Trial Outcomes & Findings for Phase 2 Study of Carfilzomib in Relapsed and Refractory Multiple Myeloma (NCT NCT00511238)

NCT ID: NCT00511238

Last Updated: 2017-08-31

Results Overview

For both A0 and A1, to evaluate the best overall response rate (stringent complete response \[sCR\]+ complete response \[CR\]+ very good partial response \[VGPR\]+ partial response \[PR\]) in patients with multiple myeloma who had previously received bortezomib and either thalidomide or lenalidomide, had relapsed after two or more therapies, and were refractory to the most recently received therapy

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 312 participants
• Primary outcome timeframe: A0: Subjects evaluated for disease response on Day 24 of Cycles 2, 4, 6, 9, and 12. Onset of response measured on Day 15 of Cycle 1. A1: Subjects evaluated for disease response on Day 15 of Cycle 1, Day 1 of Cycles 2 through 12 and at End of Study.
• Results posted on: 2017-08-31

Participant Flow

Results of this study are reported in 2 parts, depending on whether a patient was enrolled and treated under the original protocol (referred to as 'A0') or under Amendment 1 and subsequent amendments (referred to as 'A1').

Participant milestones

Measure	Carfilzomib (A0) Subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles	Carfilzomib (A1) In Cycle 1, subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16. If all doses are administered and well-tolerated over the 28-day cycle, beginning with Cycle 2 the dose will escalate to 27 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles.
Overall Study STARTED	46	266
Overall Study COMPLETED	4	40
Overall Study NOT COMPLETED	42	226

Reasons for withdrawal

Measure	Carfilzomib (A0) Subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles	Carfilzomib (A1) In Cycle 1, subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16. If all doses are administered and well-tolerated over the 28-day cycle, beginning with Cycle 2 the dose will escalate to 27 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles.
Overall Study Adverse Event	13	33
Overall Study Withdrawal by Subject	2	22
Overall Study Progressive Disease	23	157
Overall Study various reasons	4	14

Baseline Characteristics

Phase 2 Study of Carfilzomib in Relapsed and Refractory Multiple Myeloma

Baseline characteristics by cohort

Measure	Carfilzomib (A0) n=46 Participants Subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 of 28 day cycle	Carfilzomib (A1) n=266 Participants In Cycle 1, subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16. If all doses are administered and well-tolerated over the 28-day cycle, beginning with Cycle 2 the dose will escalate to 27 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles.	Total n=312 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	26 Participants n=5 Participants	146 Participants n=7 Participants	172 Participants n=5 Participants
Age, Categorical >=65 years	20 Participants n=5 Participants	120 Participants n=7 Participants	140 Participants n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants	111 Participants n=7 Participants	132 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	155 Participants n=7 Participants	180 Participants n=5 Participants

PRIMARY outcome

Timeframe: A0: Subjects evaluated for disease response on Day 24 of Cycles 2, 4, 6, 9, and 12. Onset of response measured on Day 15 of Cycle 1. A1: Subjects evaluated for disease response on Day 15 of Cycle 1, Day 1 of Cycles 2 through 12 and at End of Study.

Population: Analysis population described in reporting groups below

For both A0 and A1, to evaluate the best overall response rate (stringent complete response [sCR]+ complete response [CR]+ very good partial response [VGPR]+ partial response [PR]) in patients with multiple myeloma who had previously received bortezomib and either thalidomide or lenalidomide, had relapsed after two or more therapies, and were refractory to the most recently received therapy

Outcome measures

Measure	Carfilzomib (A0) n=42 Participants Subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 of a 28 day cycle Response-evaluable Population: Enrolled patients who completed at least 1 cycle of carfilzomib and who underwent disease assessments at Screening, Cycle 1 Day 15, and Cycle 2 Day 24. This analysis set also included patients who discontinued treatment during this time due to an AE that was considered probably related to carfilzomib.	Carfilzomib (A1) n=257 Participants In Cycle 1, subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16.If all doses are administered and well-tolerated over the 28-day cycle, beginning with Cycle 2 the dose will escalate to 27 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles. Response-Evaluable Population: 1. had measurable disease at Baseline 2. received at least 1 dose of carfilzomib 3. underwent baseline disease response assessments and at least 1 post-baseline disease assessment, or discontinued protocol treatment before Cycle 2 Day 1 due to an AE that was considered to be possibly or probably related to carfilzomib
Best Overall Response Rate (ORR)	16.7 % of participants w/ PR or better Interval 6.97 to 31.36	23.7 % of participants w/ PR or better Interval 18.67 to 29.42

