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., and Thomas, David M. (2023) A signal-seeking Phase 2 study of olaparib and durvalumab in advanced solid cancers with homologous recombination repair gene alterations. British Journal of Cancer. (In Press)

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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.

Item ID:	79182
Item Type:	Article (Research - C1)
ISSN:	1532-1827
Copyright Information:	Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Date Deposited:	05 Jul 2023 02:31
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3211 Oncology and carcinogenesis > 321104 Cancer therapy (excl. chemotherapy and radiation therapy) @ 80% 31 BIOLOGICAL SCIENCES > 3102 Bioinformatics and computational biology > 310208 Translational and applied bioinformatics @ 20%
SEO Codes:	20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 100%
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