152P - Efficacy of olaparib in advanced cancers with germline or somatic tumor mutations in BRCA1, BRCA2, CHEK2 and ATM: A Belgian precision tumor-agnostic phase II study

Background

The Belgian Precision initiative aims to maximize the implementation of tumor-agnostic NGS in patients with advanced cancer and enhance access to molecularly-guided treatment options (MGTOs). Academic tumor-agnostic basket phase 2 studies are part of this initiative. The current investigator-driven trial aimed to investigate olaparib efficacy in advanced cancers with a pathogenic or likely pathogenic mutation (germline or somatic) in a gene that plays a role in homologous recombination (HR).

Methods

Open-label multi-cohort phase 2 study that examines the efficacy of olaparib in patients with an HR gene mutation in their tumor and failed SoC. Patients with a somatic or germline mutation in the same gene define a cohort. For each cohort, a Simon minimax two-stage design was used. If a response was observed in the first 13 patients, 14 additional patients were included (type I error rate of 5% and a power of 80% when the true response rate is 20%). Here, we report the results on four completed cohorts: patients with a BRCA1, BRCA2, CHEK2 or ATM mutation.

Results

The overall objective response rate across different tumor types was 11% in the BRCA1 (N=27) and 21% in the BRCA2 (N=27) mutated cohorts. Partial responses were seen in pancreatic cancer, gallbladder cancer, endocrine carcinoma of the pancreas and parathyroid cancer. One patient with a BRCA2 germline mutated colon cancer has an ongoing CR with 19+ months on treatment. mPFS in responding patients is 14+ months (5-34+ months). The clinical benefit rate was 63% in the BRCA1 and 46% in the BRCA2 mutated cohorts. No clinical activity was observed in the ATM (N=13) and CHEK2 (N=14) cohorts. Safety data were consistent with the known profile of olaparib.

Conclusions

Olaparib showed efficacy in different cancer types harboring somatic or germline mutations in the BRCA1/2 genes but not in ATM and CHEK2. Patients with any cancer type harboring BRCA1/2 mutations should have access to olaparib with real-world documentation of efficacy in a retrospective register.

Clinical trial identification

NCT03967938.

Editorial acknowledgement

Legal entity responsible for the study

Belgian Society of Medical Oncology (BSMO).

Funding

Kom op tegen Kanker , Fondation contre le Cancer, AstraZeneca and MSD (unrestricted grant, olaparib).

Disclosure

S.R. Joris: Non-Financial Interests, Institutional, Advisory Role: AstraZeneca; Non-Financial Interests, Institutional, Sponsor/Funding: AstraZeneca, MSD. H. Denys: Non-Financial Interests, Institutional, Advisory Role: pfizer, Roche, PharmaMar, AstraZeneca, Eli Lilly, Novartis, Amgen, GSK, Seagen, MSD, Gilead. P.G. Aftimos: Non-Financial Interests, Institutional, Research Grant: Roche; Non-Financial Interests, Institutional, Other, Consulting: Boehringer Ingelheim, Macrogenics, Roche, Novartis, Amcure; Financial Interests, Institutional, Other, Consulting: Servier, G1 therapeutics, Radius, Deloitte; Financial Interests, Institutional, Other, Honoraria: Synthon, Amgen, Novartis; Financial Interests, Institutional, Other, Honoraria: Gilead, Lilly, Daiichi Sankyo. All other authors have declared no conflicts of interest.