D15 of a 21-day cycle) starting on day 1 of study treatment. Pembrolizumab, 200 mg will be administered intravenously (IV) every 3 weeks and initiated at cycle 2 after the mandatory research tumor biopsy in the end of cycle 1, beginning of cycle 2 (day 21±2 days),. Combination therapy with both agents will continue if subject is receiving clinical benefit from therapy for up to 27 weeks (8 cycles of combination therapy or approximately 6 months). Study therapy will be discontinued for intolerable toxicity, disease progression or for other reasons at the discretion of the investigator. Entinostat: Oral drug 5 mg taken once weekly for up to nine 3-week (21 day) cycles. Take on an empty stomach i.e., at least 2 hours after a meal and at least 1 hour before the next meal. On days when entinostat is administered on the same day as pembrolizumab, entinostat should be taken before the pembrolizumab infusion. Pembrolizumab: 200 mg IV starting on Day 22 (cycle 2, Day 1) given every 3 weeks for up to 8 cycles.
Progression-Free Survival Alive with no evidence of disease	1 Participants
Progression-Free Survival Alive with disease	3 Participants
Progression-Free Survival Died from disease	7 Participants

SECONDARY outcome

Timeframe: 9 weeks

Type of AEs that occur in subjects enrolled who receive at least one dose of therapy will be reported based on the NCI Common Terminology Criteria for Adverse Events v5.0 (NCI-CTCAE v.5.0). The NCI-CTCAE is a descriptive terminology utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.

Outcome measures

Measure	Single Arm: Entinostat + Pembrolizumab n=11 Participants Subjects in this trial will be administered entinostat, 5mg PO, once weekly (D1, D8, D15 of a 21-day cycle) starting on day 1 of study treatment. Pembrolizumab, 200 mg will be administered intravenously (IV) every 3 weeks and initiated at cycle 2 after the mandatory research tumor biopsy in the end of cycle 1, beginning of cycle 2 (day 21±2 days),. Combination therapy with both agents will continue if subject is receiving clinical benefit from therapy for up to 27 weeks (8 cycles of combination therapy or approximately 6 months). Study therapy will be discontinued for intolerable toxicity, disease progression or for other reasons at the discretion of the investigator. Entinostat: Oral drug 5 mg taken once weekly for up to nine 3-week (21 day) cycles. Take on an empty stomach i.e., at least 2 hours after a meal and at least 1 hour before the next meal. On days when entinostat is administered on the same day as pembrolizumab, entinostat should be taken before the pembrolizumab infusion. Pembrolizumab: 200 mg IV starting on Day 22 (cycle 2, Day 1) given every 3 weeks for up to 8 cycles.
Number of Participant With Adverse Events During the Concurrent Pembrolizumab-entinostat Combination fatigue	11 Participants
Number of Participant With Adverse Events During the Concurrent Pembrolizumab-entinostat Combination nausea	6 Participants
Number of Participant With Adverse Events During the Concurrent Pembrolizumab-entinostat Combination vomiting	3 Participants
Number of Participant With Adverse Events During the Concurrent Pembrolizumab-entinostat Combination diarrhea	7 Participants
Number of Participant With Adverse Events During the Concurrent Pembrolizumab-entinostat Combination anorexia	3 Participants
Number of Participant With Adverse Events During the Concurrent Pembrolizumab-entinostat Combination musculoskeletal pain	5 Participants
Number of Participant With Adverse Events During the Concurrent Pembrolizumab-entinostat Combination cytopenia	2 Participants
Number of Participant With Adverse Events During the Concurrent Pembrolizumab-entinostat Combination anemia	8 Participants

Adverse Events

Single Arm: Entinostat + Pembrolizumab

Serious events: 5 serious events

Other events: 11 other events

Deaths: 7 deaths

Serious adverse events

Measure	Single Arm: Entinostat + Pembrolizumab n=11 participants at risk Subjects in this trial will receive entinostat and pembrolizumab.
Blood and lymphatic system disorders Anemia	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Gastrointestinal disorders Nausea	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Gastrointestinal disorders General disorders and administration site conditions - Other, specify	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
General disorders fatigue	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Hepatobiliary disorders Hepatic pain	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Infections and infestations Urinary tract infection	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Metabolism and nutrition disorders Dehydration	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Musculoskeletal and connective tissue disorders Back pain	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Musculoskeletal and connective tissue disorders Tumor pain	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Nervous system disorders Encephalopathy	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Nervous system disorders Seizure	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Psychiatric disorders Hallucinations	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Renal and urinary disorders Acute kidney injury	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Vascular disorders Hematoma	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.

