1316 Initial monotherapy clinical activity of invikafusp alfa, a first-in-class TCR β-chain-targeted bifunctional antibody, in tissue-agnostic, TMB-H patients from STARt-001, a phase 1/2 trial

作者：Aurélien Marabelle, Elena Garralda, Ryan J. Sullivan, Antoîne Italiano, Claire F. Friedman, Manuel Pedregal, Kai He, Marijo Bilušić, Carlos Gomez-Roca, Nicholas Tschernia, Alberto Hernando Calvo, Matthieu Roulleaux Dugage, Mercedes Herrera, Guru P. Sonpavde, Meredith P Pelster, Diane Tseng, Wasif M. Saif, Ann W. Silk, Shannon McCue, Karunya Srinivasan, Zhen Su, Ke Liu, Lillian L. Siu, James L. Gulley · 年份：2025 · DOI：10.1136/jitc-2025-sitc2025.1316 · 被引用次数：2 · 研究领域：Monoclonal and Polyclonal Antibodies Research、Biosimilars and Bioanalytical Methods、HER2/EGFR in Cancer Research

Background Invikafusp alfa (STAR0602), a selective, dual T cell agonist targeting Vβ6/10 TCRs, is being evaluated as monotherapy in the Phase 2 expansion of START-001, a multicenter Phase 1/2 trial in patients with tissue-agnostic TMB-H (≥ 10 mut/Mb) and/or microsatellite instability (MSI)-H solid tumors.Methods Ongoing Phase 2 expansion enrolls patients with TMB-H/MSI-H solid tumors to 3 separate cohorts: tissue-agnostic TMB-H or MSI-H, and colorectal cancer. All patients receive recommended Phase 2 dose of 0.08 mg/kg i.v. invikafusp, Q2W. Here we report the first pooled results ever presented for tissue-agnostic, TMB-H patients from Phase 2 and Phase 1 who received optimal biological dose (range 0.08 to 0.12 mg/kg).Results As of 30 June 2025, 47 patients across 17 different TMB-H solid tumors were enrolled: 33% received ≥ 4 lines of prior therapy; 70% received prior immune checkpoint blockade (ICB) and 30% were ICB-naïve because ICB were either not standard of care or not approved for the condition.Of 47 patients, 33 had ≥ 1 post treatment tumor assessment. Overall, invikafusp showed tissue-agnostic, anti-tumor activity (partial response [PR] and tumor regression) in 10 different TMB-H tumor types (table 1). Specifically, 16 patients (49%) had target lesion reduction with 8 (24%) PR and 19 (58%) stable disease (82% disease control) per RECIST. PR and tumor regression were seen in both ICB-resistant (primary and secondary) and ICB-naive patients, suggesting invikafusp’s tiss...