Trial Outcomes & Findings for A Study Evaluating the Safety, Pharmacokinetics and Efficacy of Ipatasertib Administered in Combination With Rucaparib in Participants With Advanced Breast, Ovarian Cancer, and Prostate Cancer. (NCT NCT03840200)

Last Updated: 2023-10-30

Results Overview

An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

51 participants

Primary outcome timeframe

From Baseline up until 90 days after the last dose of study drug (up to 2 years)

Results posted on

2023-10-30

Participant Flow

Participants took part in the study at 14 investigative sites in 5 countries (Australia, Italy, the Republic of Korea, Spain, and the United States) from 12 June 2019 to 04 January 2022.

A total of 78 participants were screened. Enrollment in Cohort 3 was not opened as one-third of Dose Limiting Toxicity (DLT) evaluable participants receiving the highest dose of rucaparib in Cohort 2a experienced a DLT.

Participant milestones

Participant milestones
Measure	Dose Escalation-Cohort 1 Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 milligrams (mg), orally, once daily (QD) for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 400 mg, orally twice daily (BID) in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2a Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 600 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2b Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 400 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 400 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Expansion Participants with advanced prostate cancer received ipatasertib, 400 mg, orally QD and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator decision to withdraw, whichever occurred first.
Overall Study STARTED	8	6	7	30
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	8	6	7	30

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose Escalation-Cohort 1 Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 milligrams (mg), orally, once daily (QD) for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 400 mg, orally twice daily (BID) in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2a Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 600 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2b Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 400 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 400 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Expansion Participants with advanced prostate cancer received ipatasertib, 400 mg, orally QD and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator decision to withdraw, whichever occurred first.
Overall Study Death	6	3	6	10
Overall Study Reason Not Specified	2	2	1	15
Overall Study Physician Decision	0	0	0	2
Overall Study Progressive Disease	0	0	0	1
Overall Study Withdrawal by Subject	0	1	0	2

Baseline Characteristics

A Study Evaluating the Safety, Pharmacokinetics and Efficacy of Ipatasertib Administered in Combination With Rucaparib in Participants With Advanced Breast, Ovarian Cancer, and Prostate Cancer.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Escalation-Cohort 1 n=8 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2a n=6 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 600 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2b n=7 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 400 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 400 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Expansion n=30 Participants Participants with advanced prostate cancer received ipatasertib, 400 mg, orally QD and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator decision to withdraw, whichever occurred first.	Total n=51 Participants Total of all reporting groups
Age, Continuous	68.3 years STANDARD_DEVIATION 4.7 • n=5 Participants	65.2 years STANDARD_DEVIATION 6.0 • n=7 Participants	69.3 years STANDARD_DEVIATION 5.9 • n=5 Participants	69.1 years STANDARD_DEVIATION 9.2 • n=4 Participants	68.5 years STANDARD_DEVIATION 7.8 • n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants	30 Participants n=4 Participants	47 Participants n=21 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	8 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	28 Participants n=4 Participants	48 Participants n=21 Participants
Race/Ethnicity, Customized Not Stated	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants	4 Participants n=21 Participants
Race/Ethnicity, Customized White	8 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	26 Participants n=4 Participants	46 Participants n=21 Participants

PRIMARY outcome

Timeframe: From Baseline up until 90 days after the last dose of study drug (up to 2 years)

Population: Safety population included all participants who were treated with at least one dose of the study treatment.

Outcome measures

Outcome measures
Measure	Dose Escalation-Cohort 1 n=8 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2a n=6 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 600 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2b n=7 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 400 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 400 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Expansion n=30 Participants Participants with advanced prostate cancer received ipatasertib, 400 mg, orally QD and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator decision to withdraw, whichever occurred first.
Percentage of Participants With Adverse Events	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants

PRIMARY outcome

Timeframe: Day -7 to Day 28 of Cycle 1 (1 cycle = 28 days) (up to 35 days)

Population: Safety population included all participants who were treated with at least one dose of the study treatment. Results for dose expansion is not presented.

