Trastuzumab Pamirtecan Improves PFS in HER2+ Metastatic Breast Cancer

The results from an interim analysis of the trial shared by an independent data monitoring committee and evaluated by blinded independent central review revealed that the investigational therapy met the trial’s primary PFS end point.

Trastuzumab pamirtecan (BNT323/DB-1303) displayed enhanced progression-free survival (PFS) vs ado-trastuzumab emtansine (T-DM1; Kadcyla) in patients with HER2-positive unresectable or metastatic breast cancer previously treated with trastuzumab (Herceptin) and a taxane-based chemotherapy, according to a news release from the drug’s developer, BioNTech SE.¹

The next-generation antibody-drug conjugate (ADC), trastuzumab pamirtecan, was compared with the approved ADC, trastuzumab emtansine, in a phase 3 trial (NCT06265428). The results from an interim analysis of the trial shared by an independent data monitoring committee (IMDC) and evaluated by blinded independent central review (BICR) revealed that the investigational therapy met the trial’s primary PFS end point.

Based on the trial results, the developers plan to discuss the next steps regarding a submission of a biologics license application for trastuzumab pamirtecan in this patient population with the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA).

“This is a milestone in the fruitful collaboration with our colleagues at DualityBio,” Özlem Türeci, MD, chief medical officer and co-founder at BioNTech, said in the news release.¹ “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.”

The open-label, multicenter phase 3 study enrolled 228 patients with HER2-positive unresectable/metastatic breast cancer in China across 48 sites and randomly assigned them 1:1 to receive intravenous trastuzumab pamirtecan or intravenous trastuzumab emtansine.

The primary end point of the study was PFS per RECIST v1.1 criteria based on BICR. Secondary end points included overall survival, objective response rate, duration of response, and safety.

According to the news release, trastuzumab pamirtecan was built from a proprietary Duality Immune Toxin Antibody Conjugates (DITAC) platform as a third-generation topoisomerase-1 inhibitor-based ADC. Furthermore, preclinical and preliminary clinical data have shown that the investigational therapeutic has displayed the potential to target HER2 receptors on solid tumors regardless of expression level, doing so with manageable safety.

Patients eligible for enrollment on the trial were 18 years and older with pathologically confirmed unresectable or metastatic HER2-positive breast cancer, an ECOG performance status of 0 or 1, at least 1 measurable lesion per RECIST v1.1 criteria, and an expected survival of at least 12 weeks.²

Exclusion criteria included use of any prior anti-HER2 ADC therapies; a history of interstitial lung disease, noninfectious pneumonitis, or radiation pneumonitis requiring steroids; a known hypersensitivity to active or inactive ingredients in any of the study drugs; or multiple malignancies within 3 years, with the exception of resected non-melanoma skin cancer, curatively treated in situ tumors, or contralateral breast cancer. Patients with uncontrolled infection, diabetes, hypertension, or systemic disease limiting study compliance, as well as those with an unrecovered toxicity from prior anticancer therapy, were excluded from trial participation.

“With over 350,000 new cases annually, breast cancer has a high incidence rate in China, making it the second most common malignant tumor among women [who are Chinese],” Hua Mu, MD, global medical officer of DualityBio, stated in the news release.¹ “The positive phase 3 data and trastuzumab pamirtecan meeting the primary end point at the interim analysis indicate the potential of the BNT323/DB-1303 program to become a new treatment option for [patients with] breast cancer. Together with our partner BioNTech, we plan the development of trastuzumab pamirtecan in further tumor types towards BLA application in other regions including the [US] and the [EU] to maximize its potential for patients around the world.”

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 SE. September 5, 2025. Accessed September 5, 2025. https://tinyurl.com/c7c5xtsx
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://tinyurl.com/4ctm6bpr