• Trastuzumab pamirtecan, an investigational HER2-targeted antibody-drug conjugate, met the primary efficacy endpoint in a Phase 2 cohort of heavily pre-treated patients with HER2-expressing, recurrent endometrial cancer, an area of high unmet medical need
• Data demonstrated clinically meaningful antitumor activity across all HER2 expression levels and a manageable safety profile, with centrallyⁱ HER2-tested patients showing a confirmed objective response rate of 47.9% in all evaluable patients, 49.3% in patients with prior immune checkpoint inhibitor treatment, and a median progression-free survival of 8.1 months
• Largest trial to date to report results for a HER2-targeted antibody-drug conjugate in this indication supports potential of trastuzumab pamirtecan in real-world patient populations, including patients with lower HER2 expression levels and prior checkpoint inhibitor treatment
  
  

BioNTech SE  announced positive results from the primary analysis of a Phase 2 cohort evaluating trastuzumab pamirtecan (BNT323/DB-1303) in patients with HER2-expressing, advanced endometrial cancer whose disease progressed on or after first-line chemotherapy with or without prior checkpoint inhibitor treatment. This cohort is part of a global Phase 1/2a clinical trial (NCT05150691) investigating the HER2-targeted antibody-drug conjugate (“ADC”) candidate trastuzumab pamirtecan in multiple solid tumors.

The data demonstrated clinically meaningful efficacy and a manageable safety profile for trastuzumab pamirtecan monotherapy across all HER2 immunohistochemistry (“IHC”) expression levels (IHC1+, IHC2+, IHC3+)ⁱⁱ. Outcomes were consistent among patients regardless of prior checkpoint inhibitor treatment. The data will be presented today in an oral session at the 2026 Society of Gynecologic Oncology (“SGO”) Annual Meeting on Women’s Cancers in San Juan, Puerto Rico.

“Endometrial cancer is one of the few cancers with an increasing mortality rate,¹ and there is an urgent need for new treatment options, especially for patients with recurrent disease with lower HER2 expression levels where current standard-of-care chemotherapy offers only a 15 % response rate²,” said Bhavana Pothuri, M.D., Medical Director of the Clinical Trials Office (CTO) 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, including patients who have received prior immune checkpoint inhibitor treatment and those with visceral metastases.”

The analysis of the Phase 2 cohort included 145 patients with advanced or metastatic HER2-expressing endometrial cancer whose disease had progressed following first- or later lines of therapy. This cohort met its primary efficacy endpoint of objective response rate (“ORR”) evaluated in 73 patients previously treated with checkpoint inhibitor therapy and confirmed HER2 status by central testing, showing a confirmed ORR of 49.3% (95% CI: 37.4, 61.3). In all centrally tested patients (n=96) the confirmed ORR was 47.9% (95% CI: 37.6, 58.4) with a median progression-free survival (“mPFS”) of 8.1 months (95% CI: 5.5, 11.8).

Among the 143 efficacy-evaluable patients by localⁱ HER2 status testing, the confirmed ORR was 44.1% (95% CI: 35.8, 52.6). Trastuzumab pamirtecan consistently demonstrated encouraging antitumor activity across all HER2 expression levels, with comparable results whether HER2 testing was conducted locally or centrally. Among patients with local HER2 testing, the confirmed ORR was 33.9% (IHC1+) and 40.4% (IHC2+) in patients with lower levels of HER2 expression, and 73.1% (IHC3+) in patients with higher HER2 expression levels. The median duration of response (“mDoR”) was 10.3 months. mPFS for all evaluable patients (n=145), whether they had received prior checkpoint inhibitor treatment or not, was 8.0 months (95% CI: 5.6, 8.3).

The safety profile was manageable and as expected for HER2-targeted ADCs. The most common treatment-related adverse events (TRAEs) were low-grade nausea, anemia, platelet count decrease, and low-grade fatigue. Grade ≥3 treatment-related adverse events (TRAEs) were reported in 68 of 145 (46.9%) patients. Adjudicated cases of interstitial lung disease (“ILD”) or pneumonitis of grade ≥3 occurred in 4.8% of patients and were consistent with the known safety profile of HER2-targeted ADC therapies. The majority of events grade 3 or higher were efficiently manageable with appropriate medical interventions.

“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 received Fast Track and Breakthrough Therapy designations from the U.S. Food and Drug Administration (“FDA”) for the treatment of endometrial cancer in 2023. A global confirmatory Phase 3 clinical trial Fern-EC-01 (NCT06340568) evaluating trastuzumab pamirtecan monotherapy compared to chemotherapy in previously treated patients with HER2-expressing, recurrent endometrial cancer is ongoing. BioNTech and DualityBio plan to file a biologics license application (“BLA”) in 2026, subject to regulatory feedback from the FDA.