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RecruitingInterventionalPhase 3

A Phase III, Multisite, Randomized, Double-Blind Trial of BNT327 in Combination With Chemotherapy Versus Placebo With Chemotherapy in Patients With Previously Untreated Locally Recurrent Inoperable or Metastatic TNBC Determined Ineligible for PD(L)1 Therapy Based on PD-L1 Negative Disease

NCT ID: NCT07173751Sponsor: BioNTech SELast updated: 2026-05-22

Summary

This is a Phase III trial where participants will be randomized to two treatment groups, which means participants will be assigned by equal chance to a treatment group. This trial will be double-blinded, which means neither the participants nor the trial doctors will know which of the two treatments the participants actually receive. Participants will receive either the trial drug with chemotherapy or placebo (which looks like the trial drug but does not have any drug in it) with chemotherapy.

Detailed description

The study consists of a: 1. Screening period (up to 28 days); 2. Treatment period, during which participants will receive pumitamig or placebo in combination with chemotherapy (until disease progression, the occurrence of intolerable toxicity, withdrawal, death, or trial termination \[whichever comes first\]); 3. Safety follow-up (FU) period (for up to 90 days after administration of the last dose of trial treatment) and survival follow-up (until the participant dies, withdraws consent for survival status follow-up, loss of contact, or sponsor decision, whichever occurs first). Participants will be randomized 1:1 to receive either pumitamig in combination with the treatment of physician's choice (TPC) chemotherapy (Arm 1) or placebo in combination with TPC chemotherapy (Arm 2). Chemotherapy will be administered per standard of care. The randomization will be stratified based on the following factors: * Prior treatment with cancer immunotherapy (yes versus no) * On-trial chemotherapy regimen (paclitaxel/nab-paclitaxel versus gemcitabine plus carboplatin versus eribulin) * Geography (East Asia versus the rest of the world \[ROW\]) * PD-L1 status (combined positive score \[CPS\] less than \[\<\] 1 versus 1 less than or equal to \[\<=\] CPS \<10).

Arms & interventions

  • DrugPumitamig

    Solution for intravenous (IV) infusion

  • DrugNab-paclitaxel/Paclitaxel

    IV infusion

  • DrugGemcitabine

    IV infusion

  • DrugCarboplatin

    IV infusion

  • DrugEribulin

    IV infusion

  • DrugMatching placebo

    IV infusion

Outcome measures

Primary

  • Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR)

    PFS is defined as the time from randomization to first documented tumor progression (progressive disease assessed by BICR per response evaluation criteria in solid tumors \[RECIST\] v1.1), or death from any cause, whichever occurs first.

    Time frame: Up to approximately 32 months

  • Overall Survival (OS)

    OS is defined as the time from randomization to death from any cause.

    Time frame: Up to approximately 49 months

Secondary

  • Objective Response Rate (ORR) as Assessed by BICR

    Time frame: Up to approximately 49 months

  • PFS

    Time frame: Up to approximately 32 months

  • ORR

    Time frame: Up to approximately 49 months

  • Duration of Response (DOR)

    Time frame: Up to approximately 49 months

  • Disease Control Rate (DCR)

    Time frame: Up to approximately 32 months

  • PFS Rate as Assessed by BICR

    Time frame: At 6, 12, 18, and 24 months

  • PFS Rate as Assessed by Investigator

    Time frame: At 6, 12, 18, and 24 months

  • OS Rate

    Time frame: At 6, 12, 18, and 24 months

  • Occurrence of Treatment-Emergent Adverse Events (TEAEs) Including Grade Greater than or Equal to (>=) 3, Serious, and Fatal TEAEs by Relationship

    Time frame: From the first dose of study treatment to the 90-days after last dose of study treatment (up to approximately 57 months)

  • Occurrence of Dose Interruption, Reduction, and Discontinuation of Trial Treatment due to TEAEs (including related TEAEs)

    Time frame: From the first dose of study treatment to the 90-days after last dose of study treatment (up to approximately 57 months)

  • Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Core 30 Questionnaire (QLQ-C30) Global Health Status/Quality-of-Life score (Items 29 and 30)

    Time frame: Baseline up to approximately 49 months

  • Change from Baseline in EORTC QLQ-C30 Physical Functioning

    Time frame: Baseline up to approximately 49 months

  • Change from Baseline in Arm Symptoms Scale of EORTC QLQ-Breast Cancer (BR)42

    Time frame: Baseline up to approximately 49 months

  • Change from Baseline in Breast Symptoms Scale of EORTC QLQ-BR42

    Time frame: Baseline up to approximately 49 months

  • Change from Baseline in Functional Assessment of Cancer Therapy-General Version (FACT-G) Overall Bother Item (FACT-GP5)

