Trial Outcomes & Findings for Phase II Multicenter Study of Durvalumab and Olaparib in Platinum tReated Advanced Triple Negative Breast Cancer (DORA) (NCT NCT03167619)

Last Updated: 2022-09-13

Results Overview

PFS, defined as the time from randomization to the first occurrence of disease progression or death from any cause on study for olaparib alone. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Death on study is defined as death from any cause within 30 days of the last dose of study treatment regimen. Reported as events (disease progression or death) per month.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

45 participants

Primary outcome timeframe

From date of randomization until the date of documented progression or date of death, whichever came first, approximately 1 year.

Results posted on

2022-09-13

Participant Flow

Participant milestones

Participant milestones
Measure	A - Olaparib Alone Twice daily oral Olaparib 300mg alone as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. Olaparib Oral Product: olaparib 300mg twice daily	B - Olaparib Plus Durvalumab Twice daily oral olaparib plus intravenous Durvalumab every 4 weeks as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. Olaparib Oral Product in combination with Durvalumab: olaparib 300mg twice daily plus intravenous durvalumab every 28 days
Overall Study STARTED	23	22
Overall Study COMPLETED	11	11
Overall Study NOT COMPLETED	12	11

Reasons for withdrawal

Reasons for withdrawal
Measure	A - Olaparib Alone Twice daily oral Olaparib 300mg alone as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. Olaparib Oral Product: olaparib 300mg twice daily	B - Olaparib Plus Durvalumab Twice daily oral olaparib plus intravenous Durvalumab every 4 weeks as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. Olaparib Oral Product in combination with Durvalumab: olaparib 300mg twice daily plus intravenous durvalumab every 28 days
Overall Study Death	11	8
Overall Study Withdrawal by Subject	1	2
Overall Study Physician Decision	0	1

Baseline Characteristics

Phase II Multicenter Study of Durvalumab and Olaparib in Platinum tReated Advanced Triple Negative Breast Cancer (DORA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	A - Olaparib Alone n=23 Participants Twice daily oral Olaparib 300mg alone as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. Olaparib Oral Product: olaparib 300mg twice daily	B - Olaparib Plus Durvalumab n=22 Participants Twice daily oral olaparib plus intravenous Durvalumab every 4 weeks as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. Olaparib Oral Product in combination with Durvalumab: olaparib 300mg twice daily plus intravenous durvalumab every 28 days	Total n=45 Participants Total of all reporting groups
Age, Continuous	52.4 years STANDARD_DEVIATION 11.9 • n=93 Participants	49.5 years STANDARD_DEVIATION 11.7 • n=4 Participants	51 years STANDARD_DEVIATION 11.8 • n=27 Participants
Sex: Female, Male Female	23 Participants n=93 Participants	22 Participants n=4 Participants	45 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	22 Participants n=93 Participants	22 Participants n=4 Participants	44 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	16 Participants n=93 Participants	18 Participants n=4 Participants	34 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) White	5 Participants n=93 Participants	4 Participants n=4 Participants	9 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants

PRIMARY outcome

Timeframe: From date of randomization until the date of documented progression or date of death, whichever came first, approximately 1 year.

Population: Intent To Treat population. Only applies to the "olaparib alone" arm.

Outcome measures

Outcome measures
Measure	A - Olaparib Alone n=23 Participants Twice daily oral Olaparib 300mg alone as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. Olaparib Oral Product: olaparib 300mg twice daily
Efficacy of Olaparib Alone as Assessed by PFS (Progression-free Survival) Reported as Events Per Month	0.18 events/month Interval 0.11 to 0.27

PRIMARY outcome

Timeframe: From date of randomization until the date of documented progression or date of death, whichever came first, approximately 1 year.

Population: Intent to Treat population. Only applies to the "olaparib plus durvalumab" arm.

PFS, as defined as the time from randomization to the first occurrence of disease progression (as determined using RECIST v1.1 criteria and assessed by the investigator) or death from any cause on study for olaparib in combination with durvalumab. Death on study is defined as death from any cause within 30 days of the last dose of study treatment regimen. Reported as (disease progression or death) events per month.

Outcome measures

Outcome measures
Measure	A - Olaparib Alone n=22 Participants Twice daily oral Olaparib 300mg alone as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. Olaparib Oral Product: olaparib 300mg twice daily
Efficacy of Olaparib in Combination With Durvalumab as Assessed by PFS (Progression-free Survival)	0.11 events/month Interval 0.07 to 0.19

SECONDARY outcome

Timeframe: From date of randomization until death or last patient contact, approximately 2 years

Population: Only applies to the "olaparib alone" arm.

To determine the efficacy of maintenance olaparib following platinum based chemotherapy as assessed by overall survival (OS).

