UPDATE: EIK1003 Plus Abiraterone Shows Early Activity in HRR-Mutated Prostate Cancer

New results provide updated safety and efficacy data for EIK1003 (formerly IMP1734), an investigational selective PARP1 inhibitor, in combination with abiraterone and prednisone in patients with metastatic prostate cancer harboring homologous recombination repair (HRR) gene alterations.

Unlike conventional PARP inhibitors, EIK1003 selectively targets PARP1 while largely sparing PARP2, potentially reducing the hematological toxicity associated with broader PARP inhibition.

The ongoing phase 1/2 EIK1003-001 trial evaluated the combination in 34 patients, including 29 with metastatic castration-resistant prostate cancer (mCRPC) and five with metastatic castration-sensitive disease (mCSPC). More than half had received at least three previous treatment lines. Eligible genetic alterations included BRCA1/2, ATM, ATR, CDK12, CHEK2, and other HRR genes.

Among 15 patients evaluable for radiological response, four (26.7%) achieved partial responses, including three with mCRPC and one with mCSPC. Disease control was observed in 93.3%. However, PSA reductions exceeding 50% occurred in only 3 of 20 evaluable patients (15%), all of whom also achieved radiological responses.

The safety analysis showed grade 3 or higher anemia in four patients (11.8%), all of whom already had mild or moderate anemia before treatment. No dose-limiting toxicities or treatment-related deaths were reported. Adverse events led to dose interruptions in 38.2% of patients, reductions in 2.9%, and treatment discontinuation in 8.8%.

These findings provide preliminary evidence that selective PARP1 inhibition can be combined with androgen receptor-directed therapy at pharmacologically active doses. However, the study is small, non-randomized, and includes patients with different disease states and genetic alterations. No gene-specific efficacy results were reported, and the apparent hematological tolerability advantage over non-selective PARP inhibitors has not been established through direct comparison.

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