SECONDARY outcome

Timeframe: Response assessments same as described in primary outcome measure

Population: Response-evaluable Population: Enrolled patients who completed at least 1 cycle of carfilzomib and who underwent disease assessments at Screening, Cycle 1 Day 15, and Cycle 2 Day 24. This analysis set also included patients who discontinued treatment during this time due to an AE that was considered probably related to carfilzomib.

sCR, CR, VGPR, PR, and minimal response (MR)

Outcome measures

Measure	Carfilzomib (A0) n=42 Participants Subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 of a 28 day cycle Response-evaluable Population: Enrolled patients who completed at least 1 cycle of carfilzomib and who underwent disease assessments at Screening, Cycle 1 Day 15, and Cycle 2 Day 24. This analysis set also included patients who discontinued treatment during this time due to an AE that was considered probably related to carfilzomib.	Carfilzomib (A1) In Cycle 1, subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16.If all doses are administered and well-tolerated over the 28-day cycle, beginning with Cycle 2 the dose will escalate to 27 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles. Response-Evaluable Population: 1. had measurable disease at Baseline 2. received at least 1 dose of carfilzomib 3. underwent baseline disease response assessments and at least 1 post-baseline disease assessment, or discontinued protocol treatment before Cycle 2 Day 1 due to an AE that was considered to be possibly or probably related to carfilzomib
Clinical Benefit Response (CBR) (A0 Only) Clinical Benefit Response (sCR+CR+VGPR+PR+MR)	10 participants	—
Clinical Benefit Response (CBR) (A0 Only) Complete Response	0 participants	—
Clinical Benefit Response (CBR) (A0 Only) Very Good Partial Response	0 participants	—
Clinical Benefit Response (CBR) (A0 Only) Partial Response	7 participants	—
Clinical Benefit Response (CBR) (A0 Only) Minimal Response	3 participants	—

SECONDARY outcome

Timeframe: Response assessments same as described in primary outcome measure

Population: Response-Evaluable Population: 1. had measurable disease at Baseline 2. received at least 1 dose of carfilzomib 3. underwent baseline disease response assessments and at least 1 post-baseline disease assessment, or discontinued protocol treatment before Cycle 2 Day 1 due to an AE that was considered to be possibly or probably related to carfilzomib

sCR, CR, VGPR, PR, and minimal response (MR)

Outcome measures

Measure	Carfilzomib (A0) n=257 Participants Subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 of a 28 day cycle Response-evaluable Population: Enrolled patients who completed at least 1 cycle of carfilzomib and who underwent disease assessments at Screening, Cycle 1 Day 15, and Cycle 2 Day 24. This analysis set also included patients who discontinued treatment during this time due to an AE that was considered probably related to carfilzomib.	Carfilzomib (A1) In Cycle 1, subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16.If all doses are administered and well-tolerated over the 28-day cycle, beginning with Cycle 2 the dose will escalate to 27 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles. Response-Evaluable Population: 1. had measurable disease at Baseline 2. received at least 1 dose of carfilzomib 3. underwent baseline disease response assessments and at least 1 post-baseline disease assessment, or discontinued protocol treatment before Cycle 2 Day 1 due to an AE that was considered to be possibly or probably related to carfilzomib
Clinical Benefit Response (CBR) (A1 Only) Clinical Benefit Response (sCR+CR+VGPR+PR+MR)	95 participants	—
Clinical Benefit Response (CBR) (A1 Only) Complete Response	1 participants	—
Clinical Benefit Response (CBR) (A1 Only) Very Good Partial Response	13 participants	—
Clinical Benefit Response (CBR) (A1 Only) Partial Response	47 participants	—
Clinical Benefit Response (CBR) (A1 Only) Minimal Response	34 participants	—

SECONDARY outcome

Timeframe: Response assessments same as described in primary outcome measure

Population: Subjects with overall response within the response-evaluable population were included in the analysis of DOR. See analysis population description of response-evaluable population above.

