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 advanced solid tumors.

3035 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, 6.0 mg/kg every three weeks (Q3W); 4.0 mg/kg every two weeks (Q2W). Results: As of the data cutoff on Jan 2, 2025, 43 pts were enrolled and received at least one dose of 7MW3711 (D-esc, n = 15; D-exp, n = 28). At baseline, the median of prior lines of therapy for all pts was 2 (range, 1-9). No dose-limiting toxicities (DLTs) were observed in the D-esc phase. The maximum tolerated dose (MTD) has not yet been reached. The most common Grade ≥3 TRAEs (≥5% of pts) were decreased white blood cell count, anemia, decreased neutrophil count, decreased lymphocyte count, decreased platelet count, diarrhea, and hypokalemia. Among 33 pts treated with 7MW3711 at 4.0 mg/kg or above and reaching tumor assessment, 8 partial responses (PRs) were observed. The objective response rate (ORR) and disease control rate (DCR) were 24.2% and 84.8%, respectively. 15 pts diagnosed with esophageal cancer (EC), ovarian cancer (OC) and prostate cancer (PC) were enrolled at 4.5 mg/kg or above and were evaluable for tumor assessment. All EC pts had previously progressed after receiving platinum-based chemotherapy and immune checkpoint inhibitors. All OC pts were platinum-resistant. All PC pts had previously progressed after receiving docetaxel and endocrine therapy. The ORR of EC, OC and PC was 33.3%, 60.0% and 50.0%, respectively. The DCR of EC, OC and PC was 100.0%. Objective responses were also observed in pts with other solid tumor types, such as lung adenocarcinoma and breast cancer. Conclusions: The data indicated encouraging efficacy of 7MW3711 in advanced EC, OC and PC. The safety profile showed adequate tolerability. The dose optimization and expansion study is continuing to establish the RP2D for 7MW3711. Clinical trial information: NCT06008366 .