BioNTech and Bristol Myers Squibb Report Promising Phase 2 Results for Pumitamig in Triple-Negative Breast Cancer
核心洞察
BioNTech and Bristol Myers Squibb (搜索) announced encouraging Phase 2 interim data for pumitamig (搜索) (BNT327), a bispecific antibody targeting PD-L1 (搜索) and VEGF-A (搜索), showing a 61.5% confirmed objective response rate in advanced triple-negative breast cancer (搜索) patients.
The investigational therapy demonstrated efficacy across PD-L1 (搜索) expression levels, including in PD-L1 low or negative patients who typically have limited treatment options beyond chemotherapy alone.
Results support the ongoing Phase 3 ROSETTA BREAST-01 trial, which aims to establish pumitamig (搜索) as a new treatment paradigm for PD-L1 (搜索)-negative triple-negative breast cancer (搜索) patients historically excluded from immunotherapy regimens.
BioNTech and Bristol Myers Squibb (搜索) have reported encouraging interim results from a global Phase 2 trial evaluating pumitamig (搜索) (BNT327/BMS986545 (搜索)), an investigational bispecific antibody, in patients with locally advanced or metastatic triple-negative breast cancer (搜索) (TNBC (搜索)). The data, presented at the 2025 San Antonio Breast Cancer Symposium, showed a confirmed objective response rate of 61.5% and disease control rate of 92.3% when combined with chemotherapy, regardless of PD-L1 (搜索) expression levels.
Addressing Critical Unmet Need in TNBC
Triple-negative breast cancer (搜索) represents one of the most aggressive breast cancer subtypes, defined by the absence of estrogen receptor, progesterone receptor, and HER2 expression. The disease accounts for 10-15% of all invasive breast cancer cases and carries a particularly poor prognosis, with a 5-year survival rate of just 15% in advanced stages.
"Triple-negative breast cancer (搜索) is a highly aggressive disease with a poor prognosis and 5-year survival rate of just 15% in advanced stages. There remains an urgent need for new treatment options – particularly for patients with PD-L1 (搜索) low or negative tumors (CPS<10), a subgroup for whom the current standard of care is chemotherapy alone and existing PD-(L)1 inhibitors have historically shown limited benefit," said Peter Schmid, M.D., Ph.D., Lead Investigator and Director of the Breast Cancer Centre at St. Bartholomew's Hospital, London, UK.
Phase 2 Trial Results
The global randomized Phase 2 trial (NCT06449222) evaluated pumitamig (搜索) at two dose levels in combination with four different chemotherapeutic agents for first- and second-line treatment of locally advanced/metastatic TNBC (搜索). The interim analysis included 74 patients, with key efficacy data from 39 evaluable patients in Cohort 1 who received pumitamig plus nab-paclitaxel.
Among the 39 efficacy-evaluable patients, pumitamig (搜索) plus chemotherapy achieved:
- Confirmed objective response rate (cORR): 61.5% (24/39)
- Unconfirmed objective response rate (uORR): 71.8% (28/39)
- Disease control rate (DCR): 92.3% (36/39)
- Progression-free survival rate at 9 months: 59.3%
The efficacy was consistent across dose levels, PD-L1 (搜索) expression levels, and lines of treatment. Higher doses correlated with improved response rates, with unconfirmed ORR of 63.2% at the 15 mg/kg dose and 80.0% at the 20 mg/kg dose. Notably, efficacy was maintained regardless of PD-L1 status, with uORR of 70.6% in both CPS ≥10 and CPS <10 patient populations.
Safety Profile
Pumitamig (搜索) demonstrated a manageable safety profile across both cohorts and all four chemotherapy regimens tested. Grade ≥3 treatment-related adverse events were reported in 17/40 (42.5%) patients in Cohort 1 and 13/34 (38.2%) patients in Cohort 2. Importantly, no pumitamig-related deaths were reported during the study period.
Novel Bispecific Mechanism
Pumitamig (搜索) represents a novel approach combining two validated oncology mechanisms in a single molecule. The bispecific antibody simultaneously targets PD-L1 (搜索) checkpoint inhibition to restore T-cell function and VEGF-A (搜索) neutralization to reverse immunosuppressive effects in the tumor microenvironment while cutting off blood and oxygen supply to tumor cells.
"We are encouraged by these first locally advanced/metastatic TNBC (搜索) data from a global patient population that indicate the potential of pumitamig (搜索) in patients with advanced TNBC irrespective of PD-L1 (搜索) status," said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. "The activity we see in TNBC is consistent with findings in other solid tumors and further supports the pan-tumor potential of pumitamig."
Advancing to Phase 3 Registration Trial
The encouraging Phase 2 results support the ongoing Phase 3 ROSETTA BREAST-01 trial (NCT07173751), a randomized, double-blind, placebo-controlled study designed to evaluate pumitamig (搜索) plus chemotherapy versus placebo plus chemotherapy in 558 patients with previously untreated locally advanced/metastatic TNBC (搜索) who are ineligible for PD-(L)1 therapy due to PD-L1 (搜索) negative disease.
"These data add to the growing evidence from global pumitamig (搜索) studies across multiple indications," said Anne Kerber, Senior Vice President, Head of Development, Hematology, Oncology, Cell Therapy at Bristol Myers Squibb (搜索). "The encouraging results are especially meaningful in patients with PD-L1 (搜索) low or negative tumors (CPS<10), representing the potential of pumitamig to deliver meaningful benefit across PD-L1 expression levels, including patients who historically have had fewer effective treatments."
Broader Development Program
More than 1,400 patients have been treated with pumitamig (搜索) in clinical trials to date. The compound is being evaluated in more than 20 clinical trials as monotherapy or in combination with other treatment modalities across more than 10 solid tumor indications. Five global registrational trials are ongoing or planned, including studies in small cell lung cancer, non-small cell lung cancer, microsatellite stable colorectal cancer, and gastric cancer, in addition to the TNBC (搜索) program.