Abstract CT287: A first-in-human (FIH), Phase 1/2, dose-escalation and dose-optimization study of central nervous system (CNS)-penetrant, PARP1-selective inhibitor EIK1004 in patients with advanced solid tumors with or without brain metastases

Abstract Background: PARP inhibitors (PARPi) selectively kill tumor cells harboring genetic mutations in critical DNA repair genes (e.g., BRCA1/2). Approved nonselective PARPi have demonstrated robust antitumor activity, but are associated with significant hematologic toxicities that limit dose intensity and clinical benefit. Drugs that selectively inhibit PARP1, but spare PARP2, may improve the risk-benefit profile by retaining antitumor activity while avoiding PARP2-related toxicities. Furthermore, current PARPi have variable brain penetrance, limiting their utility for targeting CNS tumors or brain metastases. EIK1004 (IMP1707) is a potent, CNS-penetrant, PARP1-selective inhibitor that demonstrates tumor growth inhibition in preclinical brain metastasis models. Methods: Study EIK1004-001 (IMP1707-101) is a FIH, global, multi-center, Phase 1/2 study evaluating the safety and potential antitumor activity of EIK1004 monotherapy in patients with advanced ovarian, breast, prostate, or pancreatic cancer, with or without brain metastases (NCT06907043). The study consists of Part 1 (Dose Escalation; using the Bayesian optimal interval [BOIN] design) and Part 2 (Dose Optimization). All participants must have a deleterious or suspected deleterious mutation in select homologous recombination repair genes and received no more than one prior line of PARPi treatment. Eligible participants must be ≥ 18 years, have histologically or cytologically confirmed tumors and received appropriate prior antitumor therapies, and have evaluable disease (eg, at least 1 measurable lesion by RECIST 1.1 [or RANO-BM for brain metastases] and/or serum tumor markers). Primary endpoints include safety and tolerability including identifying the maximum tolerated dose or maximum achievable dose, and recommended dose(s) for expansion (RDE). Secondary endpoints include evaluation of EIK1004 pharmacokinetics and preliminary antitumor activity including overall response, duration of response, and progression-free survival. Part 2 will open once the RDE is determined from Part 1. This study opened on 23-Jan-2025 and is actively enrolling participants. Citation Format: Timothy A. Yap, Jian Zhang, Yanhua Xu, Sanum Chaudry, Kevin H. Eng, Yawei Zhang, Viola J. Chen, Gerald Falchook. A first-in-human (FIH), Phase 1/2, dose-escalation and dose-optimization study of central nervous system (CNS)-penetrant, PARP1-selective inhibitor EIK1004 in patients with advanced solid tumors with or without brain metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT287.