EIK1003, a PARP1-selective inhibitor, in combination with paclitaxel (PTX): Initial combination and updated monotherapy results from a phase 1/2 study EIK1003-001 in advanced solid tumors.

Abstract

3102 Background: Non-selective PARP inhibitors (PARPi) demonstrate efficacy in HRR-mutant tumors but cause myelosuppression, potentially mediated by PARP2 inhibition. Overlapping hematologic toxicities have limited PARPi combinations with chemotherapy, restricting their use largely to the maintenance setting. EIK1003 is a potent and selective PARP1 inhibitor that may enable chemotherapy combinations previously not feasible. Here we report the first clinical data for EIK1003 + PTX and updated results for EIK1003 monotherapy. Methods: Cohort 1C evaluated EIK1003 QD (dose level [DL] 1 to 4) + PTX 80 mg/m² QW (Days 1, 8, 15 of 21-day cycles) in patients (pts) with platinum-resistant recurrent ovarian cancer (OC) and HER2(-) breast cancer (BC). Cohort 1A evaluated EIK1003 monotherapy (10 to 160 mg QD). BOIN dose escalation design was used. Primary endpoints were safety and tolerability; secondary endpoints were PK and antitumor activity. Results: As of 21-Nov-2025 safety data cutoff, 51 patients were treated in Cohort 1C; 30 remain on treatment. Median age was 59 years (range 25-81), ECOG PS 0/1 (54.9%/43.1%), and 62% pts received ≥ 4 prior lines of therapy. One DLT of febrile neutropenia was reported at DL4. Gr ≥ 3 TEAEs occurred in 62.7% pts and were mainly hematologic (Table 1). All pts with Gr ≥ 3 anemia had baseline anemia. TEAEs led to dose reduction in 10 pts and discontinuation in 8 pts. No deaths occurred due to TEAEs. The ORR was 23.1% (1 CR, 8 PR), with responses in OC (n=5) and BC (n=4). EIK1003 PK in combination was consistent with monotherapy, with target concentrations achieved at all dose levels. In Cohort 1A, 65 pts were treated. Gr ≥ 3 TEAEs were 43.1%, with anemia and neutropenia being most common (Table 1). 3/6 pts with Gr ≥ 3 anemia had baseline anemia. ORR was 14.3% overall, and 31.3% (5/16) in PARP-naïve pts. Median DOR in confirmed responders was > 6 mos in both cohorts (Table 1). Safety, PK/PD, and preliminary efficacy supported advancement of two doses into Part 2 dose optimization. Conclusions: EIK1003 + PTX demonstrated a tolerable safety profile in a heavily pre-treated population, with hematologic toxicities comparable to historical PTX use (eg, KN-B96, ESMO 2025). These findings represent the first clinical evidence that PARP1-selective inhibitors can be safely combined with chemotherapy. Extended follow-up of EIK1003 monotherapy confirms durable tolerability with antitumor activity. Clinical trial information: NCT06253130 . Safety and efficacy summary. Cohort 1C (EIK1003 + PTX) Cohort 1A (EIK1003 monotherapy) Safety N = 51 N = 65 Gr ≥ 3 TEAEs, % (n) 62.7 (32) 43.1 (28) Neutropenia 43.1 (22) 7.7 (5) Anemia 15.7 (8) 9.2 (6) Efficacy* N = 39 N = 49 ORR per RECIST 1.1, % (n) 23.1 (9) 14.3 (7) DCR (CR+PR+SD), % (n) 74.4 (29) 38.8 (19) DOR, median (range), mos 6.4+ (4.4+, 7.7) 6.2+ (4.2+, 10.4+) * Efficacy evaluable population as of 17-Dec-2025.