Duration of response (DOR) was calculated separately for subjects with clinical benefit response or overall response. DOR is defined as the time from first evidence of PR or better (for overall response) and MR or better (for clinical benefit response) to start of disease progression or death.

Outcome measures

Measure	Carfilzomib (A0) n=7 Participants Subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 of a 28 day cycle Response-evaluable Population: Enrolled patients who completed at least 1 cycle of carfilzomib and who underwent disease assessments at Screening, Cycle 1 Day 15, and Cycle 2 Day 24. This analysis set also included patients who discontinued treatment during this time due to an AE that was considered probably related to carfilzomib.	Carfilzomib (A1) In Cycle 1, subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16.If all doses are administered and well-tolerated over the 28-day cycle, beginning with Cycle 2 the dose will escalate to 27 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles. Response-Evaluable Population: 1. had measurable disease at Baseline 2. received at least 1 dose of carfilzomib 3. underwent baseline disease response assessments and at least 1 post-baseline disease assessment, or discontinued protocol treatment before Cycle 2 Day 1 due to an AE that was considered to be possibly or probably related to carfilzomib
Duration of Response (A0 Only)	219 days Interval 57.0 to The upper limit of the 95% confidence interval was not calculable/available (not estimable \[NE\]) because an insufficient number of participants reached the event at the final time point for assessment (3 of 7 responders had an event).	—

SECONDARY outcome

Timeframe: Response assessments same as described in primary outcome measure

Population: Subjects with overall response within the response-evaluable population were included in the analysis of DOR. See overall analysis population description of response-evaluable population above.

Duration of response (DOR) was calculated separately for subjects with clinical benefit response or overall response. DOR is defined as the time from first evidence of PR or better (for overall response) and MR or better (for clinical benefit response) to start of disease progression or death.

Outcome measures

Measure	Carfilzomib (A0) n=61 Participants Subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 of a 28 day cycle Response-evaluable Population: Enrolled patients who completed at least 1 cycle of carfilzomib and who underwent disease assessments at Screening, Cycle 1 Day 15, and Cycle 2 Day 24. This analysis set also included patients who discontinued treatment during this time due to an AE that was considered probably related to carfilzomib.	Carfilzomib (A1) n=95 Participants In Cycle 1, subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16.If all doses are administered and well-tolerated over the 28-day cycle, beginning with Cycle 2 the dose will escalate to 27 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles. Response-Evaluable Population: 1. had measurable disease at Baseline 2. received at least 1 dose of carfilzomib 3. underwent baseline disease response assessments and at least 1 post-baseline disease assessment, or discontinued protocol treatment before Cycle 2 Day 1 due to an AE that was considered to be possibly or probably related to carfilzomib
Duration of Response (A1 Only)	7.8 months Interval 5.6 to 9.2	8.3 months Interval 6.5 to 9.7

SECONDARY outcome

Timeframe: Response assessments same as described in primary outcome measure

Population: Response-evaluable Population: Enrolled patients who completed at least 1 cycle of carfilzomib and who underwent disease assessments at Screening, Cycle 1 Day 15, and Cycle 2 Day 24. This analysis set also included patients who discontinued treatment during this time due to an AE that was considered probably related to carfilzomib.

Time to progression (TTP) is defined as the time from the study entry (first dose of carfilzomib) to disease progression.

