On October 17, 2025 SystImmune Inc. (SystImmune), a clinical-stage biotechnology company, and Bristol Myers Squibb (NYSE: BMY) reported the oral presentation of the first disclosure of the safety and efficacy data from the global phase I US-Lung-101 study (NCT05983432) of iza-bren (BL-B01D1), a potentially first-in-class EGFR x HER3 bispecific antibody-drug conjugate (ADC), at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 in Berlin, Germany. Iza-bren is jointly developed by SystImmune and Bristol Myers Squibb under a collaboration and exclusive license agreement in territories outside of Mainland China. In August 2025, iza-bren was granted breakthrough therapy designation by U.S. FDA for patients with previously treated EGFR-mutated NSCLC based on the data from China studies and this global study.

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This study evaluated the safety and efficacy of iza-bren in global patients with heavily pre-treated metastatic or unresectable advanced non-small cell lung cancer (NSCLC) and other solid tumors. At the data cut-off (DCO) of July 23, 2025, iza-bren has demonstrated:

Promising antitumor activity in heavily pre-treated patients across multiple tumor types, including EGFR mutant and wildtype NSCLC
Manageable safety profile, with hematologic adverse events effectively managed by standard medical measures, and no interstitial lung disease was observed
In the study, 107 patients with advanced solid tumors were treated, including non-small cell lung cancer (NSCLC) patients with and without EGFR mutations. Most had received several prior therapies. The most common side effects were blood-related, such as neutropenia. These were generally manageable and rarely led to dose reductions or serious complications. No new safety concerns were identified, and no cases of interstitial lung disease were seen. Mandatory preventive measures for neutropenia have been added in ongoing global studies.

For patients receiving 2.5 mg/kg (Days 1 and 8 every 3 weeks), 55% (11 of 20) showed a confirmed response, with a median progression-free survival of 5.4 months. Confirmed responses were also seen in both the subgroup with EGFR-mutated NSCLC (3 of 10 patients) and those without the mutation (3 of 4 patients).

Global registrational studies of first line metastatic TNBC (IZABRIGHT-Breast01, NCT06926868), second line metastatic EGFRmt NSCLC (IZABRIGHT-Lung01, NCT05983432) and second line metastatic Urothelial Cancer (IZABRIGHT-Bladder01, NCT07106762) are ongoing, with studies in other indications planned.

"The first global presentation of iza-bren builds on the compelling data initially observed in Chinese patients, showing consistent efficacy in a heavily pre-treated global population," said Jonathan Cheng, M.D., Chief Medical Officer, SystImmune. "These results support iza-bren’s potential as a bispecific ADC treatment option across multiple tumor types, and we are excited to continue advancing this important program through our global collaboration with Bristol Myers Squibb."

"We are committed to developing first-in-class and best-in-class medicines that can meaningfully improve outcomes for patients with difficult-to-treat cancers," said Anne Kerber, Senior Vice President, Head of Development, Hematology, Oncology and Cell Therapy, Bristol Myers Squibb. "The encouraging activity observed with iza-bren in this early global study reinforce our confidence in its potential, and we look forward to the ongoing registrational studies across lung, breast, and urothelial cancers."

About the BL-B01D1-LUNG-101 Phase I clinical trial
BL-B01D1-LUNG-101 (NCT05983432) is a global, multi-center, 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 tumors. 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.

About EGFRmt NSCLC
Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancer cases, which remains the leading cause of cancer-related death worldwide. Among patients with NSCLC, 10% to 15% in Western populations and up to 50% in Asian populations harbor activating EGFR mutations. These tumors, 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, effective therapies.

About iza-bren
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 internalization, iza-bren’s therapeutic novel Topo1i payload is released causing cytotoxic stress that leads to cancer cell death.

(Press release, Bristol-Myers Squibb, OCT 17, 2025, View Source;and-Bristol-Myers-Squibb-Announce-First-Global-Phase-I-Results-of-Iza-bren-an-EGFR-x-HER3-Bispecific-Antibody-Drug-Conjugate-in-Patients-with-Advanced-Solid-Tumors-at-ESMO-2025/default.aspx [SID1234656729])