BioNTech, BMS to Pair Pumitamig With Trodelvy in Phase 3 First-Line TNBC Trial

BioNTech and Bristol Myers Squibb (BMS) plan to adapt their phase 3 ROSETTA Breast-01 trial of pumitamig, a PD-L1×VEGF-A bispecific antibody, to combine it with Gilead Sciences’ TROP2-directed antibody-drug conjugate (ADC) sacituzumab govitecan (Trodelvy) in first-line triple-negative breast cancer (TNBC).¹ Pending regulatory approval, the combination will replace the trial’s current pumitamig-plus-chemotherapy regimen in patients with locally advanced or metastatic PD-L1-low or PD-L1-negative TNBC (combined positive score [CPS] <10).¹

“When the ROSETTA Breast-01 trial was initiated, chemotherapy was the only option for patients with PD-L1 negative advanced TNBC,” said Peter Schmid, MD, PhD, lead investigator and director of the Breast Cancer Centre at St. Bartholomew’s Hospital. “While chemotherapy remains a standard first-line option, TROP2-directed ADCs like sacituzumab govitecan are quickly becoming the new global standard of care.”¹

How does pumitamig work?

Pumitamig, also known as BNT327 or BMS986545, is designed to cooperatively bind PD-L1 and VEGF-A.¹ According to BioNTech, the molecule aims to restore the immune system’s ability to recognize and destroy tumor cells while also cutting off the tumor’s blood and oxygen supply through anti-angiogenic activity.¹ The company said that by anchoring to PD-L1 on tumor cells, pumitamig is intended to localize VEGF-A blockade within the tumor microenvironment, which may enhance antitumor activity while limiting systemic exposure.¹

More than 4,000 patients have been treated with pumitamig in clinical trials to date.¹ In lung cancer, interim phase 2 data from the ROSETTA Lung-02 trial showed high response rates with pumitamig plus chemotherapy across PD-L1 expression levels, as BioPharm International® reported in June.

Why add Trodelvy?

The trial change reflects a shift in first-line TNBC treatment. FDA approved Trodelvy on June 24, 2026, as first-line monotherapy for adults with unresectable locally advanced or metastatic TNBC who are not candidates for PD-1 or PD-L1 inhibitor-based therapy, and in combination with pembrolizumab for tumors with PD-L1 CPS ≥10.²

In the Phase 3 ASCENT-03 trial supporting the monotherapy approval, Trodelvy improved median progression-free survival to 9.7 months, compared with 6.9 months for chemotherapy (hazard ratio, 0.62).² The trial enrolled patients who had not previously received systemic therapy for advanced disease and were not eligible for PD-1 or PD-L1 inhibitor therapy.³

“Adapting ROSETTA Breast-01 to reflect the evolving standard of care gives the trial the best chance to inform clinical practice and, ultimately, treatment decisions for patients,” said Özlem Türeci, MD, co-founder and chief medical officer of BioNTech.¹

What are the terms of the collaboration?

Under a clinical trial collaboration and supply agreement, Gilead will supply Trodelvy, while BioNTech will continue to sponsor and lead the trial.¹ BioNTech and BMS are co-developing pumitamig and plan additional phase 3 combination trials in multiple solid tumors.¹ BioNTech noted that the safety and efficacy of the pumitamig and sacituzumab govitecan combination have not been established.¹

In a BioPharm International interview at BIO 2026, Sabeen Mekan, MD, senior vice president and chief medical officer of Zymeworks, discussed why ADC tolerability matters as these therapies are used over longer treatment courses. “The goal is to make cancer a chronic disease,” Mekan said. “Then tolerability becomes very, very important.”

What happens next?

ROSETTA Breast-01 is one of seven ongoing global phase 3 trials of pumitamig, and the drug is also being evaluated in more than 10 Phase 2 novel-novel combination trials, including with ADCs.¹ The phase 3 trial (NCT07173751) plans to enroll 558 patients, with progression-free survival and overall survival as its primary endpoints.⁴

“Combining pumitamig as a potential backbone with complementary modalities such as ADCs is central to our therapeutic approach,” Türeci said.¹

References

1. BioNTech. BioNTech Advances Phase 3 Clinical Trial of Pumitamig in Combination with Gilead’s TROP2-Directed ADC Sacituzumab Govitecan in Triple-Negative Breast Cancer. Press release. GlobeNewswire. Published October 22, 2026. Accessed October 22, 2026.
2. US Food and Drug Administration. FDA approves sacituzumab govitecan-hziy as monotherapy and in combination with pembrolizumab for first-line treatment of triple-negative breast cancer. Published June 24, 2026. Accessed October 22, 2026.
3. Shinkle M. Trodelvy earns FDA approval as first-line treatment for triple-negative breast cancer. Healio. Published June 25, 2026. Accessed October 22, 2026.
4. ClinicalTrials.gov. ROSETTA Breast-01 (NCT07173751). Accessed October 22, 2026.