Outcome measures

Measure	Carfilzomib (A0) n=42 Participants Subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 of a 28 day cycle Response-evaluable Population: Enrolled patients who completed at least 1 cycle of carfilzomib and who underwent disease assessments at Screening, Cycle 1 Day 15, and Cycle 2 Day 24. This analysis set also included patients who discontinued treatment during this time due to an AE that was considered probably related to carfilzomib.	Carfilzomib (A1) In Cycle 1, subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16.If all doses are administered and well-tolerated over the 28-day cycle, beginning with Cycle 2 the dose will escalate to 27 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles. Response-Evaluable Population: 1. had measurable disease at Baseline 2. received at least 1 dose of carfilzomib 3. underwent baseline disease response assessments and at least 1 post-baseline disease assessment, or discontinued protocol treatment before Cycle 2 Day 1 due to an AE that was considered to be possibly or probably related to carfilzomib
Time to Progression (A0 Only)	3.5 months Interval 2.4 to 6.7	—

SECONDARY outcome

Timeframe: Response assessments same as described in primary outcome measure

Population: Response-Evaluable Population: 1. had measurable disease at Baseline 2. received at least 1 dose of carfilzomib 3. underwent baseline disease response assessments and at least 1 post-baseline disease assessment, or discontinued protocol treatment before Cycle 2 Day 1 due to an AE that was considered to be possibly or probably related to carfilzomib

Time to progression (TTP) is defined as the time from the study entry (first dose of carfilzomib) to disease progression.

Outcome measures

Measure	Carfilzomib (A0) n=257 Participants Subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 of a 28 day cycle Response-evaluable Population: Enrolled patients who completed at least 1 cycle of carfilzomib and who underwent disease assessments at Screening, Cycle 1 Day 15, and Cycle 2 Day 24. This analysis set also included patients who discontinued treatment during this time due to an AE that was considered probably related to carfilzomib.	Carfilzomib (A1) In Cycle 1, subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16.If all doses are administered and well-tolerated over the 28-day cycle, beginning with Cycle 2 the dose will escalate to 27 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles. Response-Evaluable Population: 1. had measurable disease at Baseline 2. received at least 1 dose of carfilzomib 3. underwent baseline disease response assessments and at least 1 post-baseline disease assessment, or discontinued protocol treatment before Cycle 2 Day 1 due to an AE that was considered to be possibly or probably related to carfilzomib
Time to Progression (A1 Only)	3.9 months Interval 2.8 to 4.8	—

SECONDARY outcome

Timeframe: Response assessments same as described in primary outcome measure

Population: Response-evaluable Population: Enrolled patients who completed at least 1 cycle of carfilzomib and who underwent disease assessments at Screening, Cycle 1 Day 15, and Cycle 2 Day 24. This analysis set also included patients who discontinued treatment during this time due to an AE that was considered probably related to carfilzomib.

The PFS was defined as the time from the start of treatment to progressive disease (PD) determined by PI or until death.

Outcome measures

Measure	Carfilzomib (A0) n=42 Participants Subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 of a 28 day cycle Response-evaluable Population: Enrolled patients who completed at least 1 cycle of carfilzomib and who underwent disease assessments at Screening, Cycle 1 Day 15, and Cycle 2 Day 24. This analysis set also included patients who discontinued treatment during this time due to an AE that was considered probably related to carfilzomib.	Carfilzomib (A1) In Cycle 1, subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16.If all doses are administered and well-tolerated over the 28-day cycle, beginning with Cycle 2 the dose will escalate to 27 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles. Response-Evaluable Population: 1. had measurable disease at Baseline 2. received at least 1 dose of carfilzomib 3. underwent baseline disease response assessments and at least 1 post-baseline disease assessment, or discontinued protocol treatment before Cycle 2 Day 1 due to an AE that was considered to be possibly or probably related to carfilzomib
Progression-free Survival (A0 Only)	3.5 months Interval 2.4 to 6.7	—

SECONDARY outcome

Timeframe: Response assessments same as described in primary outcome measure

Population: Response-Evaluable Population: 1. had measurable disease at Baseline 2. received at least 1 dose of carfilzomib 3. underwent baseline disease response assessments and at least 1 post-baseline disease assessment, or discontinued protocol treatment before Cycle 2 Day 1 due to an AE that was considered to be possibly or probably related to carfilzomib

The PFS was defined as the time from the start of treatment to progressive disease (PD) determined by PI or until death.

