Abstract CT197: A first-in-human (FIH), phase 1/2, dose-escalation, dose-optimization, and dose-expansion study of PARP1-selective inhibitor EIK1003 as monotherapy and in combination in patients with advanced solid tumors

Abstract BACKGROUND: PARP inhibitors (PARPi) selectively kill tumor cells harboring genetic mutations in critical DNA repair genes (e.g., BRCA1/2). While several approved nonselective PARPi have provided robust antitumor activity, they 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 for this class of therapies by retaining antitumor activity while avoiding PARP2-related toxicities. EIK1003 (IMP1734) is a potent PARP1-selective inhibitor that inhibits tumor growth in nonclinical models and may widen the therapeutic index in tumors where nonselective PARPi have demonstrated efficacy. METHODS: Study EIK1003-001 (IMP1734-101) is a global, multi-center, Phase 1/2 study evaluating the safety and potential antitumor activity of EIK1003 as monotherapy and in combination with abiraterone or paclitaxel in patients with advanced solid tumors (NCT#06253130). The study comprises 3 parts: Part 1 (FIH; Dose Escalation), Part 2 (Dose Optimization), and Part 3 (Dose Expansion at the recommended dose for expansion [RDE]). Part 1 of this study is currently enrolling for the dose escalation of EIK1003 in study participants with advanced/recurrent/metastatic ovarian, breast, prostate, or pancreatic cancer. Eligible participants must be ≥ 18 years of age, have histologically or cytologically confirmed tumors as indicated in each study part, and at least 1 RECIST 1.1-measurable lesion and/or pre-specified serum tumor-specific marker. All participants receiving monotherapy must have a deleterious or suspected deleterious mutation in select homologous recombination repair genes. Combination cohorts are opened when adequate safety has been demonstrated for EIK1003 monotherapy, with specific tumor types and eligibility requirements depending on the combination partner. Primary endpoints include safety and tolerability (evaluation of dose-limiting toxicities and determining the maximum tolerated dose, maximum achievable dose, and RDE). Secondary endpoints include evaluation of the pharmacokinetic parameters of EIK1003 and measures of efficacy, including overall response rate, duration of response, progression-free survival, and overall survival. Exploratory endpoints include analysis of pharmacodynamic biomarkers and serial circulating tumor DNA (ctDNA) measurements. This study opened on 11 Dec 2023. Citation Format: Gerald Falchook, Drew Rasco, Jian Zhang, Yongsheng Li, Jianqing Zhu, Joohyuk Sohn, Christina Teng, Bernard Doger, Chih-Yi Hsieh, Caroline Taromino, Yawei Zhang, Viola J. Chen, Guru Sonpavde. A first-in-human (FIH), phase 1/2, dose-escalation, dose-optimization, and dose-expansion study of PARP1-selective inhibitor EIK1003 as monotherapy and in combination in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT197.