Trastuzumab Pamirtecan Hits Phase 3 PFS End Point in HER2+ Metastatic Breast Cancer

Treatment with the next-generation, HER2-directed antibody-drug conjugate (ADC) trastuzumab pamirtecan (BNT323/DB-1303) led to an improvement in progression-free survival (PFS) compared with trastuzumab emtansine (T-DM1; Kadcyla) in patients with HER2-positive, unresectable or metastatic breast cancer who previously received trastuzumab (Herceptin) and a taxane-based chemotherapy, meeting the primary end point of a phase 3 trial (NCT06265428) conducted in China.1

“This is a milestone in the fruitful collaboration with our colleagues at DualityBio,” Özlem Türeci, MD, chief medical officer and co-founder at BioNTech, stated in a news release. “We believe that trastuzumab pamirtecan is an ADC candidate with enormous potential which makes it an important asset in our global oncology strategy including combinational approaches. It is the first of our late-stage oncology programs to meet its primary end point in a pivotal phase 3 trial and also highlights our commitment to bringing novel oncology treatments with distinct profiles to patients.”

Following the positive data readout at a prespecified interim analysis, BioNTech, the drug developer, intends to discuss next steps for the submission of a biologics license application (BLA) with the Center for Drug Evaluation of China’s National Medical Products Administration.

What Was the Design of the Phase 3 Trial Examining Trastuzumab Pamirtecan?

The multicenter, open-label, randomized study evaluated trastuzumab pamirtecan—a third-generation, HER2-targeted ADC with a topoisomerase-1 inhibitor payload—vs T-DM1 in patients at least 18 years of age with pathologically confirmed unresectable or metastatic, HER2-positive breast cancer who previously received treatment with trastuzumab and a taxane.1,2

Key inclusion criteria comprised an ECOG performance status of 0 or 1, at least 1 measurable lesion per RECIST 1.1 criteria, and a life expectancy of at least 12 weeks.2 Patients were excluded if they received prior treatment with a HER2-directed ADC, had a history of pneumonitis or interstitial lung disease requiring steroids, and uncontrolled infection requiring intervention.

The study enrolled approximately 224 patients who were randomly assigned 1:1 to receive trastuzumab pamirtecan or T-DM1.

Beyond the primary end point of blinded independent central review–assessed PFS per RECIST 1.1 criteria, secondary end points included overall survival, investigator-assessed PFS, objective response rate, duration of response, pharmacokinetics, safety, and patient-reported outcomes.

What Prior Designations Were Granted to Trastuzumab Pamirtecan?

In December 2023, the FDA granted breakthrough therapy designation to trastuzumab pamirtecan for the treatment of patients with advanced endometrial cancer who progressed on or after treatment with immune checkpoint inhibitors.3 The regulatory agency also granted fast track designation to the ADC for the treatment of patients with endometrial cancer in January 2023.

What Are the Next Steps for the ADC?

The agent is also being investigated vs investigator’s choice of chemotherapy in patients with hormone receptor-positive, HER2-low metastatic breast cancer whose disease progressed on hormone- and/or CDK4/6 inhibitor–based therapy as part of the phase 3 trial DYNASTY-Breast02 trial (NCT06018337).4

References

1. BioNTech and DualityBio announce phase 3 trial of ADC candidate BNT323/DB-1303 met primary endpoint of progression free survival in HER2-positive metastatic or unresectable breast cancer. News release. BioNTech. September 5, 2025. Accessed September 5, 2025. https://investors.biontech.de/news-releases/news-release-details/biontech-and-dualitybio-announce-phase-3-trial-adc-candidate
2. A study to compare DB-1303/​BNT323 versus T-DM1 in breast cancer. ClinicalTrials.gov. Updated December 12, 2024. Accessed September 5, 2025. https://clinicaltrials.gov/study/NCT06265428
3. BioNTech and DualityBio receive FDA breakthrough therapy designation for antibody-drug conjugate candidate BNT323/DB-1303 in endometrial cancer. News release. BioNTech. December 21, 2023. Accessed September 5, 2025. https://investors.biontech.de/news-releases/news-release-details/biontech-and-dualitybio-receive-fda-breakthrough-therapy
4. A study of DB-1303/​BNT323 vs investigator's choice chemotherapy in HER2-low, hormone receptor positive metastatic breast cancer (DYNASTY-Breast02). ClinicalTrials.gov. Updated July 18, 2025. Accessed September 5, 2025. https://clinicaltrials.gov/study/NCT06018337