BioNTech has reported modest efficacy and unexpected safety findings in a phase 3 breast cancer trial, leading the company to conclude its HER2-directed candidate may offer “limited” benefits in the current treatment landscape.
The study, DYNASTY-Breast02, enrolled patients with HR-positive, HER2-low metastatic breast cancer. AstraZeneca and Daiichi Sankyo defined the HER2-low category with their antibody-drug conjugate (ADC) Enhertu. BioNTech’s trastuzumab pamirtecan (t-pam) uses the same anti-HER2 antibody as Enhertu but is differentiated by its linker technology and cytotoxic payload.
DYNASTY-Breast02 raises doubts about whether those differences improve clinical outcomes. Working with its partner DualityBiologics, BioNTech reported a statistically significant but modest improvement in progression-free survival (PFS) in the phase 3 trial.
A statistically significant PFS benefit versus chemotherapy “was largely expected,” BMO Capital Markets analysts said in a note to investors. With BioNTech’s press release lacking data on the magnitude of the PFS improvement, the analysts interpreted the efficacy readout as “an incremental negative.”
BioNTech reported the modest PFS improvement alongside a higher rate of interstitial lung disease (ILD) than it saw in earlier trials of the ADC. Most ILD cases were grade 1 or 2. A “small proportion of patients” had severe or fatal events, the company acknowledged. The biopharma declined to provide more details of the data or their potential implications for the company’s other ADCs.
“Given increasing physician sensitivity to pulmonary toxicity for HER2-directed ADCs, these findings are likely to weigh on competitive positioning,” the analysts said. “Taken together, DYNASTY-Breast02 data lowers our confidence in the overall competitive positioning of t-pam in HR+/HER2-low mBC.”
BioNTech echoed the doubts, stating the results suggest t-pam’s potential benefit to patients would be limited in the context of the current treatment landscape. BMO analysts interpreted the line as a sign that t-pam is less likely to be developed in the indication. BioNTech and DualityBio will discuss the data and decide the next steps. Overall survival data were immature as of the interim analysis.
BMO analysts picked up on signs of growing uncertainty about the ADC’s future on BioNTech’s earnings call in August. Noting that BioNTech executives saw the ADC’s path forward as less certain in an evolving treatment landscape, the analysts said they “view potential downside associated with discontinuation as more limited given relatively smaller patient opportunities.”
BioNTech already has data from a registrational cohort of endometrial carcinoma (EC) patients. In a note to investors last week, TD Cowen analysts said a filing for approval in EC “technically remains on track for 2026.” However, the analysts suspected that BioNTech wouldn't file for approval in EC alone, given the small market size, and would instead wait to include breast cancer data in the filing package.
The DYNASTY-Breast02 readout comes two weeks after BioNTech's mRNA cancer vaccine BNT113 missed one of its dual primary endpoints in a phase 2/3 clinical trial. The back-to-back setbacks leave the company looking to readouts on its anti-CTLA-4 antibody gotistobart for a near-term boost to its pipeline. In the longer term, the PD-L1xVEGF-A bispecific pumitamig is central to BioNTech’s prospects.
The drug developer presented data on pumitamig, including in combination with its B7-H3-directed ADC, at the European Society for Medical Oncology conference over the weekend. The initial ADC combination results showed encouraging early activity, with “deep tumor shrinkage and responses that deepened beyond initial disease stabilization,” BioNTech said in its ESMO presentation. The results added to a growing body of evidence supporting the potential use of pumitamig with ADCs, the company added.