Ceralasertib is an oral ataxia telangiectasia and Rad3-related (ATR) inhibitor with preclinical activity in ataxia-telangiectasia mutated (ATM)-altered cancers. The phase 2a PLANETTE study evaluated ceralasertib in previously treated advanced solid tumors (Cohort A) or metastatic castration-resistant prostate cancer (Cohort B) with ATM alterations (ATM mutations and/or ATM protein deficiency).
Patients received ceralasertib 160 mg BID on days 1-14 of a 28-day cycle. Efficacy was evaluated in patients with centrally confirmed ATM alterations. The primary endpoint was objective response rate (ORR; Cohort A) or composite response rate (CRR: radiographic response, PSA response, or circulating tumor cell conversion; Cohort B). Secondary endpoints included progression-free survival (PFS) and safety.
Cohorts A and B included 30 and 15 patients, respectively. ORR (Cohort A) was 7.1% (80% confidence interval [CI]: 1.9-17.9; n=2/28): one complete response ongoing at 14.1 months (breast cancer) and one partial response ongoing at 7.4 months (endometrial cancer). CRR (Cohort B) was 7.7% (80% CI: 0.8-28.6; n=1/13). In patients with centrally confirmed ATM protein loss, ORR was 18.2% (80% CI: 4.9-41.5; n=2/11) and CRR was 0% (80% CI: 0-28.0; n=0/7). Median PFS was 3.7 months in each cohort (Cohort A, 80% CI: 1.9-5.6; Cohort B, 80% CI: 1.9-not calculable). Grade ≥3 AEs occurred in 50.0% of Cohort A and 53.3% of Cohort B patients. The most common AEs overall were asthenia/fatigue, nausea, and anemia.
Ceralasertib monotherapy was tolerated; however, responses were limited. Alternative patient selection and combination treatments are being explored.
Cancer research communications. 2026 May 29 [Epub ahead of print]
Rahul R Aggarwal, Antoine Italiano, Susan M Domchek, Oscar Goodman, Sophie Postel-Vinay, Jesus García-Donás, Tanya Dorff, Zachery R Reichert, Armelle Vinceneux, Neal Shore, Catherine H Marshall, Joshua Armenia, Graeme Parr, Aleksandra Kmieciak, Natalia Lukashchuk, Olga Murina, Daniel Slade, Neel Shah, Bienvenu Loembé, Emma Dean, Elhan Sanai, Wassim Abida
University of California, San Francisco San Francisco, CA United States., Institut Bergonié Bordeaux France., University of Pennsylvania Philadelphia, PA United States., Nevada Oncology Specialists Las Vegas, NV United States., Institut Gustave Roussy Villejuif France., Instituto de Investigacion Sanitaria HM Hospitales Madrid Spain., City Of Hope National Medical Center Duarte, CA United States., University of Michigan-Ann Arbor Ann Arbor, MI United States., Centre Léon Bérard Lyon France., Carolina Urologic Research Center Myrtle Beach, SC United States., Johns Hopkins Medicine Baltimore, MD United States., AstraZeneca (United Kingdom) Cambridge United Kingdom., Memorial Sloan Kettering Cancer Center New York, NY United States.