DualityBio-originated, BioNTech-partnered trastuzumab pamirtecan delivered up to 49.3% response rates with manageable safety in HER2-expressing advanced endometrial cancer, supporting ongoing Phase 3 development and planned 2026 BLA filing.
Written By: Chikkula Pavan Kumar, PharmD
Reviewed By: Pharmacally Editorial Team
BioNTech reported positive primary analysis results from a Phase 2 cohort evaluating trastuzumab pamirtecan (BNT323/DB-1303), a HER2-targeted antibody-drug conjugate originally developed by DualityBio and co-developed with BioNTech, in patients with HER2-expressing advanced endometrial cancer whose disease progressed after prior therapy. The cohort is part of an ongoing global Phase 1/2a trial (NCT05150691) across multiple solid tumors.
The ADC showed clinically meaningful activity across HER2 expression levels (IHC1+, IHC2+, IHC3+) with responses observed regardless of prior checkpoint inhibitor exposure. The data were presented in an oral session at the 2026 Society of Gynecologic Oncology Annual Meeting.
Phase 2 cohort meets primary endpoint
The Phase 2 cohort included 145 patients with advanced or metastatic HER2-expressing endometrial cancer previously treated with one or more lines of therapy. The study met its primary endpoint in 73 patients with prior checkpoint inhibitor treatment and centrally confirmed HER2 status, showing a confirmed objective response rate (ORR) of 49.3%.
Among centrally tested patients (n=96), confirmed ORR was 47.9% with median progression-free survival of 8.1 months. In 143 efficacy-evaluable patients assessed by local testing, confirmed ORR was 44.1%, including 33.9% in IHC1+, 40.4% in IHC2+, and 73.1% in IHC3+ tumors. Median duration of response was 10.3 months, and median progression-free survival for all evaluable patients was approximately 8.0 months.
Safety profile
The most common treatment-related adverse events were low-grade nausea, anemia, platelet count decrease, and fatigue. Grade 3 or higher treatment-related adverse events occurred in 46.9% of patients. Interstitial lung disease or pneumonitis of grade 3 or higher was reported in 4.8% of patients, with events generally manageable.
Investigator and company commentary
Bhavana Pothuri, M.D., of NYU Langone Perlmutter Cancer Center, noted that responses were observed across HER2 expression levels, including patients with lower HER2 expression and prior immunotherapy exposure, addressing an unmet need in recurrent endometrial cancer.
Prof. Özlem Türeci, M.D., BioNTech’s Chief Medical Officer, said the results support continued development of trastuzumab pamirtecan as monotherapy and in combination approaches for HER2-driven tumors.
Regulatory and development plans
Trastuzumab pamirtecan received Fast Track and Breakthrough Therapy designations from the U.S. FDA in 2023. A global Phase 3 confirmatory trial (Fern-EC-01) comparing trastuzumab pamirtecan with chemotherapy in previously treated HER2-expressing recurrent endometrial cancer is ongoing.
BioNTech and DualityBio plan to submit a biologics license application in 2026, subject to regulatory feedback. Additional Phase 3 development is also underway in HER2-low metastatic breast cancer.
About trastuzumab pamirtecan
Trastuzumab pamirtecan (BNT323/DB-1303) is a third-generation HER2-targeted antibody-drug conjugate delivering a topoisomerase-1 inhibitor payload. Built using DualityBio’s DITAC platform, the therapy is designed to target HER2-expressing tumors across a range of expression levels with a manageable safety profile.
Reference
BioNTech and DualityBio’s Antibody-Drug Conjugate Trastuzumab Pamirtecan Demonstrated Clinically Meaningful Efficacy in Patients with HER2-Expressing, Recurrent Endometrial Cancer, 11 April 2026, https://investors.biontech.de/news-releases/news-release-details/biontech-and-dualitybios-antibody-drug-conjugate-trastuzumab
A Phase 1/2a Study of DB-1303/BNT323 in Advanced/Metastatic Solid Tumors, ClinicalTrials.gov ID NCT05150691, https://clinicaltrials.gov/study/NCT05150691
About the Writer
Chikkula Pavan Kumar, Pharm.D is a Doctor of Pharmacy with a keen interest in clinical pharmacy, pharmacovigilance, and evidence-based practice. In his words, he is passionate about patient safety and translating complex medical information into clear, research-driven communication.