Trial Outcomes & Findings for Pembrolizumab and Decitabine for Refractory or Relapsed Acute Myeloid Leukemia (NCT NCT02996474)

NCT ID: NCT02996474

Last Updated: 2022-12-28

Results Overview

The number of patients who could be treated with a novel combination of Pembrolizumab and Decitabine in relapsed/refractory Acute Myeloid Leukemia participants without being removed from the protocol due to treatment related toxicities.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 10 participants
• Primary outcome timeframe: 24 weeks
• Results posted on: 2022-12-28

Participant Flow

Participant milestones

Measure	Pembrolizumab and Decitabine for Treatment of Acute Myeloid Leukemia Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m\^2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory Acute Myeloid Leukemia (AML).
Overall Study STARTED	10
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Measure

Pembrolizumab and Decitabine for Treatment of Acute Myeloid Leukemia Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m\^2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory Acute Myeloid Leukemia (AML).

Overall Study Physician Decision

5

Baseline Characteristics

Pembrolizumab and Decitabine for Refractory or Relapsed Acute Myeloid Leukemia

Baseline characteristics by cohort

Measure	Pembrolizumab and Decitabine for Treatment of Acute Myeloid Leukemia n=10 Participants Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m\^2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory Acute Myeloid Leukemia (AML).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 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	3 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: All patients enrolled on study.

The number of patients who could be treated with a novel combination of Pembrolizumab and Decitabine in relapsed/refractory Acute Myeloid Leukemia participants without being removed from the protocol due to treatment related toxicities.

Outcome measures

Measure

Pembrolizumab and Decitabine for Treatment of Acute Myeloid Leukemia n=10 Participants Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m\^2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory Acute Myeloid Leukemia (AML).

Feasibility of a Novel Combination of Pembrolizumab and Decitabine in Relapsed/Refractory Acute Myeloid Leukemia Participants

10 Participants

SECONDARY outcome

Timeframe: At the end of each cycle 2 (week 6), 4 (week 12), 6 (week 18), 8 (up to week 24)

Population: Includes all participants that received treatment.

Time to first response (days) is time from start of study to first response (mCR, mCRi, CR, CRi, PR, or SD) in relapsed/refractory acute myeloid leukemia (AML) participants.

Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, < 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, < 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be < 1,000/mcl and/or platelet count < 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count > 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts < 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.

Outcome measures

Measure

Pembrolizumab and Decitabine for Treatment of Acute Myeloid Leukemia n=10 Participants Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m\^2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory Acute Myeloid Leukemia (AML).

Median Days to First Response From Start of Study to Initial Achievement of First Response (mCR, mCRi, CR, CRi, PR, or SD)

42 days Interval 37.0 to 49.0

SECONDARY outcome

Timeframe: At the end of each cycle 2 (week 6), 4 (week 12), 6 (week 18), 8 (up to week 24)

Population: Includes all participants that received treatment.

Time to Best Response is defined as time (days) from start of study to initial achievement of best response. Best response is defined by the order of mCR, mCRi, CR, CRi, PR, or SD. Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, < 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, < 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be < 1,000/mcl and/or platelet count < 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count > 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts < 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.

Outcome measures

Measure

Pembrolizumab and Decitabine for Treatment of Acute Myeloid Leukemia n=10 Participants Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m\^2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory Acute Myeloid Leukemia (AML).

Median Days to Best Response From Start of Study to Initial Achievement of Best Response (by the Order of mCR, mCRi, CR, CRi, PR, or SD)

42 days Interval 39.0 to 159.0

SECONDARY outcome

Timeframe: At the end of each cycle 2 (week 6), 4 (week 12), 6 (week 18), 8 (up to week 24)

Population: Includes all participants that received treatment.

To determine duration (days) of response as defined as time from initial achievement of response to loss of response (mCR, mCRi, CR, CRi, PR, or SD).

Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, < 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, < 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be < 1,000/mcl and/or platelet count < 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count > 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts < 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.

Outcome measures

Measure

Pembrolizumab and Decitabine for Treatment of Acute Myeloid Leukemia n=10 Participants Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m\^2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory Acute Myeloid Leukemia (AML).

Median Duration (Days) of Response From Initial Achievement of Response to Loss of Response (mCR, mCRi, CR, CRi, PR, or SD)

148 days Interval 12.0 to 337.0

SECONDARY outcome

Timeframe: At the end of each cycle 2 (week 6), 4 (week 12), 6 (week 18), 8 (up to week 24)

Population: Includes all participants that received treatment.

Duration of Best Response is time (days) from initial achievement of best response to loss of best response. Best response is defined by the order of mCR, mCRi, CR, CRi, PR, or SD. Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, < 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, < 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be < 1,000/mcl and/or platelet count < 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count > 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts < 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.

