Efficacy and safety of MHB088C, a novel B7-H3-targeted ADC, in patients with relapsed extensive-stage small cell lung cancer (ES-SCLC): Subgroup analysis from a phase 1/2 multicenter study.

Abstract

8510 Background: MHB088C is a novel B7-H3-targeted antibody-drug conjugate (ADC) containing the potent SuperTopoi payload that is 5 to 10 times more potent than Dxd. Initial findings from an ongoing phase 1/2 study indicated that MHB088C was generally well tolerated, with early signs of clinical activity (ASCO 2024, abstract #3012). This analysis presents efficacy and safety results for the subset of pts with ES-SCLC. Methods: This study consisted of 2 parts: dose-escalation (part 1) and expansion (part 2). Part 1 evaluated the safety and tolerability of MHB088C at doses ranging from 0.8 to 4.0 mg/kg, administered intravenously every 2 (Q2W) or 3 weeks (Q3W). Doses of 1.6 mg/kg Q2W, 2.0 mg/kg Q2W, and 2.4 mg/kg Q3W were selected for part 2. Part 2 focused on assessing safety and prospective efficacy of MHB088C in selected tumor types, including SCLC. Results: At data cutoff (January 3, 2025), a total of 91 pts with relapsed ES-SCLC had received ≥ 1 dose of MHB088C (1.6 mg/kg Q2W, n=28; 2.0 mg/kg Q2W, n=33; 2.4 mg/kg Q3W, n=30). MHB088C showed encouraging efficacy in relapsed ES-SCLC (Table). The objective response rates were 42.9%, 57.6%, and 46.7% in the 1.6, 2.0, and 2.4 mg/kg cohorts, respectively, with median progression-free survival (PFS) of 5.5, 5.9, 5.5 months. Safety data were consistent with previous reports. The most common grade≥3 treatment-related adverse events were neutropenia, platelet count decreased and anemia. The 1.6 and 2.0 mg/kg cohorts exhibited favorable safety profiles, with only single-digit rates of the aforementioned hematologic adverse events. One case (1.0%) of mild interstitial lung disease (ILD) was reported. Conclusions: MHB088C demonstrated promising anti-tumor activity and favorable safety in previously treated pts with ES-SCLC. A Phase 3 study is planned to compare the efficacy and safety of MHB088C with standard-of-care chemotherapy in relapsed ES-SCLC. Clinical trial information: CTR20231298 . 1.6 mg/kg Q2W(n=28) 2.0 mg/kg Q2W(n=33) 2.4 mg/kg Q3W(n=30) Unconfirmed ORR, (%) 42.9 57.6 46.7 Confirmed ORR, (%) 21.4 42.4 43.3 DCR, n (%) 89.3 87.9 93.3 Median PFS, month 5.5 5.9 5.5