Abstract CT306: Phase 1 first-in-human multicenter open-label study of ZW191, a folate receptor α (FRα)-targeting antibody-drug conjugate (ADC), in patients with advanced solid tumors: Part 1 dose-escalation results

Abstract Background: ZWI-ZW191-101 (NCT06555744) is an ongoing, 2-part study; Part 1 being dose-escalation and Part 2 dose optimization and expansion. Here, we summarize results from Part 1 dose-escalation of the study (data cut: 1 Dec 2025). Methods: Eligible patients aged ≥18 years with recurrent platinum-resistant ovarian cancer (PROC), endometrial cancer (EC), or non-small cell lung cancer (NSCLC) who had progressed on available systemic treatment options, were recruited, independent of FRα expression. Intravenous ZW191 was administered every 3 weeks (Q3W). Part 1 endpoints included safety, tolerability, and antitumor activity per RECIST v1.1. Results: A total of 51 patients (49 female; median age: 60 years [range, 35-79]; 35 with OC; 11 with EC; 5 with NSCLC) received ZW191 Q3W (1.6 mg/kg to 11.2 mg/kg). Patients had received a median of 3 (1-9) prior lines of treatment. 34 (67%) patients remained on the study treatment at time of data cut. All 51 patients were safety evaluable (Table). The most common Grade ≥3 treatment-related adverse events were neutropenia (18%), anemia (10%), and thrombocytopenia (6%). Among 48 response-evaluable patients (≥1 post-baseline scan), the unconfirmed objective response rate (ORR) was 52% (Table). Responses were observed in tumors with FRα low/negative, intermediate, and high expression. Across doses 6.4-9.6 mg/kg, patients with OC and EC had an unconfirmed ORR of 61% and 57%, respectively. Median time to response was 6 weeks. Additional data, including confirmed ORR, duration of response, and progression-free survival, will be presented. Conclusion: ZW191 demonstrated compelling efficacy regardless of FRα expression in a heavily pretreated population of patients with OC and EC, and a favorable safety profile. Dose levels of 6.4 and 9.6 mg/kg Q3W are being evaluated in the Part 2a dose optimization phase of the study. Citation Format: Patricia LoRusso, David Sommerhalder, Kosei Hasegawa, Kenichi Harano, David S. Tan, Noboru Yamamoto, David M. O’Malley, Kathleen N. Moore, Sarah E. Church, Lin Lu, Sabeen Mekan, Pranshul Chauha, Jung-Yun Lee. Phase 1 first-in-human multicenter open-label study of ZW191, a folate receptor α (FRα)-targeting antibody-drug conjugate (ADC), in patients with advanced solid tumors: Part 1 dose-escalation results [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 CT306.