Safety and Efficacy of Ceralasertib plus Olaparib for Advanced/Metastatic Triple-Negative Breast Cancer in Three Molecular Strata: The Phase II VIOLETTE Study.

Authors

Andrew Tutt, Zbigniew Nowecki, Renata Szoszkiewicz, Seock-Ah Im, Hendrik-Tobias Arkenau, Anne Armstrong, William Jacot, Jee Hyun Kim, Marc Webster, Judith Balmaña, Suzette Delaloge, Ronny Odegbami, Ed Casson, Bienvenu Loembé, Natalia Lukashchuk, Moritz Drachsler, Emma Dean, Kevin Punie

Published in

Clinical cancer research : an official journal of the American Association for Cancer Research. Sep 21, 2026. Epub Sep 21, 2026.

Abstract

VIOLETTE (NCT03330847) assessed olaparib alone or with ceralasertib (ATR inhibitor) or adavosertib (WEE1 inhibitor) as second-/third-line treatment in three molecular strata of patients with previously treated, PARP inhibitor-naïve, advanced triple-negative breast cancer (TNBC).
Patients were randomized 1:1:1 to olaparib 300 mg twice daily (BD), ceralasertib 160 mg once daily (Days 1-7; 28-day cycles) + olaparib 300 mg BD, or adavosertib 150 mg BD (Days 1-3, 8-10; 21-day cycles) + olaparib 200 mg BD. Patients were stratified by presence of tumoral homologous recombination repair (HRR) pathway mutations (m): BRCA1/2m, non-BRCA1/2m HRRm, or non-HRRm. Primary endpoint was progression-free survival (PFS) by blinded independent central review.
273 patients were randomized: 114, 112, and 47 to the olaparib, ceralasertib + olaparib, and adavosertib + olaparib arms, respectively. The adavosertib + olaparib arm was terminated early due to unacceptable toxicity. Median PFS of ceralasertib + olaparib was 7.4, 3.9, and 3.6 months in the BRCA1/2m, non-BRCA1/2m HRRm, and non-HRRm strata, respectively, and did not differ significantly from olaparib (HR 1.02 [90% CI, 0.63-1.66], 0.54 [90% CI, 0.28-1.03], and 0.76 [90% CI, 0.50-1.14], respectively). In the non-HRRm group objective response rates (ORR) were significantly improved for ceralasertib + olaparib (15.4%) vs. olaparib (3.9%; OR, 4.45; 90% CI, 1.30‒21.20; P = 0.0425). No unexpected safety signals were reported for ceralasertib or olaparib.
In patients with advanced PARP inhibitor-naïve non-HRRm TNBC, ceralasertib + olaparib significantly improved ORR versus olaparib. However, clinical significance is limited without improvement in PFS.

PMID:
42765908
Bibliographic data and abstract were imported from PubMed on 21 Sep 2026.

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