A DLT was defined as adverse events related to study treatments occurring during the DLT reporting period, which included: any death related to study treatment; grade 4 neutropenia lasting for ≥7 days; grade ≥3 neutropenia complicated by fever ≥38°C or infection; grade 4 thrombocytopenia lasting for ≥7 days; grade ≥3 thrombocytopenia complicated by hemorrhage or that requires transfusion; study treatment-related grade ≥3 non-hematologic toxicity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5 (NCI CTCAE, v5.0).

Outcome measures

Outcome measures
Measure	Dose Escalation-Cohort 1 n=8 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2a n=6 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 600 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2b n=7 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 400 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 400 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Expansion Participants with advanced prostate cancer received ipatasertib, 400 mg, orally QD and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator decision to withdraw, whichever occurred first.
Dose Escalation: Percentage of Participants With Dose-Limiting Toxicities (DLTs) That Determine the Maximum-Tolerated Dose (MTD) of the Ipatasertib and Rucaparib Combination	12.5 percentage of participants	33.3 percentage of participants	0 percentage of participants	—

PRIMARY outcome

Timeframe: From Baseline up to 1.5 years

Population: Efficacy-evaluable population included all participants who had prostate cancer, baseline lesion, and received actual dosing equivalent to the planned dose of treatment. Number of participants analyzed are participants with data available for analysis.

PSA response was defined as the percentage of participants with a reduction in the PSA level of 50% or more. PSA response analysis was based on central PSA measurement. The 95% CI was estimated using the Clopper-Pearson method.

Outcome measures

Outcome measures
Measure	Dose Escalation-Cohort 1 n=4 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2a n=3 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 600 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2b n=4 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 400 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 400 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Expansion n=26 Participants Participants with advanced prostate cancer received ipatasertib, 400 mg, orally QD and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator decision to withdraw, whichever occurred first.
Percentage of Participants With Prostate-Specific Antigen Response (PSAR)	0 percentage of participants Interval 0.0 to 60.24	33.3 percentage of participants Interval 0.84 to 90.57	25.0 percentage of participants Interval 0.63 to 80.59	23.1 percentage of participants Interval 8.97 to 43.65

SECONDARY outcome

Timeframe: From Baseline up to 1.5 years (assessed at the end of Cycle 2,4,6, and every 3 cycles thereafter up to progression, 1 cycle= 28 days)

Objective response rate (ORR), defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) on two consecutive occasions ≥4 weeks apart, as determined by the investigator per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v.1.1). A complete response was defined as the disappearance of all lesions. Pathological lymph nodes (whether target or non-target) must have a reduction in short axis to less than 10 millimeters (mm). A partial response was defined as ≥30% decrease in the sum of the diameter of target lesions, in the absence of CR persistence of one or more non-target lesions. The analysis is based on the subset of participants with measurable lesions as per RECIST criteria at baseline. ORR was calculated, and the 95% CI was estimated using the Clopper-Pearson method.

Outcome measures

Outcome measures
Measure	Dose Escalation-Cohort 1 n=2 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2a n=1 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 600 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2b n=6 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 400 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 400 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Expansion n=15 Participants Participants with advanced prostate cancer received ipatasertib, 400 mg, orally QD and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator decision to withdraw, whichever occurred first.
Percentage of Participants With Objective Response, as Assessed by Investigator Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v.1.1)	0 percentage of participants Interval 0.0 to 84.19	0 percentage of participants Interval 0.0 to 97.5	0 percentage of participants Interval 0.0 to 45.93	13.3 percentage of participants Interval 1.66 to 40.46

SECONDARY outcome

Timeframe: From Baseline up to 1.5 years (assessed at the end of Cycle 2,4,6, and every 3 cycles thereafter up to progression, 1 cycle= 28 days)

Population: Intent-to-treat population included all participants who were treated with at least one dose of the study treatment. Number of participants analyzed is the number of participants with confirmed objective response.

