ROSETTA Breast-01: The Effects and Safety of Pumitamig in Patients With Triple-Negative Breast Cancer

BioNTech

Status and phase: Enrolling; Phase 3

Conditions: Breast Neoplasms

Treatments: Drug: Carboplatin; Drug: Matching placebo; Drug: Nab-paclitaxel/Paclitaxel; Drug: Pumitamig; Drug: Gemcitabine; Drug: Eribulin

Study type: Interventional

Funder types: Industry

Identifiers

NCT07173751

BNT327-05

2025-521884-12-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

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.

Full 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).

Enrollment: 558 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

558 participants in 2 patient groups, including a placebo group

Arm 1: Pumitamig + Treatment of Physician's Choice (TPC) Chemotherapy

Experimental group

Description:

Participants will be administered with pumitamig (BNT327) plus chemotherapy regimen.

Treatment:

Drug: Eribulin

Drug: Gemcitabine

Drug: Pumitamig

Drug: Nab-paclitaxel/Paclitaxel

Drug: Carboplatin

Arm 2: Placebo + TPC Chemotherapy

Placebo Comparator group

Description:

Participants will be administered with matching placebo plus chemotherapy regimen.

Treatment:

Drug: Eribulin

Drug: Gemcitabine

Drug: Nab-paclitaxel/Paclitaxel

Drug: Matching placebo

Drug: Carboplatin