Outcome measures

Outcome measures
Measure	A - Olaparib Alone n=23 Participants Twice daily oral Olaparib 300mg alone as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. Olaparib Oral Product: olaparib 300mg twice daily
Overall Survival (Olaparib Alone)	21.68 months Interval 7.69 to Did not observe enough death events among participants to estimate the upper limit of the 95% CI for median overall survival time.

SECONDARY outcome

Timeframe: From date of randomization until death or last patient contact, approximately 2 years

Population: Only applies to the "olaparib plus durvalumab" arm.

To determine the efficacy of maintenance olaparib in combination with durvalumab following platinum based chemotherapy as assessed by overall survival (OS).

Outcome measures

Outcome measures
Measure	A - Olaparib Alone n=22 Participants Twice daily oral Olaparib 300mg alone as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. Olaparib Oral Product: olaparib 300mg twice daily
Overall Survival (Olaparib in Combination With Durvalumab)	18.27 months Interval 8.18 to Did not observe enough death events among participants to estimate the upper limit of the 95% CI for median overall survival time.

SECONDARY outcome

Timeframe: Assessed every 8 weeks from date of randomization until documented disease progression or last patient contact, approximately 1 year

Population: Only applies to the "olaparib alone" arm.

To determine the efficacy of maintenance olaparib following platinum-based chemotherapy as assessed by overall response rate (ORR) based on RECIST 1.1 (Response Evaluation Criteria In Solid Tumors Criteria). Per RECIST v1.1 for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	A - Olaparib Alone n=23 Participants Twice daily oral Olaparib 300mg alone as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. Olaparib Oral Product: olaparib 300mg twice daily
Overall Response Rate (ORR) as Measured by Number of Participants Achieving Complete Response (CR) or Partial Response (PR) as Defined by RECIST 1.1 (Olaparib Alone)	5 Participants

SECONDARY outcome

Timeframe: Assessed every 8 weeks from date of randomization until documented disease progression or last patient contact, approximately 1 year

Population: Only applies to the "olaparib plus durvalumab" arm.

To determine the efficacy of maintenance olaparib in combination with durvalumab following platinum-based chemotherapy as assessed by overall response rate (ORR) based on RECIST 1.1 (Response Evaluation Criteria In Solid Tumors Criteria). Per RECIST v1.1 for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	A - Olaparib Alone n=22 Participants Twice daily oral Olaparib 300mg alone as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. Olaparib Oral Product: olaparib 300mg twice daily
Overall Response Rate (ORR) as Measured by Number of Participants Achieving Complete Response (CR) or Partial Response (PR) as Defined by RECIST 1.1 (Olaparib in Combination With Durvalumab)	3 Participants

SECONDARY outcome

Timeframe: Assessed every 8 weeks from date of randomization until documented disease progression or last patient contact, approximately 1 year

Population: Only applies to the "olaparib alone" arm.

To determine the efficacy of maintenance olaparib following platinum-based chemotherapy as assessed by clinical benefit rate (CBR) based on RECIST 1.1 (Response Evaluation Criteria In Solid Tumors Criteria). Per RECIST v1.1 for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD); Clinical Benefit (CB) = CR + PR + SD for \>= 24 weeks.

Outcome measures

Outcome measures
Measure	A - Olaparib Alone n=23 Participants Twice daily oral Olaparib 300mg alone as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. Olaparib Oral Product: olaparib 300mg twice daily
Clinical Benefit Rate (CBR) as Measured by the Number of Participants Achieving Complete Response (CR), Partial Response (PR) or Stable Disease for ≥ 24 Weeks (SD) as Defined by RECIST 1.1. (Olaparib Alone)	9 Participants

SECONDARY outcome

Timeframe: Assessed every 8 weeks from date of randomization until documented disease progression or last patient contact, approximately 1 year

Population: Only applies to the "olaparib plus durvalumab" arm.

To determine the efficacy of maintenance olaparib in combination with durvalumab following platinum-based chemotherapy as assessed by clinical benefit rate (CBR) based on RECIST 1.1 (Response Evaluation Criteria In Solid Tumors Criteria). Per RECIST v1.1 for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD); Clinical Benefit (CB) = CR + PR + SD for \>= 24 weeks.

Outcome measures

Outcome measures
Measure	A - Olaparib Alone n=22 Participants Twice daily oral Olaparib 300mg alone as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. Olaparib Oral Product: olaparib 300mg twice daily
Clinical Benefit Rate (CBR) as Measured by the Number of Participants Achieving Complete Response (CR), Partial Response (PR) or Stable Disease for ≥ 24 Weeks (SD) as Defined by RECIST 1.1. (Olaparib in Combination With Durvalumab)	8 Participants

