Safety and efficacy of EIK1003, a selective PARP1 inhibitor, as monotherapy in participants with advanced solid tumors.

3122 Background: PARP inhibitors (PARPi) selectively kill tumor cells with genetic mutations in critical DNA repair genes (eg, BRCA1/2). While approved nonselective PARPi may provide antitumor activity, they are associated with hematologic toxicities. Drugs inhibiting PARP1 but not PARP2 may improve the risk-benefit profile by retaining antitumor activity while avoiding PARP2-related toxicities. EIK1003 (IMP1734) is a potent PARP1-selective inhibitor that may widen the therapeutic index in susceptible tumors. Methods: EIK1003-001 (IMP1734-101) is an ongoing global, multi-center, Phase 1/2 study evaluating the safety and efficacy of EIK1003 (once daily oral) as monotherapy or in combination with anticancer agents in participants (pts) with advanced solid tumors (NCT#06253130). Pts must be ≥ 18 yrs with deleterious or suspected deleterious mutations in select homologous recombination repair genes. This abstract reports the interim safety and efficacy from Part 1 monotherapy (dose escalation). Results: At the data cut (10 Jan 2025), 32 pts were treated in the first 4 completed dose levels (DLs; n = 3 to 15 per DL, including backfill) of monotherapy dose escalation. There were no dose-limiting toxicities and a maximum tolerated dose has not been reached. The majority (29/32) of pts were female. Pts had a median age of 60 years (31 to 76), and cancers represented included ovarian (n = 15), HER2-negative breast (n = 10), pancreatic (n = 3), fallopian tube (n = 2), and prostate cancer (n = 1). Pts received a median of 3 (range 1 to 11) prior lines of therapy for metastatic disease with 50% receiving prior PARPi. To date, EIK1003 demonstrated a tolerable safety profile. All pts experienced at least one treatment-emergent adverse event (TEAE), and 13/32 experienced at least one ≥ Grade 3 TEAE. 27/32 pts experienced a treatment-related AE (TRAE), 6 of which experienced a ≥ Grade 3 TRAE. Hematologic toxicities (Grade 3) included neutropenia (3/32) and anemia (1/32). 7/32 experienced a serious adverse event (including one related case of Grade 3 vomiting). There were no Grade 4 AEs or deaths due to AE, and no trends in AEs by DL were observed. EIK1003 PK was linear, with a half-life > 24 hours. Of the 13 ovarian cancer patients with post-treatment scan assessments, 3 experienced partial response (PR; one each at DL2, DL3, and DL4) and 3 experienced stable disease (SD; one at DL1 and two at DL3) by RECIST v1.1. For these 3 PRs, all had a CA125 response. Of the 6 breast cancer patients with post-treatment scan assessments, there was 1 PR (DL3) and 1 SD (DL1) via RECIST v1.1. Conclusions: To date, EIK1001 has demonstrated tolerable safety and encouraging preliminary efficacy. Dose escalation is ongoing. Updated safety and efficacy data will be reported at the time of presentation. Clinical trial information: 06253130 .