Phase Ib/II Trial Reports 70% Objective Response Rate for Pumitamig and B7-H3 ADC in Advanced Small Cell Lung Cancer

The ongoing global Phase Ib/II study evaluated the PD-L1 x VEGF-A bispecific pumitamig combined with the B7-H3-directed antibody-drug conjugate elfe-D in patients with advanced or metastatic SCLC. Dose escalation showed no dose-limiting toxicities, with grade 3 or higher treatment-related adverse events in 23.3% of 193 treated patients and mostly low-grade gastrointestinal or hematologic events. Among efficacy-evaluable SCLC cases, responses included one complete response and 49 partial responses, with line-specific rates of 92.3% first-line, 77.3% second-line, and 52.4% third-line or later; 70% responses persisted after prior DLL3 therapy.

Small cell lung cancer remains a high-mortality disease with limited durable options beyond platinum chemotherapy and PD-L1 monotherapy, where real-world response rates often fall below 30% in relapsed settings. This combination introduces concurrent VEGF and B7-H3 targeting, potentially addressing angiogenesis and tumor immune evasion simultaneously, a strategy not previously tested in lung cancer. Circulating tumor DNA reduction in 96% of patients and clearance in 39% provide early molecular support, yet the single-arm design and immature NSCLC cohort leave open questions about contribution of each agent versus historical benchmarks.

Further dose expansion and randomized Phase III evaluation against standard second-line topotecan or lurbinectedin will be required to confirm clinical benefit and survival impact. Biomarker analyses and longer follow-up are needed to define optimal patient selection and durability beyond the current data cutoff.