BioNTech reports modest Phase 3 breast-cancer benefit and lung toxicity
The 541-patient DYNASTY-Breast02 trial met its primary endpoint, but the partners say potential patient benefit is limited.
Adrian Kessler
Modest efficacy and lung toxicity have clouded a Phase 3 breast-cancer endpoint win, as BioNTech SE NASDAQBNTX and DualityBiologics (Suzhou) Co., Ltd. HKG9606 reported potentially limited benefit on Monday. Their 541-patient DYNASTY-Breast02 study tested trastuzumab pamirtecan against chemotherapy.
The Oct. 26 announcement said the drug significantly improved progression-free survival in hormone receptor-positive, HER2-low metastatic breast cancer after endocrine therapy. The companies described the improvement as modest, reported severe and fatal lung-disease events, and said they would discuss the data before determining next steps.
BioNTech is a large German vaccine maker building a global cancer-drug business through partnered and internally developed treatments.
BioNTech's Nasdaq-listed shares NASDAQBNTX closed at US$88.12 at 4:00 p.m. EDT on Oct. 23, before the readout. Monday's release gave no regulatory filing timetable and no account of FDA feedback on the trial design.
The Endpoint Win Leaves Key Numbers Undisclosed
DYNASTY-Breast02 randomly assigned patients equally to trastuzumab pamirtecan or a single chemotherapy chosen by the investigator. The chemotherapy options were capecitabine, paclitaxel or nab-paclitaxel, and patients had not received chemotherapy for metastatic disease.
The global, open-label study enrolled patients whose disease had progressed after prior hormone treatment. Eligibility included progression after at least two hormone-treatment lines, or within six months of first-line hormone therapy combined with a CDK4/6 inhibitor.
The release supplied no median progression-free survival for either arm, hazard ratio, confidence interval or p value. Investors therefore cannot quantify the benefit beyond the companies' description of statistical significance and modest improvement. Overall survival, a key secondary endpoint, remained immature at this interim analysis.
Interstitial lung disease occurred more frequently than in earlier trastuzumab pamirtecan trials, with most cases graded 1 or 2. The companies reported a small proportion of severe and fatal events but disclosed neither the number affected nor the number of deaths.
The release said the remaining safety profile was consistent with earlier trials. Without event rates by arm, the announcement does not allow a numerical comparison of lung toxicity against chemotherapy.
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"The available efficacy and safety data, as of this data cut-off date, suggest that the potential benefit to patients would be limited in the context of the HR+/HER2-low metastatic breast cancer treatment landscape," the companies said in the release.
Enhertu Sets An Approved Benchmark
An approved treatment already reaches this setting. AstraZeneca PLC LONAZN NYSEAZN announced on Jan. 27, 2025 that the FDA approved Enhertu for HR-positive, HER2-low or HER2-ultralow metastatic breast cancer progressing after endocrine therapy.
Its DESTINY-Breast06 study reported median progression-free survival of 13.2 months with Enhertu against 8.1 months with chemotherapy in the overall population. That population included HER2-ultralow disease, so the figures cannot establish a direct comparison with trastuzumab pamirtecan.
Trastuzumab pamirtecan is an investigational HER2-targeting antibody-drug conjugate. The partners also listed an ongoing late-stage endometrial-cancer study and an earlier-stage solid-tumour study; Monday's announcement did not report results from either.
BioNTech reported €16.6 billion in cash, cash equivalents and security investments at June 30 in its Aug. 4 financial update. That historical balance is not a program-specific cash-runway estimate, and Monday's release provided none.
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The next scheduled investor update is BioNTech's third-quarter results on Nov. 3, with a corporate webcast at 8:00 a.m. EST. It provides the next dated opportunity to clarify development priorities; the partners have set no date for a decision on this breast-cancer program.
