BioNTech Trial Enrolls 541 Patients, Shows Modest Improvement in Breast Cancer
Key Facts
BioNTech and DualityBio said on October 26, 2026, that the global Phase 3 DYNASTY-Breast02 trial met its primary endpoint, with a statistically significant but modest improvement in progression-free survival compared with investigator’s choice of chemotherapy. The trial included 541 patients, randomly assigned in a 1:1 ratio to trastuzumab pamirtecan or single-agent chemotherapy. The study targeted patients with metastatic hormone receptor-positive, HER2-low breast cancer whose disease had progressed during hormonal therapy and who had not received chemotherapy for their metastatic disease. Progression-free survival was the primary measure, while overall survival was a key secondary measure. The companies said overall survival data were immature at the interim analysis. The announcement did not provide the magnitude of the progression-free survival improvement or detailed efficacy figures.
The control arm’s treatment was selected from capecitabine, paclitaxel or nab-paclitaxel, at the investigator’s discretion, putting the investigational drug up against single-agent chemotherapy options. Participants were divided equally between the two arms, according to BioNTech’s announcement, but the company did not publish arm-specific results or the size of the difference between them. Eligibility required disease progression after at least two prior lines of hormonal therapy, or progression within six months of starting first-line hormonal therapy with a CDK4/6 inhibitor in the metastatic setting. This requirement limits the finding to a group that had previously received hormonal therapy and experienced disease progression, with differences in participants’ prior treatment paths. Choosing progression-free survival as the primary measure defines the endpoint on which the trial’s success announcement was based. The statement did not report a mature result for overall survival, the key secondary measure.
The efficacy signal came with a safety concern: the companies said the rate of interstitial lung disease was higher than rates recorded in previous trials of the drug. Most cases, according to the statement, were Grade 1 or 2, while severe or fatal cases were reported in a small proportion of patients, in Grades 3 to 5. The announcement gave no rates or case counts, so it did not provide quantitative detail to compare the size of this signal across trials. BioNTech and DualityBio said the available efficacy and safety data suggest the potential benefit for patients may be limited among current treatment options for metastatic hormone receptor-positive, HER2-low breast cancer. The treatment context includes Enhertu, whose approval the U.S. Food and Drug Administration expanded in January 2025 for adults with unresectable or metastatic HR-positive and HER2-low or HER2-ultralow breast cancer after disease progression on one or more hormonal therapies in the metastatic setting. This places the investigational drug in a treatment area where an approved therapy is already available for the stated group.
The result is part of a broader development program for trastuzumab pamirtecan; BioNTech said the drug is being studied in three ongoing clinical trials, including two global Phase 3 trials and one global Phase 1/2 trial. The companies said on September 5, 2025, that a separate Phase 3 trial in China in unresectable or metastatic HER2-positive breast cancer met its primary endpoint of progression-free survival at a prespecified interim analysis. That study concerns a different group from the participants in DYNASTY-Breast02 and does not represent the result of the current trial. In an August 2026 update, BioNTech said the primary analysis of DYNASTY-Breast02 was expected in the fourth quarter of 2026, based on event accrual projections. The companies also said in the same update that they intended to determine the optimal regulatory path based on the totality of clinical data in endometrial and breast cancer. After announcing the current results, they said they would discuss the data and determine next steps.