A Combination Study of Rucaparib and Atezolizumab in Participants With Advanced Gynecologic Cancers and Triple-Negative Breast Cancer

Roche

Status and phase: Completed; Phase 1

Conditions: Gynecologic Neoplasms

Treatments: Drug: Atezolizumab; Drug: Rucaparib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03101280

WO39409

2016-002610-47 (EudraCT Number)

Details and patient eligibility

About

This is a Phase Ib, open-label, non-randomized study in patients with previously treated advanced ovarian or endometrial cancer (Part 1) and platinum-sensitive ovarian cancer or triple-negative breast cancer (TNBC) (Part 2) to investigate the dose, safety, pharmacokinetics, and preliminary efficacy of rucaparib in combination with atezolizumab. The study is conducted in 2 parts: a Dose-Finding Phase (Part 1) and a Dose-Expansion Phase (Part 2)

Enrollment: 29 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• A life expectancy of at least 3 months
• Have disease that is measurable as according to RECIST v1.1
• Have sufficient archival formalin-fixed paraffin-embedded (FFPE) tumor tissue available for planned analyses
• For Part 1, have a histologically confirmed diagnosis of ovarian or endometrial cancer, and have received at least one line of prior therapy for metastatic disease
• For Part 2 ONLY, have disease that can be safely biopsied
• For Part 2 ONLY, have a deleterious germline or somatic breast cancer susceptibility gene 1 (BRCA1) or BRCA2 mutation or tumors that are wild-type BRCA but show high levels of loss of heterozygosity (LOH) (tBRCAwt/LOHhigh) signature
• For Part 2 Cohort 1 (ovarian cancer), high-grade serous or Grade 3 endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer (PPC)
• For Part 2 Cohort 1, have received at least one and no more than two lines of prior platinum-containing therapy and progressed after the most recent platinum therapy in a platinum-sensitive timeframe
• For Part 2 ONLY, Cohort 1, have a CA125 measurement that is greater than 2 times the upper limit of normal (ULN)
• For Part 2 Cohort 2 (TNBC), metastatic, histologically confirmed estrogen receptor (ER)-negative, progesterone receptor-negative, and HER2-negative adenocarcinoma of the breast per local laboratory assessment
• For Part 2 Cohort 2, radiologic/objective evidence of recurrence or disease progression after one line of chemotherapy for TNBC in the metastatic setting
• Have adequate organ function

Exclusion criteria

• History of prior malignancy except a) curatively treated non-melanoma skin cancer, b) solid tumor treated curatively more than 3 years ago without evidence of recurrence, c) For Cohort 1 (ovarian cancer): breast cancer with no evidence of disease or inactive for at least 3 years, and d) synchronous endometrial cancer (Stage 1A) with ovarian cancer
• Treatment with chemotherapy, radiation, hormones (except corticosteroids and megestrol acetate), or other anticancer therapies less than or equal to (<=) 14 days prior to first dose of study treatment
• Preexisting duodenal stent and/or any gastrointestinal disorder or defect that would, in the opinion of the investigator, interfere with absorption of rucaparib
• Symptomatic and/or untreated central nervous system metastases
• Prior treatment with any poly adenosine diphosphate-ribose polymerase (PARP) inhibitor

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

29 participants in 2 patient groups

Dose-Finding Phase (Part 1): Rucaparib and Atezolizumab

Experimental group

Description:

Approximately 6-18 participants with advanced gynecological cancers will receive different doses of rucaparib administered orally (PO) twice daily (BID) with a fixed dose of atezolizumab (1200 milligrams \[mg\] intravenously \[IV\], every 21 days) in 21-day cycles, starting with 400 mg rucaparib BID. The recommended Phase II dose (RP2D), determined by the highest dose level with an acceptable safety profile and with a minimum of 6 participants at which fewer than one-third of participants experience a DLT, was identified as 600 mg rucaparib twice a day (BID).

Treatment:

Drug: Rucaparib

Drug: Atezolizumab

Dose-Expansion Phase (Part 2): Rucaparib and Atezolizumab

Experimental group

Description:

Two tumor-specific expansion cohorts will begin treatment with a 21-day run-in period of rucaparib monotherapy at the specified dose for rucaparib in the potential RP2D identified in Part 1 for the combination. Cohort 1 will have approximately 30 participants with advanced, platinum-sensitive ovarian cancer with tumors harboring a tBRCA mutation \[tBCRA(mut)\] or BRCA-like molecular signature \[tBRCA(wt)/LOH(high)\]. Cohort 2 will have approximately 20 participants with previously treated triple-negative breast cancer (TNBC) with a tBRCA mutation \[tBCRA(mut)\] or BRCA-like molecular signature \[tBRCA(wt)/LOH(high)\] and have not been exposed to cancer immunotherapies. Following the run in period, participants will receive the combination of rucaparib (specified dose, BID) and atezolizumab (1200 mg IV, every 21 days) in 21-day cycles.

Treatment:

Drug: Rucaparib

Drug: Atezolizumab