DOR was defined as the time from the first occurrence of a documented objective response until the time of documented disease progression or death from any cause during the study, whichever occurred first. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and an absolute increase of at least 5 mm, or the presence of new lesions. The duration of response was estimated by Kaplan-Meier. 95% CI for median was computed using the method of Brookmeyer and Crowley.

Outcome measures

Outcome measures
Measure	Dose Escalation-Cohort 1 n=2 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2a Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 600 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2b Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 400 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 400 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Expansion Participants with advanced prostate cancer received ipatasertib, 400 mg, orally QD and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator decision to withdraw, whichever occurred first.
Duration of Objective Response in Participants With Measurable Disease at Baseline, as Assessed by Investigator Based on RECIST v1.1	NA months Median upper and limit of 95% CI was not estimable due to insufficient number of participants with events.	—	—	—

SECONDARY outcome

Timeframe: From Baseline up to 1.5 years (assessed at the end of Cycle 2,4,6, and every 3 cycles thereafter up to progression, 1 cycle= 28 days)

Population: Efficacy-evaluable population included all participants who had prostate cancer, baseline lesion, and received actual dosing equivalent to the planned dose of treatment.

rPFS was defined as the time from study treatment initiation to the first occurrence of documented disease progression, as assessed by the investigator with the use of the PCWG3 criteria (soft tissue: Progressive disease on computed tomography \[CT\] or MRI scans according to RECIST v1.1, and bone metastasis by bone scan according to the PCWG3 criteria) or death from any cause, whichever occurred first. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and an absolute increase of at least 5 mm, or the presence of new lesions. Kaplan-Meier method was used to estimate the median. 95% CI for median was computed using the method of Brookmeyer and Crowley.

Outcome measures

Outcome measures
Measure	Dose Escalation-Cohort 1 n=6 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2a n=4 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 600 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2b n=7 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 400 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 400 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Expansion n=28 Participants Participants with advanced prostate cancer received ipatasertib, 400 mg, orally QD and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator decision to withdraw, whichever occurred first.
Radiographic Progression Free Survival (rPFS), as Assessed by Prostate Cancer Working Group 3 Criteria (PCWG3)	11.0 months Interval 9.8 to Upper limit of 95% CI was not estimable due to insufficient number of participants with events.	3.0 months Interval 1.9 to Upper limit of 95% CI was not estimable due to insufficient number of participants with events.	5.1 months Interval 2.1 to 11.2	7.2 months Interval 4.0 to 10.9

SECONDARY outcome

Timeframe: From Baseline to death from any cause, assessed up to 2 years

Population: Efficacy-evaluable population included all participants who had prostate cancer, baseline lesion, and received actual dosing equivalent to the planned dose of treatment.

OS was defined as the time from study treatment initiation to the time of death due to any cause. Kaplan-Meier method was used to estimate the median. 95% CI for median was computed using the method of Brookmeyer and Crowley.

Outcome measures

Outcome measures
Measure	Dose Escalation-Cohort 1 n=6 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2a n=4 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 600 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2b n=7 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 400 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 400 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Expansion n=28 Participants Participants with advanced prostate cancer received ipatasertib, 400 mg, orally QD and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator decision to withdraw, whichever occurred first.
Overall Survival (OS) in All Participants	20.8 months Interval 14.4 to Upper limit of 95% CI was not estimable due to insufficient number of participants with events.	13.8 months Interval 4.8 to Upper limit of 95% CI was not estimable due to insufficient number of participants with events.	13.3 months Interval 9.9 to Upper limit of 95% CI was not estimable due to insufficient number of participants with events.	NA months Interval 10.9 to Upper limit of 95% CI was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Dose Escalation: Cycle 1: Day 1 and 15 (1, 2 ,3, 5 hours post-dose), Day 15 (Predose) and Cycle 2: Day 1 and 15 (Predose); Dose Expansion: Cycle 1: Day 15 (Predose) and Cycle 2: Day 1 and 15 (Predose) (1 cycle = 28 days)

Population: PK-evaluable population includes all participants who had at least one evaluable PK sample. Number analyzed is the number of participants with data available for analysis at the specified time point.

