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News
A phase 2 trial testing the ATR inhibitor berzosertib combined with carboplatin in heavily pretreated metastatic castration-resistant prostate cancer (mCRPC) was halted early for futility. The combo produced zero responses while generating more serious side effects than the control arm. The trial's early stop highlights the challenge of translating preclinical platinum–ATR synergy into clinical benefit.
A randomized phase 2 trial (NCT03517969) testing the ATR inhibitor berzosertib plus carboplatin in heavily pretreated, biomarker-unselected mCRPC was stopped early after an interim analysis showed the combination was both less effective and more toxic than the control regimen. Enrollment was halted after just 65 of a planned 130 patients were treated.
The combination arm posted a 0% overall response rate compared to 15% in the control arm — all five responses in the control group came from patients receiving docetaxel plus carboplatin (19%), despite prior docetaxel progression. Meanwhile, grade 3+ treatment-related adverse events occurred in 65% of patients on berzosertib vs. 38% on the control, including one fatal sepsis case.
Key Takeaways:
Why it matters: Despite strong preclinical rationale for combining ATR inhibitors with platinum agents, this trial found no clinical benefit — and more harm. The findings suggest that berzosertib dosing constraints and the absence of on-treatment target engagement data may have limited the strategy, pointing to the need for better-validated dosing and biomarker-driven patient selection in future studies.