    Time frame: Baseline up to approximately 49 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: * Are considered ineligible for combination treatment with a monospecific PD(L)1 targeting immunotherapy plus chemotherapy as per their tumor PD-L1 expression status. * Have confirmed locally recurrent inoperable or metastatic TNBC, or estrogen receptor (ER)-low, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (ER and/or progesterone receptor \[PgR\]) 1% to 10%, HER2 immunohistochemistry \[IHC\] 0, 1+, or 2+ with fluorescence in situ hybridization \[FISH\] negative for HER2 gene amplification) documented prior to trial screening as part of standard of care. * Have at least one measurable lesion as the targeted lesion based on RECIST v1.1. * Have provided a tissue sample, archival or fresh, during the screening period (bone biopsies, fine needle aspiration biopsies, and samples from pleural or peritoneal fluid are not acceptable; participants with only one target lesion are not eligible to participate in the trial). * Eastern cooperative oncology group (ECOG) performance status of 0 or 1. Exclusion Criteria: * Have received any of the following therapies or drugs prior to the initiation of trial: * Have received prior systemic anticancer therapy for advanced disease. * Have received prior treatment with a PD(L)-1/vascular endothelial growth factor (VEGF) bispecific antibody. * Have received systemic corticosteroids (at a dosage greater than 10 milligrams \[mg\]/day of prednisone or an equivalent dose of other corticosteroids) within 7 days prior to the initiation of trial treatment. Exception: excluding local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short-term use (\<= 7 days) of corticosteroids for prophylaxis (for example, prevention of contrast agent allergy) or treatment of non-autoimmune conditions (for example, delayed hypersensitivity reactions caused by exposure to allergens). * Have been vaccinated with live attenuated vaccine(s) within 4 weeks prior to initiation of trial treatment. * Have received broad-spectrum intravenous antibiotics therapy within 2 weeks prior to initiation of trial treatment. * Are pregnant or breastfeeding or are planning pregnancy or planning to father children during the trial or within 6 months after the last dose of pumitamig or placebo. * Have undergone major organ surgery, significant trauma, or invasive dental procedures (such as dental implants) within 28 days prior to the initiation of trial treatment or plan to undergo elective surgery during the trial. Placement of vascular infusion devices is allowed. * Have received allogeneic hematopoietic stem cell transplantation or organ transplantation.

Study locations (26)

Highlands Oncology Group

Springdale, Arkansas, 72762

Recruiting

University Of California - San Diego Moores Cancer Center

La Jolla, California, 92037

Recruiting

Cedar Sinai - Samuel Oschin Cancer Center

Los Angeles, California, 90048

Recruiting

Stanford University School of Medicine - Stanford Cancer Institute (SCI) - Stanford Women's Cancer Center

Palo Alto, California, 94304-2201

Recruiting

Sacred Heart Medical Oncology Group

Pensacola, Florida, 32504

Recruiting

Cancer Care Specialists

Decatur, Illinois, 62526

Recruiting

Cancer Care Specialists of Illinois

O'Fallon, Illinois, 62269

Recruiting

Carle Foundation Hospital d/b/a Carle Cancer Center

Urbana, Illinois, 61801

Recruiting

University Medical Center, Inc. DBA University of Louisville Hospital/James Graham Brown Cancer Center

Louisville, Kentucky, 40202

Recruiting

New England Cancer Specialists

Westbrook, Maine, 04092

Recruiting

Saint Agnes Hospital, Clinical Research Center

Baltimore, Maryland, 21229

Recruiting

Lahey Hospital & Medical Center

Burlington, Massachusetts, 01805

Recruiting

Karmanos Cancer Center

Detroit, Michigan, 48201

Recruiting

Profound Research LLC at Michigan Hematology and Oncology Consultants

Royal Oak, Michigan, 48073

Recruiting

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, 64111

Recruiting

Oncology Hematology West, PC dba Nebraska Cancer Specialist

Grand Island, Nebraska, 68803

Recruiting

Paradigm Oncology Hematology West P.C. dba Nebraska Cancer Specialists

Omaha, Nebraska, 68310

Recruiting

Summit Medical Group PA

Florham Park, New Jersey, 07932

Recruiting

Rochester General Hospital Lipson Cancer Institute

Rochester, New York, 14621

Recruiting

Stony Brook University Medical Center

Stony Brook, New York, 11794

Recruiting

Montefiore Medical Center

The Bronx, New York, 10461

Recruiting

Oregon Oncology Specialists

Salem, Oregon, 97301

Recruiting

The West Clinic, P.C. dba West Cancer Center

Germantown, Tennessee, 38002

Recruiting

Oncology Consultants PA

Houston, Texas, 77024

Recruiting

Oncology Consultants PA

Houston, Texas, 77030

Recruiting

Northwest Medical Specialties, PLLC

Tacoma, Washington, 98405

Recruiting