Outcome measures

Outcome measures
Measure	Dose Escalation-Cohort 1 n=8 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2a n=6 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 600 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2b n=7 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 400 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 400 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Expansion n=30 Participants Participants with advanced prostate cancer received ipatasertib, 400 mg, orally QD and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator decision to withdraw, whichever occurred first.
Plasma Concentration of Ipatasertib Cycle 1 Day 15:2 hour post dose	98.7 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 98.0	177 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 119.3	177 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 51.3	—
Plasma Concentration of Ipatasertib Cycle 1 Day 15:3hour post dose	92.4 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 53.2	141 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 108.7	181 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 43.1	—
Plasma Concentration of Ipatasertib Cycle 1 Day 1:1 hour post dose	160 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 262.1	172 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 89.2	192 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 106.0	—
Plasma Concentration of Ipatasertib Cycle 1 Day 1:2 hour post dose	159 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 59.0	133 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 77.7	230 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 44.7	—
Plasma Concentration of Ipatasertib Cycle 1 Day 1:3 hour post dose	116 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 85.7	131 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 49.0	249 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 24.5	—
Plasma Concentration of Ipatasertib Cycle 1 Day 1:5 hour post dose	93.4 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 52.9	127 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 58.4	171 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 23.9	—
Plasma Concentration of Ipatasertib Cycle 1 Day 15: Predose	21.6 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 57.1	39.4 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 178.4	33.5 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 29.5	48.4 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 96.6
Plasma Concentration of Ipatasertib Cycle 1 Day 15:1 hour post dose	130 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 126.3	242 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 100.8	158 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 94.8	—
Plasma Concentration of Ipatasertib Cycle 1 Day 15:5 hour post dose	85.1 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 28.7	105 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 126.1	172 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 33.1	—
Plasma Concentration of Ipatasertib Cycle 2 Day 1: Predose	19.2 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 108.1	20.9 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 51.3	40.1 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 33.2	31.2 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 226.3
Plasma Concentration of Ipatasertib Cycle 2 Day 15: Predose	18.9 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 72.6	31.1 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 78.0	49.4 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 43.5	48.6 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 77.2