Outcome measures

Measure	Carfilzomib (A0) n=257 Participants Subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 of a 28 day cycle Response-evaluable Population: Enrolled patients who completed at least 1 cycle of carfilzomib and who underwent disease assessments at Screening, Cycle 1 Day 15, and Cycle 2 Day 24. This analysis set also included patients who discontinued treatment during this time due to an AE that was considered probably related to carfilzomib.	Carfilzomib (A1) In Cycle 1, subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16.If all doses are administered and well-tolerated over the 28-day cycle, beginning with Cycle 2 the dose will escalate to 27 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles. Response-Evaluable Population: 1. had measurable disease at Baseline 2. received at least 1 dose of carfilzomib 3. underwent baseline disease response assessments and at least 1 post-baseline disease assessment, or discontinued protocol treatment before Cycle 2 Day 1 due to an AE that was considered to be possibly or probably related to carfilzomib
Progression-free Survival (A1 Only)	3.7 months Interval 2.8 to 4.6	—

SECONDARY outcome

Timeframe: Patients were to be followed by telephone contact for disease progression and OS every 3 months after study discontinuation for the first year and every 6 months thereafter for up to 2 years

The time from start of treatment to death due to any cause OS was to be censored on the date the subject was last known to be alive for those who were alive or lost to follow-up as of a data analysis cutoff date.

Outcome measures

Measure	Carfilzomib (A0) n=266 Participants Subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 of a 28 day cycle Response-evaluable Population: Enrolled patients who completed at least 1 cycle of carfilzomib and who underwent disease assessments at Screening, Cycle 1 Day 15, and Cycle 2 Day 24. This analysis set also included patients who discontinued treatment during this time due to an AE that was considered probably related to carfilzomib.	Carfilzomib (A1) n=257 Participants In Cycle 1, subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16.If all doses are administered and well-tolerated over the 28-day cycle, beginning with Cycle 2 the dose will escalate to 27 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles. Response-Evaluable Population: 1. had measurable disease at Baseline 2. received at least 1 dose of carfilzomib 3. underwent baseline disease response assessments and at least 1 post-baseline disease assessment, or discontinued protocol treatment before Cycle 2 Day 1 due to an AE that was considered to be possibly or probably related to carfilzomib
Overall Survival (A1 Only)	15.4 months Interval 12.5 to 19.0	15.6 months Interval 13.0 to 19.2

Adverse Events

Carfilzomib (A0)

Serious events: 20 serious events

Other events: 46 other events

Deaths: 0 deaths

Carfilzomib (A1)

