BNT326-01: A Phase 1b/2 trial of BNT326/YL202 (HER3 ADC) as monotherapy and in combination with pumitamig (anti-PD-L1 × VEGF bsAb) in patients with advanced solid tumors.

Abstract

TPS3160 Background: BNT326/YL202 is an investigational ADC composed of an anti-HER3 IgG1 monoclonal antibody conjugated to ~8 molecules of a novel topoisomerase I inhibitor payload via a tripeptide linker. HER3 is frequently overexpressed in various solid tumors, particularly in relapsed or refractory tumors, making it an attractive therapeutic target. Increasing evidence suggests that ADCs may enhance the efficacy of immunotherapeutic agents. It is hypothesized that combining BNT326 with immunotherapy including pumitamig, an investigational anti-PD-L1 x VEGF-A bispecific antibody, could lead to better patient outcomes than administering either drug alone. Targeting angiogenesis may facilitate ADC penetration, which in turn could stimulate tumor immunity and increase sensitivity to PD-L1 inhibition. Preclinical in vivo models testing the combination of pumitamig with BNT326 showed superior tumor growth inhibition compared to each treatment alone (Hamilton E, AACR 2025, #648). Methods: This global Phase 1b/2, open-label, adaptive two-part multicohort trial (NCT07070232) will evaluate safety, efficacy, optimal dose and pharmacokinetics of BNT326 in selected indications, both as monotherapy (Part 1) and in combination with pumitamig (Part 2) in patients (≥18y, ECOG PS 0 or 1) with histologically or cytologically confirmed solid tumors that are advanced and/or have relapsed/progressed after prior therapy. Both parts will start enrolling patients independently of each other. In Part 1, patients in Cohorts 1A-C will be randomized to one of two dose levels of BNT326 based on doses derived from the ongoing monotherapy trials (YL202-INT-101-01 [NCT05653752] and YL202-CN-201-01 [NCT06107686], whereas Cohorts 1D, 1E, and 1G receive dose level 2 of BNT326. 1A: cutaneous melanoma 2L+; 1B: NSCLC 2L+, negative for actionable oncogenic alterations; 1C: EGFRm NSCLC 2L+; 1D: rare melanoma; 1E: other advanced solid tumors; 1F: drug-drug interaction cohort, dose defined in randomization cohorts 1A - 1C; and 1G: cervical cancer 2L+. In Part 2, patients in Cohorts 2A and 2B will receive two dose levels of BNT326 in combination with pumitamig. Patients in Cohorts 2D and 2E will receive two dose levels of BNT326 with pumitamig and dose level 2 of BNT326 as monotherapy. Patients in Cohort 2F receive one combination dose level. 2A: cutaneous melanoma 2L+; 2B: HER2-negative breast cancer 2L+/1L; 2C (optional, not open): cutaneous melanoma 1L+; 2D: gastric/gastroesophageal junction cancer 2L+; 2E: colorectal cancer 2L+; and 2F: cervical cancer 2L+. Primary endpoints are safety, overall response rate, and pharmacokinetics for cohort 1F. Enrollment for all cohorts is ongoing globally. Clinical trial information: NCT07070232 .