SECONDARY outcome

Outcome measures

Outcome measures
Measure	Dose Escalation-Cohort 1 n=8 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2a n=6 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 600 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2b n=7 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 400 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 400 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Expansion n=30 Participants Participants with advanced prostate cancer received ipatasertib, 400 mg, orally QD and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator decision to withdraw, whichever occurred first.
Plasma Concentration of Ipatasertib's Metabolite (G-037720) Cycle 1 Day 1:5 hour post dose	44.0 ng/mL Geometric Coefficient of Variation 53.3	85.3 ng/mL Geometric Coefficient of Variation 54.3	112 ng/mL Geometric Coefficient of Variation 32.2	—
Plasma Concentration of Ipatasertib's Metabolite (G-037720) Cycle 1 Day 15: Predose	11.8 ng/mL Geometric Coefficient of Variation 25.0	23.7 ng/mL Geometric Coefficient of Variation 128.8	20.2 ng/mL Geometric Coefficient of Variation 21.4	25.7 ng/mL Geometric Coefficient of Variation 103.2
Plasma Concentration of Ipatasertib's Metabolite (G-037720) Cycle 1 Day 15:1 hour post dose	38.0 ng/mL Geometric Coefficient of Variation 111.9	67.4 ng/mL Geometric Coefficient of Variation 35.8	56.1 ng/mL Geometric Coefficient of Variation 104.8	—
Plasma Concentration of Ipatasertib's Metabolite (G-037720) Cycle 1 Day 15:2 hour post dose	43.2 ng/mL Geometric Coefficient of Variation 85.9	76.3 ng/mL Geometric Coefficient of Variation 55.4	65.0 ng/mL Geometric Coefficient of Variation 69.0	—
Plasma Concentration of Ipatasertib's Metabolite (G-037720) Cycle 1 Day 1:1 hour post dose	65.0 ng/mL Geometric Coefficient of Variation 187.1	81.1 ng/mL Geometric Coefficient of Variation 81.1	82.0 ng/mL Geometric Coefficient of Variation 119.3	—
Plasma Concentration of Ipatasertib's Metabolite (G-037720) Cycle 1 Day 1:2 hour post dose	71.2 ng/mL Geometric Coefficient of Variation 51.7	92.7 ng/mL Geometric Coefficient of Variation 70.6	115 ng/mL Geometric Coefficient of Variation 53.0	—
Plasma Concentration of Ipatasertib's Metabolite (G-037720) Cycle 1 Day 1:3 hour post dose	57.8 ng/mL Geometric Coefficient of Variation 62.2	85.0 ng/mL Geometric Coefficient of Variation 46.2	141 ng/mL Geometric Coefficient of Variation 42.8	—
Plasma Concentration of Ipatasertib's Metabolite (G-037720) Cycle 1 Day 15:3 hour post dose	38.5 ng/mL Geometric Coefficient of Variation 62.8	65.8 ng/mL Geometric Coefficient of Variation 61.9	75.9 ng/mL Geometric Coefficient of Variation 56.8	—
Plasma Concentration of Ipatasertib's Metabolite (G-037720) Cycle 1 Day 15: 5 hour post dose	33.0 ng/mL Geometric Coefficient of Variation 42.8	53.3 ng/mL Geometric Coefficient of Variation 81.9	73.4 ng/mL Geometric Coefficient of Variation 34.3	—
Plasma Concentration of Ipatasertib's Metabolite (G-037720) Cycle 2 Day 1: Predose	10.3 ng/mL Geometric Coefficient of Variation 58.0	13.9 ng/mL Geometric Coefficient of Variation 62.9	22.4 ng/mL Geometric Coefficient of Variation 35.1	16.3 ng/mL Geometric Coefficient of Variation 131.2
Plasma Concentration of Ipatasertib's Metabolite (G-037720) Cycle 2 Day 15: Predose	11.3 ng/mL Geometric Coefficient of Variation 29.9	19.7 ng/mL Geometric Coefficient of Variation 99.6	26.4 ng/mL Geometric Coefficient of Variation 38.8	23.6 ng/mL Geometric Coefficient of Variation 75.4

SECONDARY outcome

Timeframe: Cycle 1 Day 15 and Cycle 2 Day 1 and 15: Predose (1 cycle = 28 days)

Population: PK-evaluable population included all participants who had at least one evaluable PK sample. Number analyzed is the number of participants with data available for analysis at the specified time point.

Outcome measures

Outcome measures
Measure	Dose Escalation-Cohort 1 n=8 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2a n=6 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 600 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2b n=7 Participants Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 400 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 400 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Expansion n=30 Participants Participants with advanced prostate cancer received ipatasertib, 400 mg, orally QD and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator decision to withdraw, whichever occurred first.
Plasma Concentration of Rucaparib Cycle 1 Day 15: Predose	775 ng/mL Geometric Coefficient of Variation 102.3	3130 ng/mL Geometric Coefficient of Variation 142.5	994 ng/mL Geometric Coefficient of Variation 57.2	1660 ng/mL Geometric Coefficient of Variation 64.8
Plasma Concentration of Rucaparib Cycle 2 Day 1: Predose	631 ng/mL Geometric Coefficient of Variation 178.9	1660 ng/mL Geometric Coefficient of Variation 79.1	1050 ng/mL Geometric Coefficient of Variation 57.7	1210 ng/mL Geometric Coefficient of Variation 200.1
Plasma Concentration of Rucaparib Cycle 2 Day 15: Predose	1090 ng/mL Geometric Coefficient of Variation 51.4	263 ng/mL Geometric Coefficient of Variation 6165.7	1250 ng/mL Geometric Coefficient of Variation 48.3	975 ng/mL Geometric Coefficient of Variation 217.5

