BL-B01D1-LUNG-101 (NCT05983432) is a global, multi-centre, phase I study to evaluate the safety, tolerability, pharmacokinetics, and initial efficacy of iza-bren in participants with metastatic or unresectable NSCLC and other solid tumours. This study will be conducted in two different dosing schedules (Cohort A and Cohort B) and three parts (dose escalation, dose finding and dose expansion). Cohort A will be dosed on Day 1 and Day 8 of a continuous 21-day treatment cycle. Cohort B will be dosed on Day 1 of a continuous 21-day treatment cycle. The primary endpoint includes safety. Secondary endpoints include Objective Response Rate (ORR) by RECIST 1.1 criteria, Duration of Response (DoR), Disease Control Rate (DCR), Progression-Free Survival (PFS) and Overall Survival (OR) and PK analysis.

NSCLC accounts for approximately 80 percent of all lung cancer cases, which remains the leading cause of cancer-related death worldwide. Among patients with NSCLC, 10 percent to 15 percent in Western populations and up to 50 percent in Asian populations harbour activating EGFR mutations. These tumours, most commonly of non-squamous histology, initially respond to EGFR TKIs such as osimertinib. However, resistance is nearly universal, often occurring after about 18 months, and treatment options beyond TKIs and platinum-based chemotherapy provide limited clinical benefit with significant toxicities, highlighting the critical need for new and effective therapies.

SystImmune, in collaboration with BMS outside of China, is developing iza-bren (BL-B01D1), a bispecific Antibody-Drug Conjugate (ADC) that targets both EGFR and HER3, which are highly expressed in various epithelial cancers and are known to be associated with cancer cell proliferation and survival. Iza-bren's dual mechanism of action blocks EGFR and/or HER3 signals to cancer cells, reducing cancer cell proliferation and survival. In addition, upon antibody mediated internalisation, iza-bren's therapeutic novel Topo1i payload is released causing cytotoxic stress that leads to cancer cell death.