Efficacy and Safety of the Combination of Rucaparib (PARP Inhibitor) and Atezolizumab (Anti-PD-L1 Antibody) in Patients With DNA Repair-deficient or Platinum-sensitive Solid Tumors

NCT04276376 | Terminated Phase 2 DMC

• 2 other identifiers: 2018-001744-622018/2727
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the trial is to evaluate the antitumor activity of atezolizumab and rucaparib in patients with selected advanced solid tumors as measured by the Overall Response Rate

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  at 12 weeks

Study Arms (4)

Cohort 1A-D

EXPERIMENTAL

Molecularly selected cohorts that harbor DNA repair deficiency, defined as bi-allelic loss-of-function alteration (mutation and/or deletion) in at least one of the following genes: ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, PALB2, RAD51C, RAD51D, FANCA, NBN, RAD51, RAD54L. 1.A - Non-Small Cell Lung Cancer 1.B - Urothelial Bladder Cancer 1.C - metastatic Castration Resistant Prostate Cancer 1.D - others: any histology, excepted breast cancer or serous ovarian cancer

Drug: Atezolizumab; Drug: Rucaparib

Cohort 2A-C

EXPERIMENTAL

Platinum-sensitive disease 2.A - Non-Small Cell Lung Cancer 2.B - Urothelial Bladder Cancer 2.C - Gastric or gastro-esophageal junction adenocarcinoma

Drug: Atezolizumab; Drug: Rucaparib

Cohort 3

EXPERIMENTAL

Metastatic Castration Resistant Prostate Cancer (mCRPC)

Drug: Atezolizumab; Drug: Rucaparib

Cohort 4

EXPERIMENTAL

Clear Cell Renal Cell Carcinoma

Drug: Atezolizumab; Drug: Rucaparib

Interventions

Atezolizumab DRUG

Fc-engineered, humanized, Ig G1 monoclonal antibody against PDL-1 1200mg q3w

Cohort 1A-D; Cohort 2A-C; Cohort 3; Cohort 4

Rucaparib DRUG

Inhibitor of poly-adenosine diphosphate \[ADP\] ribose polymerase (PARP) 600mg BID

Cohort 1A-D; Cohort 2A-C; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form.
• Age ≥ 18 years.
• Patients must have histologically or cytologically confirmed progressive metastatic or recurrent solid tumor (as defined below for each tumor type). Diagnosis must be stated in a pathology report and confirmed by the investigator.
• To be enrolled in this study, only the tumor types and settings described below are allowed:
• Cohorts 1 A-D: DNA repair deficiency, defined as bi-allelic loss-of-function alteration (mutation and/or deletion) in at least one of the following genes: ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, PALB2, RAD51C, RAD51D, FANCA, NBN, RAD51, RAD54L.
• Cohort 1A: Non Small Cell Lung Cancer 4.1.2 - Cohort 1B: Urothelial Bladder Cancer 4.1.3 - Cohort 1C: metastatic Castration Resistant Prostate Cancer (mCRPC) 4.1.4 - Cohort 1D: Others 4.2 - Cohorts 2A-C: Platinum-sensitive disease 4.2.1 - Cohort 2A: Non Small Cell Lung Cancer 4.2.2 - Cohort 2B: Urothelial Bladder Cancer 4.2.3 - Cohort 2C: Gastric or gastro-esophageal junction adenocarcinoma 4.3 - Cohort 3: Metastatic Castration Resistant Prostate Cancer (mCRPC) 4.4 - Cohort 4: Clear cell Renal Cell Carcinoma
• Representative archival formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (preferred) or 20 freshly cut and unstained slides, with an associated pathology report, for ancillary studies and central testing, is mandatory for all cohorts. In all cases, recovery of the most recent tumor block or biopsy is encouraged and tumor tissue has to date back from less than 3 years ago (less than 6 years for cohort 4). Cohorts 1 and 2: if tumor tissue is more than 3 years old, a fresh tumor biopsy is mandatory. Cohort 4: if tumor tissue is more than 6 years old, a fresh tumor biopsy is mandatory.
• Specificities for Cohorts 1A-D:
• If no archival tissue is available or if tumor tissue is more than 3 years old, feasibility of a fresh tumor biopsy at baseline (C0D1 pre-dose) should be ensured and mutation confirmed on that tissue for cohorts 1A, 1B and 1D. Only tissue from core needle, punch or excisional biopsy sample collection will be accepted. Other methods such as fine-needle aspiration, brushing, bone tissue or lavage samples are not acceptable.
• Bone biopsies are allowed for mCRPC (cohort 1C), if sufficient tumor cellularity can be achieved.
• Specificity for cohort 3:
• If no archival tumor biopsy is available, a new fresh biopsy should be done prior to treatment start (C0D1 pre-dose) whenever feasible; otherwise, any archival tumor tissue will be accepted.
• Core or excisional biopsy from soft tissue or a bone biopsy is required from a site not previously irradiated (samples from tumors progressing in a prior site of radiation are allowed; other exceptions may be considered after Sponsor consultation).
• Measurable disease, defined as:
• For the non-prostate cohorts: At least one lesion, not previously irradiated, measurable according to RECIST v1.1 as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and suitable for repeated assessment.

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead

Study Sites (1)

Gustave Roussy

Villejuif, Val De Marne, 94800, France

Location

MeSH Terms

Interventions

atezolizumab; rucaparib

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2020
• First Posted: February 19, 2020
• Study Start: April 12, 2019
• Primary Completion: January 25, 2023
• Study Completion: December 12, 2023
• Last Updated: December 1, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)