Cancer research communications · 2026
Ceralasertib Monotherapy in Patients with ATM-Altered Advanced Solid Tumors or Metastatic Castration-Resistant Prostate Cancer: Data from the Phase IIa PLANETTE Study.
СтатьяКлиническое исследование II фазыМногоцентровое исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Aggarwal Rahul, Italiano Antoine, Domchek Susan M, Goodman Oscar, Postel-Vinay Sophie, Garcia-Donas Jesus, Dorff Tanya, Reichert Zachery R, Vinceneux Armelle, Shore Neal, Marshall Catherine H, Armenia Joshua, Parr Graeme, Kmieciak Aleksandra, Lukashchuk Natalia, Murina Olga, Slade Daniel, Shah Neel, Loembé Bienvenu, Dean Emma, Sanai Elhan, Abida Wassim
Аннотация
PURPOSE: Ceralasertib is an oral ataxia telangiectasia and Rad3-related (ATR) inhibitor with preclinical activity in ataxia-telangiectasia mutated (ATM)-altered cancers. The phase IIa 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 AND METHODS: Patients received ceralasertib 160 mg twice daily on days 1 to 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, prostate-specific antigen response, or circulating tumor cell conversion; cohort B). Secondary endpoints included progression-free survival (PFS) and safety.
RESULTS: 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, the ORR was 18.2% (80% CI, 4.9-41.5; n = 2/11) and CRR was 0% (80% CI, 0-28; n = 0/7). The 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 adverse events (AE) occurred in 50% of cohort A and 53.3% of cohort B patients. The most common AEs overall were asthenia/fatigue, nausea, and anemia.
CONCLUSIONS: Ceralasertib monotherapy was tolerated; however, responses were limited. Alternative patient selection and combination treatments are being explored.
SIGNIFICANCE: In the phase IIa PLANETTE study in advanced/metastatic ATM-altered cancers, ceralasertib 160 mg twice daily (days 1-14, 28-day cycle) was tolerated; objective responses were limited, corroborating previous findings with ATR inhibitors in ATM-deficient tumors. Optimizing biomarker-based patient selection beyond ATM deficiency represents a key aspect of future ATR inhibitor development.
PATIENTS AND METHODS: Patients received ceralasertib 160 mg twice daily on days 1 to 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, prostate-specific antigen response, or circulating tumor cell conversion; cohort B). Secondary endpoints included progression-free survival (PFS) and safety.
RESULTS: 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, the ORR was 18.2% (80% CI, 4.9-41.5; n = 2/11) and CRR was 0% (80% CI, 0-28; n = 0/7). The 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 adverse events (AE) occurred in 50% of cohort A and 53.3% of cohort B patients. The most common AEs overall were asthenia/fatigue, nausea, and anemia.
CONCLUSIONS: Ceralasertib monotherapy was tolerated; however, responses were limited. Alternative patient selection and combination treatments are being explored.
SIGNIFICANCE: In the phase IIa PLANETTE study in advanced/metastatic ATM-altered cancers, ceralasertib 160 mg twice daily (days 1-14, 28-day cycle) was tolerated; objective responses were limited, corroborating previous findings with ATR inhibitors in ATM-deficient tumors. Optimizing biomarker-based patient selection beyond ATM deficiency represents a key aspect of future ATR inhibitor development.