Phase 2 Data Position Trastuzumab Pamirtecan as a Promising Option in Endometrial Cancer

BioNTech and DualityBio reported encouraging Phase 2 results for trastuzumab pamirtecan, an investigational HER2-targeted antibody-drug conjugate, in pretreated, HER2-expressing recurrent endometrial cancer.  Presented at the 2026 SGO Annual Meeting on Women’s Cancers in San Juan, the findings suggest trastuzumab pamirtecan (BNT323/DB-1303) could offer a new option in recurrent endometrial cancer, especially for patients with lower HER2 expression or prior checkpoint inhibitor treatment.

The data come from cohort 2b of the ongoing global Phase 1/2a study, NCT05150691, which enrolled 145 patients with advanced or metastatic HER2-expressing endometrial cancer after first or later lines of therapy. According to BioNTech, this is the largest study so far to report results for a HER2-directed ADC in this disease.

Primary Endpoint Met With Strong Response Rates

The trial met its primary efficacy endpoint. In the prespecified group of 73 patients who had received prior checkpoint inhibitor therapy and whose HER2 status was centrally confirmed, the confirmed objective response rate was 49.3% (95% CI, 37.4 to 61.3). Across all centrally tested patients, numbering 96, the confirmed objective response rate was 47.9% (95% CI, 37.6 to 58.4), with a median progression-free survival of 8.1 months (95% CI, 5.5 to 11.8).

Among 143 efficacy-evaluable patients assessed by local HER2 testing, the confirmed objective response rate was 44.1% (95% CI, 35.8 to 52.6). Activity was seen across the HER2 expression spectrum: 33.9% in IHC1+, 40.4% in IHC2+, and 73.1% in IHC3+ disease. The median duration of response was 10.3 months, and median progression-free survival for all evaluable patients was 8.0 months (95% CI, 5.6 to 8.3), regardless of prior checkpoint inhibitor exposure.

Results Highlight Activity in a Real-World Patient Population

“Endometrial cancer is one of the few cancers with an increasing mortality rate, and there is an urgent need for new treatment options, especially for patients with recurrent disease with lower HER2 expression levels,” said Dr. Bhavana Pothuri, Medical Director of the Clinical Trials Office and Director of Gynecologic Oncology Research at the NYU Langone Perlmutter Cancer Center. “We are encouraged by these results for trastuzumab pamirtecan, which showed clinically meaningful responses across all HER2 levels. Importantly, these results were seen in a broad patient population that reflects real-world clinical practice.”

Safety Profile Remains Consistent With HER2-Targeted ADCs

Safety appeared consistent with the known profile of HER2-targeted ADCs. The most common treatment-related adverse events were low-grade nausea, anemia, platelet count decrease, and low-grade fatigue. Grade 3 or higher treatment-related adverse events occurred in 46.9% of patients. Grade 3 or higher adjudicated interstitial lung disease or pneumonitis was reported in 4.8%. BioNTech said most severe events were manageable with appropriate medical care.

Positive Data Support Further Clinical Development

“These positive results in patients with endometrial cancer including those with lower HER2 expression levels support the potential of trastuzumab pamirtecan,” said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. “HER2 remains an important therapeutic target, particularly in gynecologic cancers and breast cancer. We are continuing to advance trastuzumab pamirtecan, both as a monotherapy and in novel-novel treatment combination approaches, with the aim to address the significant unmet medical needs in the treatment of patients with HER2-driven tumors.”

Trastuzumab pamirtecan, also known as BNT323/DB-1303, is a third-generation topoisomerase 1 inhibitor-based ADC. The drug received both Fast Track and Breakthrough Therapy designations from the FDA for endometrial cancer in 2023. A confirmatory Phase 3 trial, Fern-EC-01, is ongoing, and BioNTech and DualityBio plan to file a biologics license application in 2026, pending FDA feedback.