147TiP BNT326-02: A phase Ib/II trial of BNT326/YL202 (HER3 ADC) with pumitamig (PD-L1 × VEGF-A bsAb) in non-small cell lung cancer (NSCLC)
Recommended Citation
Spira A, Bulat IV, Schoenfeld A, Popat S, Zhou C, Erman M, Greystoke A, Gadgeel SM, Rotow J, Joshi R, Neal J, Wermke M, Ochsenreither S, Lee CK, Wenger M, Trueck C, Yang N, Haliduola H, Tibes R, Le X. 147TiP BNT326-02: A phase Ib/II trial of BNT326/YL202 (HER3 ADC) with pumitamig (PD-L1 × VEGF-A bsAb) in non-small cell lung cancer (NSCLC). ESMO Open 2026; 11.
Document Type
Conference Proceeding
Publication Date
4-1-2026
Publication Title
ESMO Open
Keywords
atezolizumab, biological product, bispecific antibody, bms 936559, cabozantinib, DNA topoisomerase inhibitor, enoblituzumab, epidermal growth factor receptor, immunoglobulin G1, monoclonal antibody, pembrolizumab, programmed death 1 ligand 1, pumitamig, tripeptide, vasculotropin A, adoptive immunotherapy, adult, antineoplastic activity, brain metastasis, cancer inhibition, catalyst, cell function, China, clinical practice guideline, clinical trial, clustered regularly interspaced short palindromic repeat, conference abstract, controlled study, cost of travel, England, Europe, expert witness, female, genomic medicine, Germany, human, immunotherapy, intravenous drug administration, lung cancer, male, middle aged, non small cell lung cancer, open study, overall response rate, parttime employment, practice guideline, product vigilance, scorpion, T lymphocyte, tumor microenvironment, United Kingdom, young adult
Abstract
Background: Pumitamig (BNT327) is an investigational anti-PD-L1 x VEGF-A bispecific antibody designed to restore effector T-cell function through PD-L1 binding, while co-localizing VEGF-A neutralization to the tumor microenvironment. BNT326/YL202 is an investigational HER3-targeted ADC consisting of an anti-HER3 IgG1 monoclonal antibody linked to ∼8 molecules of a novel topoisomerase I inhibitor via a tripeptide linker. HER3 surface overexpression is common in lung cancer. Preclinical in vivo models showed superior tumor growth inhibition with this combination versus either treatment alone (Hamilton E, AACR 2025, #648). Based on promising clinical data for HER3-targeted ADCs and pumitamig in lung cancer, the trial will assess the combination's safety and efficacy in molecularly defined lung cancer subgroups. Trial design: This global phase Ib/II, open-label trial (NCT07111520) evaluates safety, optimal combination dose, PK, and preliminary anti-tumor efficacy of BNT326 with pumitamig in previously treated or treatment-naïve advanced/metastatic NSCLC. Patients (≥18 years) must have an ECOG PS ≤1 and non-squamous or squamous NSCLC. Part 1: Dose-escalation using a 3+3 design in 2L+ NSCLC (Actionable Genomic Alteration [AGA]+/-). Three dose levels (DL1, DL2, DL3 [optional]) of BNT326 and a fixed dose of pumitamig will be evaluated. Primary endpoint: safety, including dose-limiting toxicities, to determine RP2D. Part 2a: Cohort A: previously treated, cohort B: treatment-naïve, each with two arms (DL1, DL2). Primary endpoints: safety and overall response rate (ORR). Part 2b: Primary endpoint: ORR. Cohort C: EGFR-mutated (m)/wildtype (WT), any PD-L1 expression, with ≥1 prior therapy. Randomized 1:1:1 to BNT326 (DL1 or DL2) with pumitamig or BNT326 alone (DL2). Stratification: EGFRm/WT, squamous/non-squamous, prior immunotherapy (IO)+chemo/IO/chemo. Cohort D: AGA-negative, treatment-naïve. Stratification: squamous/non-squamous, liver/brain metastasis y/n. D1: PD-L1 ≥50%, randomized 1:1:1 to BNT326 (DL2) with pumitamig, pembrolizumab, or pumitamig alone. D2: PD-L1 <50%, randomized 1:1 to BNT326 (DL2) with pumitamig or pembrolizumab + chemotherapy. Enrollment is ongoing globally. Clinical trial identification: NCT07111520.
Volume
11