Adverse Events

A - Olaparib Alone

Serious events: 2 serious events

Other events: 23 other events

Deaths: 11 deaths

B - Olaparib Plus Durvalumab

Serious events: 3 serious events

Other events: 21 other events

Deaths: 8 deaths

Serious adverse events

Serious adverse events
Measure	A - Olaparib Alone n=23 participants at risk Twice daily oral Olaparib 300mg alone as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. Olaparib Oral Product: olaparib 300mg twice daily	B - Olaparib Plus Durvalumab n=22 participants at risk Twice daily oral olaparib plus intravenous Durvalumab every 4 weeks as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. Olaparib Oral Product in combination with Durvalumab: olaparib 300mg twice daily plus intravenous durvalumab every 28 days
General disorders Pyrexia	0.00% 0/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	9.1% 2/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Gastrointestinal disorders Nausea	0.00% 0/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	4.5% 1/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Gastrointestinal disorders Vomiting	0.00% 0/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	4.5% 1/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Infections and infestations Pneumonia	0.00% 0/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	4.5% 1/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Investigations Neutrophil count decreased	0.00% 0/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	4.5% 1/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour associated fever	4.3% 1/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	0.00% 0/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Respiratory, thoracic and mediastinal disorders Pneumothorax	4.3% 1/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	0.00% 0/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years

Other adverse events

Additional Information

Senior Biostatistician

Duke Clinical Research Institute

Phone: 919-668-8052

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	A - Olaparib Alone n=23 participants at risk Twice daily oral Olaparib 300mg alone as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. Olaparib Oral Product: olaparib 300mg twice daily	B - Olaparib Plus Durvalumab n=22 participants at risk Twice daily oral olaparib plus intravenous Durvalumab every 4 weeks as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. Olaparib Oral Product in combination with Durvalumab: olaparib 300mg twice daily plus intravenous durvalumab every 28 days
Gastrointestinal disorders Nausea	56.5% 13/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	40.9% 9/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
General disorders Fatigue	52.2% 12/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	27.3% 6/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Blood and lymphatic system disorders Anaemia	39.1% 9/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	31.8% 7/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Metabolism and nutrition disorders Decreased appetite	26.1% 6/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	40.9% 9/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Gastrointestinal disorders Vomiting	21.7% 5/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	31.8% 7/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Nervous system disorders Dizziness	26.1% 6/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	22.7% 5/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Gastrointestinal disorders Diarrhoea	17.4% 4/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	22.7% 5/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Investigations Neutrophil count decreased	21.7% 5/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	18.2% 4/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Respiratory, thoracic and mediastinal disorders Cough	8.7% 2/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	31.8% 7/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Nervous system disorders Headache	8.7% 2/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	27.3% 6/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
General disorders Mucosal inflammation	17.4% 4/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	13.6% 3/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Gastrointestinal disorders Constipation	17.4% 4/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	9.1% 2/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Nervous system disorders Peripheral sensory neuropathy	8.7% 2/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	18.2% 4/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Respiratory, thoracic and mediastinal disorders Dyspnoea	13.0% 3/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	13.6% 3/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Investigations Platelet count decreased	8.7% 2/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	13.6% 3/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Musculoskeletal and connective tissue disorders Arthralgia	8.7% 2/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	13.6% 3/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Psychiatric disorders Insomnia	13.0% 3/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	9.1% 2/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Skin and subcutaneous tissue disorders Rash	13.0% 3/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	9.1% 2/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
General disorders Pain	8.7% 2/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	9.1% 2/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
General disorders Pyrexia	4.3% 1/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	13.6% 3/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Investigations White blood cell count decreased	8.7% 2/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	9.1% 2/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Metabolism and nutrition disorders Hypoalbuminaemia	4.3% 1/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	13.6% 3/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Blood and lymphatic system disorders Neutropenia	8.7% 2/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	4.5% 1/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Gastrointestinal disorders Dry mouth	0.00% 0/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	13.6% 3/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Gastrointestinal disorders Dyspepsia	8.7% 2/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	4.5% 1/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
General disorders Influenza like illness	4.3% 1/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	9.1% 2/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
General disorders Non-cardiac chest pain	4.3% 1/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	9.1% 2/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Infections and infestations Pneumonia	8.7% 2/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	4.5% 1/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Investigations Blood creatinine increased	13.0% 3/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	0.00% 0/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Metabolism and nutrition disorders Hypokalaemia	4.3% 1/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	9.1% 2/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Endocrine disorders Hypothyroidism	0.00% 0/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	9.1% 2/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Gastrointestinal disorders Oral pain	0.00% 0/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	9.1% 2/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
General disorders Chills	0.00% 0/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	9.1% 2/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Investigations Alanine aminotransferase increased	8.7% 2/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	0.00% 0/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Metabolism and nutrition disorders Hyponatraemia	8.7% 2/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	0.00% 0/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	9.1% 2/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Musculoskeletal and connective tissue disorders Pain in extremity	8.7% 2/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	0.00% 0/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	9.1% 2/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	9.1% 2/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years
Vascular disorders Hypertension	8.7% 2/23 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years	0.00% 0/22 • From the first dose of either study drug through 30 days after the last dose of either study drug or until the initiation of an alternative anticancer therapy, up to 2 years