Serious events: 126 serious events

Other events: 266 other events

Deaths: 0 deaths

Serious adverse events

Measure	Carfilzomib (A0) n=46 participants at risk Subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 of a 28 day cycle	Carfilzomib (A1) n=266 participants at risk In Cycle 1, subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16.If all doses are administered and well-tolerated over the 28-day cycle, beginning with Cycle 2 the dose will escalate to 27 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles.
Psychiatric disorders Confusional state	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Psychiatric disorders Delirium	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Renal and urinary disorders Haematuria	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Renal and urinary disorders Renal impairment	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	1.1% 3/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Cardiac disorders Cardiac failure congestive	4.3% 2/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	3.0% 8/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Cardiac disorders Cardiac failure	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.00% 0/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Cardiac disorders Cardiomyopathy	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.00% 0/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Cardiac disorders Myocardial ischaemia	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.75% 2/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Cardiac disorders Supraventricular tachycardia	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.00% 0/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
General disorders Disease progression	10.9% 5/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	6.0% 16/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
General disorders Multi-organ failure	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.00% 0/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
General disorders Non-cardiac chest pain	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	1.1% 3/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
General disorders Pyrexia	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	3.0% 8/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Pneumonia	10.9% 5/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	8.6% 23/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Bacteraemia	4.3% 2/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Clostridium colitis	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.00% 0/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Klebsiella sepsis	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.00% 0/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Lobar pneumonia	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.75% 2/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Sepsis	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	1.5% 4/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Injury, poisoning and procedural complications Post procedural haemorrhage	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.00% 0/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hypercalcaemia	4.3% 2/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	2.3% 6/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hyponatraemia	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Musculoskeletal and connective tissue disorders Bone pain	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.75% 2/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Musculoskeletal and connective tissue disorders Pathological fracture	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	3.0% 8/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour lysis syndrome	4.3% 2/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.00% 0/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasmacytoma	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.75% 2/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Renal and urinary disorders Renal failure acute	8.7% 4/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	3.4% 9/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Renal and urinary disorders Nephrolithiasis	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.00% 0/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Renal and urinary disorders Renal failure	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	1.1% 3/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	1.9% 5/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.75% 2/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Blood and lymphatic system disorders Anaemia	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	1.9% 5/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	1.9% 5/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.75% 2/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Cardiac disorders Cardiac arrest	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	1.5% 4/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Cardiac disorders Atrial fibrillation	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.75% 2/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Cardiac disorders Acute coronary syndrome	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Cardiac disorders Acute myocardial infarction	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Cardiac disorders Aortic valve stenosis	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Cardiac disorders Arrhythmia	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Cardiac disorders Atrial flutter	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Cardiac disorders Congestive cardiomyopathy	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Cardiac disorders Ventricular dysfunction	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Endocrine disorders Hypercalcaemia of malignancy	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Eye disorders Diplopia	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Gastrointestinal disorders Diarrhoea	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Gastrointestinal disorders Dysphagia	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Gastrointestinal disorders Intra-abdominal haemorrhage	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Gastrointestinal disorders Pancreatitis	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Gastrointestinal disorders Vomiting	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
General disorders Asthenia	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
General disorders Chills	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
General disorders Death	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
General disorders Infusion related reaction	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
General disorders Pain	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Hepatobiliary disorders Hepatic failure	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.75% 2/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Immune system disorders Hypersensitivity	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Cellulitis	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.75% 2/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Upper respiratory tract infection	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.75% 2/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Central line infection	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Chronic sinusitis	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Ear infection	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Escherichia bacteraemia	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Fusobacterium infection	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Gastroenteritis viral	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Infection	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Otitis media	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Parainfluenzae virus infection	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Pneumonia respiratory syncytial viral	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Respiratory syncytial virus infection	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Septic shock	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Blood creatinine increased	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	1.9% 5/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Alanine aminotransferase increased	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Aspartate aminotransferase increased	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Hepatic enzyme abnormal	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Transaminases increased	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Metabolism and nutrition disorders Dehydration	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	1.1% 3/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Metabolism and nutrition disorders Fluid overload	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.75% 2/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Musculoskeletal and connective tissue disorders Shoulder pain	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Nervous system disorders Spinal cord compression	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	2.3% 6/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Nervous system disorders Syncope	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.75% 2/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Nervous system disorders Haemorrhage intracranial	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Nervous system disorders Hepatic encephalopathy	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Nervous system disorders Migraine	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Nervous system disorders Neuropathy	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Nervous system disorders Syncope vasovagal	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Nervous system disorders Transient ischaemic attack	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Psychiatric disorders Mental status changes	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.75% 2/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.75% 2/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.75% 2/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Pulmonary alveolar haemorrhage	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Vascular disorders Hypotension	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	1.5% 4/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Vascular disorders Deep vein thrombosis	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.75% 2/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Vascular disorders Hypertension	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.

