SystImmune, Inc. and Bristol Myers Squibb (BMS) said Sichuan Biokin Pharmaceutical Co., Ltd., SystImmune’s parent company, has reported positive prespecified interim results from two Phase 3 studies of izalontamab brengitecan (iza‑bren), an investigational and potentially first‑in‑class EGFRxHER3 bispecific antibody‑drug conjugate. The trials showed statistically significant and clinically meaningful improvements in overall survival (OS) and progression‑free survival (PFS) in heavily pretreated patients with unresectable locally advanced or metastatic triple‑negative breast cancer (TNBC) in the PANKU‑Breast02/BL‑B01D1‑307 study and in recurrent or metastatic esophageal squamous cell carcinoma (ESCC) in the PANKU‑Esophagus01/BL‑B01D1‑305 study. These data were presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.
Iza‑bren has now shown clinical benefit in three Phase 3 trials. PANKU‑Breast02 is described as the first Phase 3 study of a bispecific ADC in TNBC to report positive dual primary endpoints of both PFS and OS, while PANKU‑Esophagus01 is the first Phase 3 trial of a bispecific ADC in esophageal cancer to report positive dual primary endpoints of PFS and OS. Iza‑bren previously demonstrated positive Phase 3 results in recurrent or metastatic nasopharyngeal carcinoma, presented at ESMO 2025.
In PANKU‑Breast02, patients with unresectable locally advanced or metastatic TNBC whose disease had progressed after one to two prior lines of systemic therapy for advanced disease, including taxane therapy, were randomized 1:1 to iza‑bren (n=207) or physician’s choice of chemotherapy (TPC; n=211: eribulin, capecitabine, gemcitabine, or vinorelbine). At a median follow‑up of 11 months, median OS was 15.9 months with iza‑bren versus 12.5 months with TPC (hazard ratio [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 versus 3.1 months with TPC (HR 0.29; 95% CI 0.22–0.38; p<0.0001). The confirmed objective response rate by BICR was 51.7% with iza‑bren compared with 20.5% with TPC (odds ratio 4.3; 95% CI 2.8–6.7).
In this TNBC population, iza‑bren showed a manageable safety profile with no new safety signals. Grade >3 treatment‑emergent adverse events were mainly hematologic and consistent with the known safety profile of iza‑bren. Interstitial lung disease of any grade was reported in 3 patients (1.4%; one grade 1, two grade 2) on iza‑bren and in no patients on TPC. Treatment discontinuation due to adverse events occurred in 4 patients (1.9%) in the iza‑bren arm and 1 patient (0.5%) in the TPC arm.
PANKU‑Esophagus01 evaluated iza‑bren in patients with recurrent or metastatic ESCC who had progressed after first‑line treatment with a PD‑1/PD‑L1 inhibitor plus platinum‑based chemotherapy, comparing iza‑bren (n=249) with physician’s choice of chemotherapy (n=248). Interim results showed median OS of 9.8 months with iza‑bren versus 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 versus 2.0 months with chemotherapy (HR 0.50; 95% CI 0.40–0.63; p<0.0001). The objective response rate by BICR was 35.3% with iza‑bren compared with 13.1% with chemotherapy.
In ESCC, iza‑bren also showed a manageable safety profile. Grade >3 treatment‑related adverse events, predominantly hematologic, occurred in 85.1% of patients receiving iza‑bren and 60.2% of those on chemotherapy. Treatment‑related adverse events leading to discontinuation occurred in 2% of patients on iza‑bren and 3.3% on chemotherapy. Treatment‑related deaths were reported in 1.2% of iza‑bren‑treated patients and 1.6% of chemotherapy‑treated patients. Rates of all‑grade and grade >3 interstitial lung disease were low in both arms (iza‑bren: 1.6%/0.8%; chemotherapy: 0.4%/0.4%).
Yi Zhu, M.D., chief executive officer of Biokin, said iza‑bren has shown significant clinical benefit in three Phase 3 studies across different cancers and that the ASCO data further support its value over current standards of care. Cristian Massacesi, M.D., executive vice president, chief medical officer and head of development at Bristol Myers Squibb, said iza‑bren may address a gap for patients who develop resistance or disease progression after prior therapies and could have potential in earlier‑line settings; he noted a broad development program and the possibility that iza‑bren could become a cornerstone treatment in several cancers and be readily combined with other therapies.
A New Drug Application for iza‑bren in recurrent or metastatic ESCC has been accepted by China’s Center for Drug Evaluation under the National Medical Products Administration and granted priority review. PANKU‑Breast02 and PANKU‑Esophagus01 are sponsored by Biokin in mainland China, while outside China, iza‑bren is being jointly developed by SystImmune and Bristol Myers Squibb under a collaboration and exclusive license agreement.
Subscribe to our e-Newsletters
Stay up to date with the latest news, articles, and events. Plus, get special offers
from American Pharmaceutical Review – all delivered right to your inbox!
Sign up now!