Other adverse events

Measure	Single Arm: Entinostat + Pembrolizumab n=11 participants at risk Subjects in this trial will receive entinostat and pembrolizumab.
Nervous system disorders Radiculitis	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Psychiatric disorders Anxiety	36.4% 4/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Blood and lymphatic system disorders Anemia	72.7% 8/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Blood and lymphatic system disorders Eosinophilia	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Cardiac disorders Atrial fibrillation	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Cardiac disorders Palpitation	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Cardiac disorders Sinus bradycardia	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Ear and labyrinth disorders Hearing impaired	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Endocrine disorders Adrenal insufficiency	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Endocrine disorders Hyperthyroidism	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Endocrine disorders Hypothyroidism	27.3% 3/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Eye disorders Blurred vision	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Eye disorders Dry eye	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Eye disorders Eye disorders - Other, specify	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Gastrointestinal disorders Abdominal pain	27.3% 3/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Gastrointestinal disorders Constipation	36.4% 4/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Gastrointestinal disorders Diarrhea	63.6% 7/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Gastrointestinal disorders Dry mouth	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Gastrointestinal disorders Dyspepsia	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Gastrointestinal disorders Gastroesophageal reflux disease	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Gastrointestinal disorders Nausea	54.5% 6/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Gastrointestinal disorders Vomiting	27.3% 3/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
General disorders Chills	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Gastrointestinal disorders Edema limbs	36.4% 4/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
General disorders Fatigue	100.0% 11/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
General disorders Fever	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
General disorders Malaise	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
General disorders Pain	27.3% 3/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Hepatobiliary disorders Hepatic pain	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Infections and infestations Infections and infestations - Other, specify	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Infections and infestations Sinusitis	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Injury, poisoning and procedural complications Bruising	27.3% 3/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Investigations Alanine aminotransferase increased	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Investigations Alkaline phosphatase increased	81.8% 9/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Investigations Aspartate aminotransferase increased	45.5% 5/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Investigations Blood lactate dehydrogenase increased	45.5% 5/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Investigations Creatinine increased	54.5% 6/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Investigations Investigations - Other, specify	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Investigations Lipase increased	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Investigations Lymphocyte count decreased	100.0% 11/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Investigations Neutrophil count decreased	45.5% 5/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Investigations Platelet count decreased	54.5% 6/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Investigations Serum amylase increased	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Investigations Thyroid stimulating hormone increased	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Investigations Weight loss	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Investigations White blood cell decreased	45.5% 5/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Metabolism and nutrition disorders Anorexia	27.3% 3/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Metabolism and nutrition disorders Dehydration	45.5% 5/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Metabolism and nutrition disorders Hyperglycemia	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Metabolism and nutrition disorders Hyperkalemia	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Metabolism and nutrition disorders Hyperlipidemia	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Metabolism and nutrition disorders Hypermagnesemia	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Metabolism and nutrition disorders Hypoalbuminemia	90.9% 10/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Metabolism and nutrition disorders Hypocalcemia	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Metabolism and nutrition disorders Hypokalemia	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Metabolism and nutrition disorders Hypomagnesemia	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Metabolism and nutrition disorders Hyponatremia	63.6% 7/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Metabolism and nutrition disorders Hypophosphatemia	63.6% 7/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Metabolism and nutrition disorders Obesity	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Musculoskeletal and connective tissue disorders Arthralgia	81.8% 9/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Musculoskeletal and connective tissue disorders Arthritis	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Musculoskeletal and connective tissue disorders Back pain	27.3% 3/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Musculoskeletal and connective tissue disorders Flank pain	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	27.3% 3/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Musculoskeletal and connective tissue disorders Myalgia	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Musculoskeletal and connective tissue disorders Neck pain	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Musculoskeletal and connective tissue disorders Osteoporosis	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Musculoskeletal and connective tissue disorders Pain in extremity	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor hemorrhage	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	54.5% 6/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Nervous system disorders Dizziness	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Nervous system disorders Dysgeusia	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Nervous system disorders Headache	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Nervous system disorders Memory impairment	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Nervous system disorders Nervous system disorders - Other, specify	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Nervous system disorders Paresthesia	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Nervous system disorders Peripheral sensory neuropathy	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Psychiatric disorders Depression	36.4% 4/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Psychiatric disorders Insomnia	45.5% 5/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Psychiatric disorders Psychiatric disorders - Other, specify	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Renal and urinary disorders Acute kidney injury	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Renal and urinary disorders Chronic kidney disease	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Renal and urinary disorders Dysuria	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Renal and urinary disorders Renal and urinary disorders - Other, specify	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Renal and urinary disorders Urinary retention	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Respiratory, thoracic and mediastinal disorders Cough	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Respiratory, thoracic and mediastinal disorders Dyspnea	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Respiratory, thoracic and mediastinal disorders Hypoxia	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Respiratory, thoracic and mediastinal disorders Nasal congestion	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Respiratory, thoracic and mediastinal disorders Rhinorrhea	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Respiratory, thoracic and mediastinal disorders Sore throat	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Skin and subcutaneous tissue disorders Alopecia	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Skin and subcutaneous tissue disorders Dry skin	27.3% 3/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Skin and subcutaneous tissue disorders Pruritus	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	63.6% 7/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Skin and subcutaneous tissue disorders Skin hypopigmentation	27.3% 3/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Vascular disorders Hematoma	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Vascular disorders Hypertension	54.5% 6/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Vascular disorders Hypotension	18.2% 2/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.
Vascular disorders Thromboembolic event	9.1% 1/11 • Up to 90 days. Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was considered as a serious adverse event.

Additional Information

Melahat G. Canter MD MS, Clinical Trial Analyst

University of North Carolina Lineberger Comprehensive Cancer Center

Phone: (919) 962-0000

Email: Melahat_Canter@med.unc.edu

Results disclosure agreements

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