Other adverse events

Measure	Carfilzomib (A0) n=46 participants at risk Subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 of a 28 day cycle	Carfilzomib (A1) n=266 participants at risk In Cycle 1, subjects will receive carfilzomib 20 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16.If all doses are administered and well-tolerated over the 28-day cycle, beginning with Cycle 2 the dose will escalate to 27 mg/m2 intravenously on Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles.
Blood and lymphatic system disorders Anaemia	73.9% 34/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	45.9% 122/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Blood and lymphatic system disorders Thrombocytopenia	50.0% 23/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	38.7% 103/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Blood and lymphatic system disorders Lymphopenia	34.8% 16/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	23.3% 62/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Blood and lymphatic system disorders Leukopenia	21.7% 10/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	13.9% 37/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Blood and lymphatic system disorders Neutropenia	21.7% 10/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	18.0% 48/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Gastrointestinal disorders Nausea	34.8% 16/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	44.7% 119/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Gastrointestinal disorders Diarrhoea	32.6% 15/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	32.3% 86/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Gastrointestinal disorders Vomiting	17.4% 8/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	22.2% 59/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Gastrointestinal disorders Constipation	13.0% 6/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	21.1% 56/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Gastrointestinal disorders Abdominal pain	10.9% 5/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	6.0% 16/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Gastrointestinal disorders Dyspepsia	10.9% 5/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	9.8% 26/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
General disorders Fatigue	69.6% 32/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	48.9% 130/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
General disorders Pyrexia	32.6% 15/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	31.2% 83/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
General disorders Asthenia	15.2% 7/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	15.0% 40/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
General disorders Oedema peripheral	19.6% 9/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	23.3% 62/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
General disorders Chest discomfort	10.9% 5/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	2.3% 6/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
General disorders Chills	10.9% 5/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	15.8% 42/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
General disorders Disease progression	10.9% 5/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	6.4% 17/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
General disorders Injection site irritation	8.7% 4/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	1.5% 4/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Hepatobiliary disorders Hyperbilirubinaemia	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	1.1% 3/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Upper respiratory tract infection	37.0% 17/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	26.7% 71/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Pneumonia	10.9% 5/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	12.0% 32/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Nasopharyngitis	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	4.9% 13/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Blood creatinine increased	34.8% 16/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	25.2% 67/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Blood bicarbonate decreased	30.4% 14/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	2.3% 6/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Aspartate aminotransfersae increased	19.6% 9/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	10.2% 27/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Blood chloride increased	17.4% 8/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Blood urea increased	15.2% 7/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	1.5% 4/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Blood uric acid increased	15.2% 7/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	5.6% 15/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Blood glucose increased	10.9% 5/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.75% 2/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Blood lactate dehydrogenase increased	8.7% 4/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	3.0% 8/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Carbon dioxide decreased	8.7% 4/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.75% 2/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Alanine aminotransferase decreased	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Alanine aminotransferase increased	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	7.5% 20/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Psychiatric disorders Insomnia	26.1% 12/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	14.7% 39/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Psychiatric disorders Confusional state	13.0% 6/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	6.4% 17/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Renal and urinary disorders Renal failure acute	8.7% 4/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	4.9% 13/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Renal and urinary disorders Proteinuria	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.00% 0/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Renal and urinary disorders Renal failure	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	3.8% 10/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Neutrophil percentage increased	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.00% 0/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations White blood cell count decreased	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	1.9% 5/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hypocalcaemia	34.8% 16/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	5.3% 14/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hypoalbuminaemia	26.1% 12/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	5.3% 14/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Metabolism and nutrition disorders Anorexia	21.7% 10/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	13.2% 35/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Cough	28.3% 13/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	24.4% 65/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Dyspnoea	28.3% 13/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	33.8% 90/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Crackles lung	8.7% 4/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	3.4% 9/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hypercalcaemia	15.2% 7/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	13.5% 36/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hypokalaemia	15.2% 7/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	10.9% 29/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hyperphosphataemia	13.0% 6/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	2.6% 7/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hypophosphataemia	13.0% 6/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	12.0% 32/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hypermagnesaemia	10.9% 5/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	1.1% 3/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Metabolism and nutrition disorders Decreased appetite	8.7% 4/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	7.1% 19/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hypoglycaemia	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	2.3% 6/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Musculoskeletal and