Bristol Myers Squibb (BMS) and SystImmune have reported striking late-stage clinical results for their investigational cancer drug izalontamab brengitecan (iza-bren).
The dual-target EGFRxHER3 antibody-drug conjugate has showed survival gains across multiple hard-to-treat cancers, as per interim Phase 3 results.
The data showed statistically significant improvements in both overall survival (OS) and progression-free survival (PFS) in two aggressive cancers: triple-negative breast cancer (TNBC) and esophageal squamous cell carcinoma (ESCC).
The companies say the drug has now demonstrated clinical benefit in three separate Phase 3 trials, strengthening its profile as a potentially broad-acting oncology therapy.
In the PANKU-Breast02 study, which enrolled heavily pretreated patients with advanced TNBC, iza-bren outperformed standard chemotherapy across all key endpoints.
Median overall survival reached 15.9 months with iza-bren versus 12.5 months with chemotherapy, while progression-free survival nearly tripled to 8.5 months versus 3.1 months.
Response rates also doubled, with 51.7% of patients responding compared to 20.5% on chemotherapy.
“These results highlight the potential for iza-bren to be a new standard of care,” said Dr. Jiong Wu of Fudan University Shanghai Cancer Center.
In the PANKU-Esophagus01 study, patients with recurrent or metastatic ESCC also saw meaningful survival benefits.
Median overall survival improved to 9.8 months versus 7.2 months, while progression-free survival rose to 4.2 months versus 2.0 months. Objective response rates more than doubled to 35.3% compared to 13.1% with chemotherapy.
Dr. Lin Shen of Peking University Cancer Hospital called the results a potential “new benchmark” for a disease with extremely poor outcomes.
Both trials reported a manageable safety profile, though side effects were significant in heavily pretreated populations.
In the esophageal cancer study, grade ≥3 treatment-related adverse events occurred in 85.1% of patients receiving iza-bren, compared with 60.2% on chemotherapy, largely driven by hematologic toxicities. Treatment-related deaths were low in both arms.
In breast cancer, interstitial lung disease events were rare, occurring in 1.4% of patients treated with iza-bren, with no new safety signals identified.
BMS highlighted that iza-bren has now delivered positive Phase 3 outcomes in three different cancer types, including earlier results in nasopharyngeal carcinoma.
Executives say the drug’s dual mechanism—blocking EGFR and HER3 while delivering a cytotoxic payload—could make it a backbone therapy across multiple solid tumors.
“This is a potentially first-in-class EGFRxHER3 bispecific antibody-drug conjugate,” said Yi Zhu of Biokin. “We are proud to share these results as we continue to evaluate iza-bren to unlock the full potential of this dual mechanism of action.”
BMS Chief Medical Officer Cristian Massacesi said the program is aimed at positioning iza-bren as a “cornerstone treatment” and combining it with other therapies.
A New Drug Application for iza-bren in esophageal cancer has already been accepted in China under priority review, signalling regulatory momentum alongside clinical progress.
With three Phase 3 trials now showing positive results, iza-bren is emerging as one of the more closely watched oncology programs in late-stage development.
