SystImmune and Bristol Myers Squibb have announced positive results from prespecified interim analyses of two phase 3 studies evaluating izalontamab brengitecan (iza-bren), an investigational and potentially first-in-class EGFRxHER3 bispecific antibody-drug conjugate (ADC).
The studies demonstrated iza-bren achieved statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) in heavily pretreated, unresectable locally advanced or metastatic triple-negative breast cancer and recurrent or metastatic oesophageal squamous cell carcinoma. These data, presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, support iza-bren’s potential as a new standard of care in these challenging cancer types.
Iza-bren has now shown clinical benefit in three phase 3 trials, underscoring its broad therapeutic potential. PANKU-breast02 is the first phase 3 study of a bispecific ADC to report positive results for dual primary endpoints of both PFS and OS in TNBC, while PANKU-Esophagus01 marks the first phase 3 trial of a bispecific ADC in oesophageal cancer to report positive dual primary endpoints of both PFS and OS. Iza-bren previously demonstrated positive phase 3 results in recurrent or metastatic nasopharyngeal carcinoma (NPC), presented at ESMO 2025.
Results
The phase 3 PANKU-Breast02 trial evaluated iza-bren in patients with unresectable locally advanced or metastatic TNBC whose disease progressed following one-two prior lines of systemic therapy for advanced disease, including prior taxane therapy. Patients were randomised 1:1 to receive iza-bren (n=207) or physician’s choice of chemotherapy (TPC; n=211), which included eribulin, capecitabine, gemcitabine, or vinorelbine. The study met both dual primary endpoints at a prespecified interim analysis, demonstrating a statistically significant and clinically meaningful improvement in OS and BICR-assessed PFS with iza-bren compared to TPC.
- With a median follow-up of 11 months, median OS was 15.9 months with iza-bren vs. 12.5 months with TPC (HR: 0.60; 95% CI: 0.42-0.85; p=0.0019)
- Median PFS by Blinded Independent Central Review (BICR) was 8.5 months with iza-bren vs. 3.1 months with TPC (HR: 0.29; 95% CI: 0.22-0.38; p<0.0001)
- The confirmed objective response rate (ORR) assessed by BICR was 51.7% with iza-bren compared to 20.5% with TPC (odds ratio, 4.3; 95% CI: 2.8-6.7)
Iza-bren showed a manageable safety profile in this heavily pre-treated patient population, with no new safety signals observed. Grade >3 treatment-emergent adverse events (TEAEs) were predominantly hematologic toxicities and consistent with the known safety profile of iza-bren.
Any grade interstitial lung disease (ILD) was reported in three (1.4%; one case of grade one and two cases of grade two) patients treated with iza-bren and 0 patients treated with TPC. Treatment discontinuation due to TEAEs occurred in four (1.9%) patients treated with iza-bren and one (0.5%) patients treated with TPC.
The phase 3 PANKU-Esophagus01 trial evaluated iza-bren in patients with recurrent or metastatic oesophageal squamous cell carcinoma who had progressed after first-line treatment with a PD-1/PD-L1 inhibitor plus platinum-based chemotherapy (n=249) compared to chemotherapy of physician’s choice (n=248). Results from the interim analysis show iza-bren demonstrated a statistically significant and clinically meaningful improvement in the dual primary endpoints of OS and BICR-assessed PFS.
- Median OS was 9.8 months with iza-bren vs. 7.2 months with chemotherapy (HR: 0.64; 95% CI: 0.49-0.83; p=0.0004).
- Median PFS by BICR was 4.2 months with iza-bren vs. 2.0 months with chemotherapy (HR:0.50; 95% CI: 0.40-0.63; p<0.0001).
- Iza-bren also demonstrated an improvement in responses with an ORR by BICR of 35.3% compared to 13.1% with chemotherapy.
A New Drug Application for iza-bren for the treatment of recurrent or metastatic oesophageal squamous cell carcinoma has been accepted by the Center for Drug Evaluation (CDE) under China’s National Medical Products Administration (NMPA) and included in the priority review process.
