Results from a phase 1/2 study of 7MW3711: A novel B7-H3 antibody-drug conjugate (ADC) incorporating a topoisomerase I inhibitor in patients with lung cancer.

3036 Background: 7MW3711 is a B7-H3 targeting ADC comprised of a recombinant humanized monoclonal anti-human B7-H3 antibody conjugated to the topoisomerase I inhibitor via a protease cleavable linker. B7-H3 is upregulated in several malignant cancers, such as lung, ovarian, breast, prostate and esophageal cancer, which plays an important role in multiple processes such as tumor occurrence, development, and immune escape. Here we present the safety and efficacy data of 7MW3711 from a first-in-human phase 1/2 study. Methods: The study enrolled patients (pts) with advanced solid tumor across three segments: dose-escalation (D-esc), dose-expansion (D-exp) and cohort-expansion. In the D-esc and D-exp phase, 7MW3711 was administered intravenously at doses of 1.5, 3.0, 4.5, 5.0, 6.0 mg/kg every three weeks (Q3W). Results: As of the data cutoff on Jan 8, 2025, 37 pts with lung cancer were enrolled and received at least one dose of 7MW3711 (D-esc, n = 25; D-exp, n = 12), which included 16 pts with small cell lung cancer (SCLC) and 21 pts with non-small cell lung cancer (NSCLC). At baseline, the median of prior lines of therapy for all pts was one (range, 1-5). Five pts experienced dose-limiting toxicities (2 pts at 5.0 mg/kg; 3 pts at 6.0 mg/kg), including decreased platelet count, decreased neutrophil count, myelosuppression and decreased appetite. The maximum tolerated dose (MTD) has not yet been determined. The most common Grade ≥3 TRAEs (≥5% of pts) were decreased neutrophil count, decreased white blood cell count, anemia, decreased lymphocyte count, decreased platelet count, hyponatremia, hypokalemia, and myelosuppression. Among 25 pts treated with 7MW3711 at 4.5 mg/kg or above and reaching tumor assessment, 9 partial responses (PRs) were observed. The overall objective response rate (ORR) and disease control rate (DCR) were 36.0% and 96.0%, respectively. 8 pts diagnosed with SCLC were enrolled at 4.5 mg/kg and were evaluable for tumor assessment. All 8 SCLC pts had previously progressed after receiving platinum-based chemotherapy and immune checkpoint inhibitors. The ORR and DCR of them were 62.5% and 100.0%, respectively. Among pts with B7-H3 H-score > 5, the ORR and DCR of lung squamous cell carcinoma (Sq-NSCLC) at 4.5 mg/kg or above were 37.5% (3/8) and 87.5% (7/8), respectively. Conclusions: The data indicated encouraging efficacy of 7MW3711 in SCLC and Sq-NSCLC. The safety profile showed adequate tolerability. The dose optimization and expansion study is continuing to establish the RP2D for 7MW3711. Clinical trial information: NCT06008379 .