Ceralasertib Monotherapy in Patients with ATM-Altered Advanced Solid Tumors or Metastatic Castration-Resistant Prostate Cancer: Data from the Phase 2a PLANETTE Study

PURPOSE: 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 AND METHODS: 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. 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, 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. CONCLUSIONS: Ceralasertib monotherapy was tolerated; however, responses were limited. Alternative patient selection and combination treatments are being explored.