MAINZ, Germany, AND SHANGHAI, China
October 26, 2026 — BioNTech SE (Nasdaq: BNTX) and DualityBio (HKEX: 9606.HK) announced topline results from the global Phase 3 DYNASTY-Breast02 trial, evaluating trastuzumab pamirtecan (BNT323/DB-1303) in patients with hormone receptor-positive (HR+)/HER2-low metastatic breast cancer whose disease had progressed following endocrine therapy. The study met its primary endpoint, demonstrating a statistically significant but moderate improvement in progression-free survival (PFS) compared with investigator-selected chemotherapy. The companies said the results must be considered alongside the safety findings and currently available treatment options for this patient population. Data from the interim analysis of overall survival (OS), a key secondary endpoint, were immature at the time of analysis. The safety assessment identified a higher incidence of interstitial lung disease (ILD) than had been observed in earlier studies of trastuzumab pamirtecan. Most cases were Grade 1 or 2, but a small proportion were serious or fatal, including Grade 3–5 events. The companies reported that the overall safety profile was consistent with previous clinical trials and that no new safety signals were identified. However, they indicated that the potential benefit for patients could be limited relative to existing treatment options. BioNTech and DualityBio will jointly review the available efficacy and safety data and determine the next steps for the program. The announcement does not provide the numerical PFS results, hazard ratio, confidence interval or p-value, limiting assessment of the magnitude of benefit from the topline findings alone. The companies are continuing to evaluate trastuzumab pamirtecan in other clinical settings, including HER2-expressing recurrent uterine cancer and advanced or metastatic solid tumors.
DYNASTY-Breast02 Evaluates Treatment After Endocrine Therapy
DYNASTY-Breast02 is a global, randomized, multicenter, open-label Phase 3 trial designed to assess trastuzumab pamirtecan against investigator-selected chemotherapy in patients with HR+/HER2-low metastatic breast cancer. The study randomized 541 patients in a 1:1 ratio to receive either the investigational antibody-drug conjugate (ADC) or chemotherapy monotherapy. Eligible tumors had low HER2 expression, defined as immunohistochemistry (IHC) 1+ or IHC 2+ with negative in situ hybridization (ISH−). Patients had disease progression after at least two prior lines of endocrine therapy, or progression within six months of starting first-line endocrine therapy combined with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor in the metastatic setting. The chemotherapy options were capecitabine, paclitaxel or nab-paclitaxel, selected by the treating investigator. PFS was the primary endpoint, while OS was an important secondary endpoint. The trial’s topline results showed a statistically significant improvement in PFS for trastuzumab pamirtecan compared with chemotherapy. However, the companies characterized the improvement as moderate and stated that the potential clinical benefit appeared limited in the context of available treatment options. Because numerical efficacy estimates were not included in the announcement, the absolute difference in median PFS and the relative reduction in the risk of disease progression or death cannot be quantified from the reported information. The OS analysis was also immature, meaning the available follow-up was insufficient to establish a definitive survival outcome. These limitations are important when interpreting the trial’s primary endpoint and considering the overall clinical relevance of the results. The safety findings, particularly the observed ILD cases, are an additional consideration in determining the development strategy. The companies said they would review the full data together before deciding how to proceed with the candidate in this indication.
Interstitial Lung Disease Emerges as a Key Safety Consideration
The DYNASTY-Breast02 safety results identified a higher rate of ILD than had been observed in previous clinical studies of trastuzumab pamirtecan. Most cases were Grade 1 or 2, while a small proportion involved serious and fatal events classified as Grade 3–5. ILD is an important safety concern in the evaluation of cancer therapies because inflammation or damage affecting lung tissue can lead to respiratory complications. The announcement did not provide the exact incidence of ILD, the number of fatal cases or detailed comparisons between treatment groups. Accordingly, the scale of the risk and its relationship to the overall benefit-risk profile cannot be independently quantified from the topline release. BioNTech and DualityBio stated that the broader safety profile was consistent with previous clinical trials and that no new safety signals were identified. Nevertheless, the higher ILD rate represents a notable finding for the ongoing clinical and development assessment. Trastuzumab pamirtecan is a third-generation HER2-targeted antibody-drug conjugate designed to deliver a topoisomerase I inhibitor to tumor cells expressing HER2. The candidate is based on DualityBio’s proprietary Duality Immune Toxin Antibody Conjugates (DITAC) platform. ADCs combine an antibody that recognizes a target associated with cancer cells with a linked cytotoxic payload intended to deliver treatment to those cells. HER2 expression levels can vary among tumors, and the DYNASTY-Breast02 trial specifically studied patients whose cancers were classified as HER2-low. The companies will need to consider both the magnitude of PFS improvement and the safety findings when deciding whether and how to continue development in this population. The current announcement does not establish an overall survival benefit or a favorable benefit-risk profile sufficient to support a regulatory approval claim.
Advertisement
BioNTech and DualityBio Review the Broader Development Program
Beyond DYNASTY-Breast02, BioNTech and DualityBio are evaluating trastuzumab pamirtecan in two additional clinical programs. The candidate is being studied in Fern-EC-01, a randomized global Phase 3 trial comparing trastuzumab pamirtecan with investigator-selected chemotherapy in previously treated patients with HER2-expressing recurrent uterine cancer. The study is registered as NCT06340568. The companies are also conducting an ongoing Phase 1/2 study, NCT05150691, evaluating the candidate in patients with advanced or metastatic solid tumors. Together, these studies are intended to assess the investigational ADC across different tumor types and clinical settings. The companies have not announced a decision to discontinue or continue DYNASTY-Breast02 following the topline findings; instead, they said they would discuss the data and determine the next steps. Further details on the PFS analysis, ILD incidence, fatal events and longer-term OS follow-up would help clarify the candidate’s potential role in HR+/HER2-low metastatic breast cancer. BioNTech is a global biopharmaceutical company developing therapies for cancer and other serious diseases, with an oncology portfolio spanning immunomodulators, ADCs and mRNA-based cancer immunotherapies. DualityBio develops antibody-based therapeutics, including ADC candidates built on its proprietary technology platform. Their collaboration on trastuzumab pamirtecan reflects the continued investigation of HER2-directed ADCs in tumors with varying levels of target expression. The DYNASTY-Breast02 results provide evidence of PFS activity but also raise safety and clinical-benefit considerations that the partners must evaluate before determining the program’s future direction. Trastuzumab pamirtecan remains investigational, and its regulatory status and future availability will depend on further development decisions and applicable regulatory review.
Source:BioNTech,Press release
