BioNTech plans to amend its Phase 3 ROSETTA Breast-01 trial to evaluate pumitamig with Gilead’s Trodelvy in advanced triple-negative breast cancer, pending regulatory approval.
Written By: Aasritha Thippavajjala, PharmD
Reviewed By: Pharmacally Editorial Team
BioNTech SE announced on October 22, 2026, a clinical trial collaboration and supply agreement with Gilead Sciences to evaluate pumitamig in combination with sacituzumab govitecan (Trodelvy) in patients with locally advanced or metastatic PD-L1-low or PD-L1-negative triple-negative breast cancer (TNBC). The companies plan to amend the Phase 3 ROSETTA Breast-01 trial to replace chemotherapy with the antibody-drug conjugate (ADC), subject to regulatory approval. The safety and efficacy of the proposed combination have not been established.
Pumitamig, also known as BNT327 or BMS-986545, is an investigational bispecific immunomodulator jointly developed by BioNTech and Bristol Myers Squibb (BMS). It is designed to bind programmed death-ligand 1 (PD-L1) and vascular endothelial growth factor A (VEGF-A). BioNTech will continue to sponsor and lead the trial, while Gilead will supply sacituzumab govitecan.
ROSETTA Breast-01 Trial Design
ROSETTA Breast-01 (NCT07173751) is a global, randomized, double-blind Phase 3 trial evaluating pumitamig-based treatment in patients with locally advanced or metastatic TNBC with a PD-L1 combined positive score (CPS) below 10. The study was initiated following positive results from a global Phase 2 trial of pumitamig plus chemotherapy, although the latest announcement does not provide detailed efficacy or safety data from that study.
The currently registered trial plans to enroll approximately 558 participants. Its original design compares pumitamig plus physician’s-choice chemotherapy with placebo plus the same chemotherapy. Options include paclitaxel or nab-paclitaxel, gemcitabine plus carboplatin, and eribulin. The primary efficacy measures include progression-free survival (PFS), assessed by blinded independent central review, and overall survival (OS).
Planned Protocol Modification
BioNTech and BMS plan to replace chemotherapy with sacituzumab govitecan, pending regulatory approval. The companies describe ROSETTA Breast-01 as the first global Phase 3 trial designed to evaluate pumitamig in combination with an ADC.
Peter Schmid, M.D., Ph.D., the trial’s lead investigator and director of the Breast Cancer Centre at St. Bartholomew’s Hospital, said treatment options have evolved since the study began, with TROP2-directed ADCs increasingly influencing first-line treatment decisions in advanced TNBC. BioNTech Chief Medical Officer Özlem Türeci, M.D., said the amendment aims to evaluate whether combining pumitamig with sacituzumab govitecan can further improve patient outcomes.
The announcement does not specify the revised comparator arm, whether enrollment or endpoints will change, or when the amended protocol would take effect. The public trial registry continues to describe the original chemotherapy-based design and does not yet list sacituzumab govitecan.
Mechanistic Rationale for the Combination
Pumitamig is designed to combine immune modulation through PD-L1 targeting with VEGF-A inhibition. According to BioNTech, binding to PD-L1 may help localize VEGF-A blockade within the tumor microenvironment. This is a proposed mechanism, not a demonstrated clinical effect of the combination.
Sacituzumab govitecan targets TROP2 and delivers a cytotoxic payload to cancer cells. Combining the ADC with pumitamig is intended to investigate whether these complementary approaches can improve antitumor activity. However, no efficacy, safety, or tolerability results have been reported for the proposed combination.
Clinical Interpretation
The planned amendment reflects an effort to align ROSETTA Breast-01 with the evolving treatment landscape in advanced TNBC. Replacing chemotherapy with sacituzumab govitecan could allow investigators to assess pumitamig alongside an ADC that BioNTech considers increasingly relevant to first-line treatment.
The change also creates an important evidence question: whether adding pumitamig provides a meaningful benefit beyond sacituzumab govitecan alone. The announcement does not establish that benefit, and the earlier Phase 2 results supporting the original trial are not detailed in the release. The clinical significance of the revised design will depend on the final protocol and subsequent efficacy and safety findings.
Regulatory approval remains pending, and no implementation timeline has been disclosed. Until the amended protocol is formally documented, the public registry should be understood as reflecting the original chemotherapy-based study. BioNTech and BMS also plan to explore pumitamig in additional Phase 3 combination trials across multiple solid tumors.
References
BioNTech SE. BioNTech Advances Phase 3 Clinical Trial of Pumitamig in Combination with Gilead’s TROP2-Directed ADC Sacituzumab Govitecan in Triple-Negative Breast Cancer. October 22, 2026.
ClinicalTrials.gov. ROSETTA Breast-01: The Effects and Safety of Pumitamig in Patients with Triple-Negative Breast Cancer. NCT07173751.
About the Writer
Aasritha Thippavajjala (Linkedin) is a pharm D student and aspiring medical writer with medical writing, clinical training experience and a strong interest in clinical research and patient safety She has hands-on exposure to clinical pharmacy activities including medication profile assessment, clinical case review, identification of potential drug-related problems, ADR awareness, patient counselling, and clinical documentation. She has also gained experience in medical literature review, evidence synthesis, and scientific communication through her published review article on digital twin-based patient simulation and her poster presentation at the 74th Indian Pharmaceutical Congress. Certified in ICH Good Clinical Practice (E6(R3)) and Scientific Writing in Health Research, she is passionate about applying her clinical knowledge and research skills to medical writing ,clinical research and contributing to accurate, evidence-based healthcare.