Outcome measures

Measure

Pembrolizumab and Decitabine for Treatment of Acute Myeloid Leukemia n=10 Participants Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m\^2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory Acute Myeloid Leukemia (AML).

Median Duration (Days) of Best Response From Initial Achievement of Best Response to Loss of Best Response (by the Order of mCR, mCRi, CR, CRi, PR, or SD)

148 days Interval 12.0 to 316.0

SECONDARY outcome

Timeframe: from enrollment until date of death, assessed up to 24 weeks

Number of participants overall survival is defined as death from any cause

Outcome measures

Measure

Pembrolizumab and Decitabine for Treatment of Acute Myeloid Leukemia n=10 Participants Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m\^2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory Acute Myeloid Leukemia (AML).

Overall Survival

0 Participants

Adverse Events

Pembrolizumab and Decitabine for Treatment of Acute Myeloid Leukemia

Serious events: 7 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pembrolizumab and Decitabine for Treatment of Acute Myeloid Leukemia n=10 participants at risk Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory AML.
Blood and lymphatic system disorders Febrile neutropenia	60.0% 6/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Gastrointestinal disorders Diarrhoea	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
General disorders Pain	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Infections and infestations Sepsis	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Infections and infestations Wound infection bacterial	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Blood culture positive	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Metabolism and nutrition disorders Hypokalaemia	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Metabolism and nutrition disorders Hypophosphataemia	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Musculoskeletal and connective tissue disorders Back pain	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Nervous system disorders Headache	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Respiratory, thoracic and mediastinal disorders Epistaxis	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Vascular disorders Hypotension	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.