connective tissue disorders Chest wall pain	17.4% 8/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	12.0% 32/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Musculoskeletal and connective tissue disorders Muscle spasms	17.4% 8/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	12.0% 32/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Musculoskeletal and connective tissue disorders Pain in extremity	17.4% 8/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	11.7% 31/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Musculoskeletal and connective tissue disorders Arthralgia	13.0% 6/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	18.4% 49/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Musculoskeletal and connective tissue disorders Back pain	13.0% 6/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	23.7% 63/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Musculoskeletal and connective tissue disorders Bone pain	10.9% 5/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	8.6% 23/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Musculoskeletal and connective tissue disorders Shoulder pain	10.9% 5/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	10.5% 28/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Musculoskeletal and connective tissue disorders Pain in jaw	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Nervous system disorders Headache	26.1% 12/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	27.8% 74/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Nervous system disorders Hypoaesthesia	10.9% 5/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	9.4% 25/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Nervous system disorders Areflexia	8.7% 4/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	5.3% 14/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Nervous system disorders Neuropathic pain	8.7% 4/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	3.4% 9/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Nervous system disorders Neuropathy peripheral	8.7% 4/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	6.4% 17/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Nervous system disorders Dizziness	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	11.3% 30/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Nervous system disorders Hyporeflexia	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	6.8% 18/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Nervous system disorders Neuropathy	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	3.4% 9/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Nervous system disorders Paraesthesia	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	7.5% 20/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
General disorders Infusion site pain	4.3% 2/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	9.0% 24/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
General disorders Pain	4.3% 2/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	9.0% 24/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Infections and infestations Urinary tract infection	0.00% 0/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	7.1% 19/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Injury, poisoning and procedural complications Contusion	4.3% 2/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	5.3% 14/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Weight decreased	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	7.5% 20/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hyponatraemia	21.7% 10/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	11.7% 31/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hyperglycaemia	26.1% 12/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	9.8% 26/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Metabolism and nutrition disorders Dehydration	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	6.8% 18/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hyperkalaemia	19.6% 9/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	5.3% 14/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Musculoskeletal and connective tissue disorders Myalgia	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	8.3% 22/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Musculoskeletal and connective tissue disorders Pathological fracture	4.3% 2/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	6.4% 17/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Psychiatric disorders Anxiety	4.3% 2/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	6.0% 16/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Psychiatric disorders Depression	4.3% 2/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	5.3% 14/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	12.4% 33/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Epistaxis	8.7% 4/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	10.9% 29/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	7.9% 21/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	15.2% 7/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	7.5% 20/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Nasal congestion	4.3% 2/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	6.4% 17/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Productive cough	8.7% 4/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	6.0% 16/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	5.3% 14/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Skin and subcutaneous tissue disorders Rash	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	7.5% 20/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Skin and subcutaneous tissue disorders Pruritus	2.2% 1/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	6.4% 17/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Vascular disorders Hypertension	8.7% 4/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	14.7% 39/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Vascular disorders Hypotension	8.7% 4/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	7.9% 21/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Gastrointestinal disorders Dry mouth	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	1.5% 4/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Blood albumin decreased	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	1.5% 4/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Blood calcium increased	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	1.9% 5/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Blood sodium decreased	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.00% 0/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Blood phosphorus decreased	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	4.5% 12/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Investigations Lymphocyte percentage decreased	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.38% 1/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hyperuricaemia	19.6% 9/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	4.1% 11/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Metabolism and nutrition disorders Hypomagnesaemia	21.7% 10/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	10.5% 28/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Bronchospasm	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	0.00% 0/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Dysphonia	6.5% 3/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	1.1% 3/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	8.7% 4/46 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.	1.9% 5/266 • All adverse events (AEs) should be reported from the time the subject signs consent through 30 days post-last dose of study drug or initiation of a new anti-cancer therapy, whichever occurs first.

Additional Information

Onyx Medical Information

Onyx Pharmaceuticals

Phone: 1-877-ONYX-121

Email: medinfo@onyx.com

Results disclosure agreements

• Principal investigator is a sponsor employee After the study is completed and all case report forms have been sent to Sponsor, Institution shall have the right to publish or otherwise make public any data resulting from the study under this agreement after publication of a multi-center publication coordinated by Sponsor with respect to the data resulting from the study, or 12 months after the Study is completed at all participating sites if a multi-center publication is not submitted by Sponsor for publication within such 12 month period.
• Publication restrictions are in place

Restriction type: OTHER