A signal-seeking Phase 2 study of olaparib and durvalumab in advanced solid cancers with homologous recombination repair gene alterations

Journal Publication ResearchOnline@JCU
Thavaneswaran, Subotheni;Kansara, Maya;Lin, Frank;Espinoza, David;Grady, John P.;Lee, Chee Khoon;Ballinger, Mandy L.;Sebastian, Lucille;Corpuz, Theresa;Qiu, Min Ru;Mundra, Piyushkumar;Bailey, Charles G.;Schmitz, Ulf;Simes, John;Joshua, Anthony M.;Thomas, David M.
Abstract

Purpose: To determine the safety and efficacy of PARP plus PD-L1 inhibition (olaparib + durvalumab, O + D) in patients with advanced solid, predominantly rare cancers harbouring homologous recombination repair (HRR) defects. Patients and methods: In total, 48 patients were treated with O + D, 16 with BRCA1/2 alterations (group 1) and 32 with other select HRR alterations (group 2). Overall, 32 (66%) patients had rare or less common cancers. The primary objective of this single-arm Phase II trial was a progression-free survival rate at 6 months (PFS6). Post hoc exploratory analyses were conducted on archival tumour tissue and serial bloods. Results: The PFS6 rate was 35% and 38% with durable objective tumour responses (OTR) in 3(19%) and 3(9%) in groups 1 and 2, respectively. Rare cancers achieving an OTR included cholangiocarcinoma, perivascular epithelioid cell (PEComa), neuroendocrine, gallbladder and endometrial cancer. O + D was safe, with five serious adverse events related to the study drug(s) in 3 (6%) patients. A higher proportion of CD38 high B cells in the blood and higher CD40 expression in tumour was prognostic of survival. Conclusions: O + D demonstrated no new toxicity concerns and yielded a clinically meaningful PFS6 rate and durable OTRs across several cancers with HRR defects, including rare cancers.

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British Journal of Cancer

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129

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1532-1827

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11

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Nature Publishing Group

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DOI

10.1038/s41416-023-02311-0