Other adverse events

Measure	Pembrolizumab and Decitabine for Treatment of Acute Myeloid Leukemia n=10 participants at risk Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory AML.
Blood and lymphatic system disorders Increased tendency to bruise	30.0% 3/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Blood and lymphatic system disorders Petechiae	40.0% 4/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Cardiac disorders Atrial flutter	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Cardiac disorders Cardiomegaly	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Cardiac disorders Dizziness	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Cardiac disorders Dyspnoea	50.0% 5/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Cardiac disorders Localised oedema	40.0% 4/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Cardiac disorders Oedema peripheral	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Cardiac disorders Palpitations	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Cardiac disorders Pericardial effusion	30.0% 3/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Cardiac disorders Sinus bradycardia	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Cardiac disorders Sinus tachycardia	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Endocrine disorders Diabetes insipidus	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Endocrine disorders Hyperglycaemia	50.0% 5/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Endocrine disorders Hypoglycaemia	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Endocrine disorders Hypothyroidism	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Endocrine disorders Thyroid mass	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Eye disorders Conjunctival haemorrhage	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Eye disorders Conjunctivitis	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Eye disorders Dry eye	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Eye disorders Eye pain	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Eye disorders Eye symptom	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Eye disorders Myopia	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Eye disorders Nystagmus	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Eye disorders Vision blurred	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Gastrointestinal disorders Abdominal distension	30.0% 3/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Gastrointestinal disorders Abdominal pain	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Gastrointestinal disorders Anorectal discomfort	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Gastrointestinal disorders Constipation	60.0% 6/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Gastrointestinal disorders Diarrhoea	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Gastrointestinal disorders Dry mouth	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Gastrointestinal disorders Dyspepsia	30.0% 3/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Gastrointestinal disorders Dysphagia	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Gastrointestinal disorders Fecal incontinence	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Gastrointestinal disorders Gingival bleeding	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Gastrointestinal disorders Haemorrhoids	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Gastrointestinal disorders Lip ulceration	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Gastrointestinal disorders Nausea	40.0% 4/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Gastrointestinal disorders Oral hemorrhage	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Gastrointestinal disorders Oral mucosal blistering	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Gastrointestinal disorders Oral pain	40.0% 4/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Gastrointestinal disorders Perirectal abscess	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Gastrointestinal disorders Throat irritation	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Gastrointestinal disorders Vomiting	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
General disorders Chills	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
General disorders Decreased appetite	40.0% 4/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
General disorders Fatigue	80.0% 8/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
General disorders Gait disturbance	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
General disorders Generalised oedema	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
General disorders Head discomfort	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
General disorders Hematoma	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
General disorders Lethargy	40.0% 4/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
General disorders Malaise	40.0% 4/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
General disorders Non-cardiac chest pain	30.0% 3/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
General disorders Pain	40.0% 4/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
General disorders Pain in extremity	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
General disorders Vascular access complication	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
General disorders Vessel puncture site bruise	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Hepatobiliary disorders Hepatomegaly	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Hepatobiliary disorders Hypoalbuminaemia	50.0% 5/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Infections and infestations Enterococcal infection	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Infections and infestations Infections and infestations- Other, specify- Bacteremia	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Infections and infestations Paronychia	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Infections and infestations Upper respiratory tract infection	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Infections and infestations Wound infection	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Injury, poisoning and procedural complications Blister	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Injury, poisoning and procedural complications Fall	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Injury, poisoning and procedural complications Fracture	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Injury, poisoning and procedural complications Post-operative hemorrhage	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Injury, poisoning and procedural complications Skin wound	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Injury, poisoning and procedural complications Tendonitis	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Activated partial thromboplastin time prolonged	60.0% 6/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Alanine aminotransferase increased	70.0% 7/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Alkaline phosphatase increased	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Aspartate aminotransferase increased	50.0% 5/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Blood alkaline phosphatase increased	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Blood bilirubin increased	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Blood creatinine increased	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Blood thyroid stimulating hormone increased	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Blood urine present	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Body temperature increased	50.0% 5/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Electrocardiogram QT corrected interval prolonged	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Electrocardiogram QT prolonged	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Heart rate irregular	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Hypoalbuminemia	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Hyponatremia	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Imaging procedure abnormal	40.0% 4/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Influenza like illness	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Lymphocyte count decreased	30.0% 3/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Neutrophil count decreased	30.0% 3/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Platelet count decreased	90.0% 9/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Surgical and medical procedures - Other, specify- Skin biopsy	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Weight decreased	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Weight gain	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Weight increased	50.0% 5/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Investigations Weight loss	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Metabolism and nutrition disorders Anorexia nervosa	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Metabolism and nutrition disorders Hypernatraemia	30.0% 3/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Metabolism and nutrition disorders Hyperuricaemia	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Metabolism and nutrition disorders Hypocalcaemia	40.0% 4/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Metabolism and nutrition disorders Hypokalaemia	40.0% 4/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Metabolism and nutrition disorders Hypomagnesaemia	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Metabolism and nutrition disorders Hyponatraemia	30.0% 3/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Metabolism and nutrition disorders Hypophosphataemia	30.0% 3/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Musculoskeletal and connective tissue disorders Arthralgia	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Musculoskeletal and connective tissue disorders Myalgia	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Musculoskeletal and connective tissue disorders Neck pain	30.0% 3/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Musculoskeletal and connective tissue disorders Pain in extremity	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Musculoskeletal and connective tissue disorders Tenosynovitis	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bartholin's cyst	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cyst	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Nervous system disorders Altered state of consciousness	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Nervous system disorders Confusional state	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Nervous system disorders Headache	40.0% 4/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Nervous system disorders Insomnia	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Nervous system disorders Somnolence	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Nervous system disorders Urinary incontinence	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Psychiatric disorders Anxiety	30.0% 3/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Renal and urinary disorders Acute kidney injury	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Renal and urinary disorders Micturition urgency	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Renal and urinary disorders Polyuria	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Renal and urinary disorders Proteinuria	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Reproductive system and breast disorders Oedema genital	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Reproductive system and breast disorders Vulvovaginal pain	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Respiratory, thoracic and mediastinal disorders Atelectasis	30.0% 3/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Respiratory, thoracic and mediastinal disorders Bronchial wall thickening	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Respiratory, thoracic and mediastinal disorders Cough	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Respiratory, thoracic and mediastinal disorders Dyspnea	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Respiratory, thoracic and mediastinal disorders Epistaxis	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Respiratory, thoracic and mediastinal disorders Lung infiltration	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Respiratory, thoracic and mediastinal disorders Nasal congestion	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Respiratory, thoracic and mediastinal disorders Pleural effusion	30.0% 3/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Respiratory, thoracic and mediastinal disorders Productive cough	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders- Bronchiectasis	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Respiratory, thoracic and mediastinal disorders Wheezing	20.0% 2/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Skin and subcutaneous tissue disorders Acne	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Skin and subcutaneous tissue disorders Dry skin	30.0% 3/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Skin and subcutaneous tissue disorders Photosensitivity reaction	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Skin and subcutaneous tissue disorders Pruritus	30.0% 3/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Surgical and medical procedures Mucositis management	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Vascular disorders Embolism	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Vascular disorders Extremity necrosis	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Vascular disorders Hypertension	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Vascular disorders Hypotension	70.0% 7/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.
Vascular disorders Intracranial hemorrhage	10.0% 1/10 • 24 weeks The Adverse Event reporting period for this study begins when the patient takes the first dose of study drug and ends with the safety follow-up visit. If an Serious Adverse Event is present at the safety follow-up visit or within 30 days of the last dose of study drug (whichever is later), it should be followed to resolution or until the Investigator assesses the subject as stable, a new anticancer therapy is initiated, or the subject is lost to follow-up or withdraws consent.

Additional Information

Christopher Hourigan

National Heart Lung and Blood Institute

Phone: +1 301 451 0257

Email: christopher.hourigan@nih.gov

Results disclosure agreements

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