Adverse Events

Dose Escalation-Cohort 1

Serious events: 2 serious events

Other events: 8 other events

Deaths: 6 deaths

Dose Escalation-Cohort 2a

Serious events: 1 serious events

Other events: 6 other events

Deaths: 3 deaths

Dose Escalation-Cohort 2b

Serious events: 1 serious events

Other events: 7 other events

Deaths: 6 deaths

Dose Expansion

Serious events: 8 serious events

Other events: 30 other events

Deaths: 10 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Dose Escalation-Cohort 1 n=8 participants at risk Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2a n=6 participants at risk Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 300 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 300 mg, orally QD, and rucaparib, 600 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Escalation-Cohort 2b n=7 participants at risk Participants with advanced breast cancer, ovarian cancer, or prostate cancer received ipatasertib, 400 mg, orally, QD for 7 days in the run-in period. Participants then received ipatasertib, 400 mg, orally QD, and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator's decision to withdraw, whichever occurred first.	Dose Expansion n=30 participants at risk Participants with advanced prostate cancer received ipatasertib, 400 mg, orally QD and rucaparib, 400 mg, orally BID in each 28-day cycle until disease progression, unacceptable toxicity, death, or participant or investigator decision to withdraw, whichever occurred first.
Blood and lymphatic system disorders Anaemia	0.00% 0/8 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/6 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/7 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	3.3% 1/30 • Number of events 1 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/8 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/6 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/7 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	3.3% 1/30 • Number of events 1 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Vertigo	0.00% 0/8 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	16.7% 1/6 • Number of events 1 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/7 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/30 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain	0.00% 0/8 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/6 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/7 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	3.3% 1/30 • Number of events 1 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	12.5% 1/8 • Number of events 1 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/6 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/7 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/30 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastritis	0.00% 0/8 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/6 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/7 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	3.3% 1/30 • Number of events 1 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Intestinal obstruction	12.5% 1/8 • Number of events 1 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/6 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/7 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/30 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	0.00% 0/8 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/6 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/7 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	3.3% 1/30 • Number of events 1 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	0.00% 0/8 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/6 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/7 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	3.3% 1/30 • Number of events 1 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.
General disorders Fatigue	0.00% 0/8 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/6 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/7 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	3.3% 1/30 • Number of events 1 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.
Infections and infestations Enteritis infectious	12.5% 1/8 • Number of events 1 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/6 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/7 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/30 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.
Infections and infestations Urinary tract infection	0.00% 0/8 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	16.7% 1/6 • Number of events 2 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	14.3% 1/7 • Number of events 1 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/30 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.
Investigations Blood creatinine increased	12.5% 1/8 • Number of events 1 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/6 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/7 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/30 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Dehydration	0.00% 0/8 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/6 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/7 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	6.7% 2/30 • Number of events 2 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/8 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/6 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/7 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	3.3% 1/30 • Number of events 1 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.
Renal and urinary disorders Acute kidney injury	0.00% 0/8 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/6 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/7 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	3.3% 1/30 • Number of events 1 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.
Renal and urinary disorders Renal colic	0.00% 0/8 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/6 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/7 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	3.3% 1/30 • Number of events 1 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.5% 1/8 • Number of events 1 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/6 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/7 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/30 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/8 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/6 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	0.00% 0/7 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.	3.3% 1/30 • Number of events 1 • From Baseline up until 90 days after the last dose of study drug (up to 2 years) Safety population included all participants who received at least 1 dose of study drug.