ROSETTA Breast-01: The effects and safety of pumitamig in patients with triple-negative breast cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

BioNTech SE

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Mar 2026 → ongoing

Decision date (initial)

2026-03-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2025-521884-12-00

ClinicalTrials.gov

NCT07173751

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To compare overall survival (OS) in patients treated with pumitamig in combination with chemotherapy versus placebo plus chemotherapy in the intent-to-treat (ITT) set. To compare progression-free survival (PFS) in patients treated with pumitamig in combination with chemotherapy versus placebo plus chemotherapy as assessed by blinded independent central review (BICR) in the ITT set.

Secondary objectives 7

1. To compare the objective response rate (ORR) in patients treated with pumitamig in combination with chemotherapy versus placebo plus chemotherapy as assessed by BICR in the ITT set.
2. To evaluate progression-free survival (PFS) in patients treated with pumitamig in combination with chemotherapy compared to placebo plus chemotherapy as assessed by investigator in the ITT set.
3. To evaluate antitumor activity using the objective response rate (ORR) in patients treated with pumitamig in combination with chemotherapy compared to placebo plus chemotherapy in the ITT set as assessed by the investigator.
4. To evaluate antitumor activity using the duration of response (DOR), and the disease control rate (DCR) in patients treated with pumitamig in combination with chemotherapy compared to placebo plus chemotherapy in the ITT set as assessed by BICR and by the investigator.
5. To evaluate the progression-free survival (PFS) rate and overall survival (OS) rate at fixed timepoints in each treatment arm for the ITT set.
6. To evaluate the safety and tolerability of pumitamig in combination with chemotherapy for the safety analysis population.
7. To evaluate PRO scores of quality-of-life by treatment arm using the EORTC QLQ-C30, QLQ-BR42, and FACT-GP5 for the ITT set.

Conditions and MedDRA coding

First line triple-negative breast cancer (TNBC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Adults, of 18 years of age or older at the time of giving informed consent. Local laws will be followed if the age of consent is older.
2. Are considered ineligible for combination treatment with a monospecific PD(L)1 targeting immunotherapy plus chemotherapy as per their tumor PD-L1 expression status.
3. Have confirmed locally recurrent inoperable or metastatic TNBC, or ER-low, HER2-negative breast cancer documented prior to trial screening as part of standard of care and whose disease status aligns the detailed description in the protocol.
4. Have at least one measurable lesion as the targeted lesion based on RECIST v1.1.
5. Have provided a tissue sample, archival or fresh, during the screening period.
6. ECOG performance status (PS) of 0 or 1.
7. Have adequate organ function in regards to haematology, liver function, kidney function, and coagulation.
8. Are people of child-bearing potential (POCBP) who have a negative serum beta hCG pregnancy test within 7 days of the start of trial treatment.
9. Are POCBP who agree to practice a highly effective form of contraception and to require their male sexual partners to use barrier contraception methods (preferably condoms), starting at the time of giving informed consent and continuously until 6 months after receiving the last dose of pumitamig or placebo.
10. Are men who are sterile or if they are potentially fertile and sexually active with a partner of childbearing potential, who agree to use condoms and to ask their sexual partners to practice a highly effective form of contraception during the trial, starting from the time of giving informed consent and continuously until 6 months after receiving the last dose of pumitamig or placebo.
11. Agree not to donate and/or cryopreserve germ cells (sperm, oocytes, ova) for the purposes of assisted reproduction during trial, from signing the informed consent form and continuously until 6 months after the last dose of pumitamig or placebo.
12. Are able to give informed consent and have given written consent in accordance with ICH GCP and local legislation prior to the start of any trial-specific procedures.
13. Are willing and able to comply with scheduled visits, the treatment schedule, the planned trial assessments (including patient completed diaries) and other requirements of the trial. This includes that they are able to understand and follow trial-related instructions.

Exclusion criteria 23

1. Have received any of the following therapies or drugs prior to the initiation of trial: • prior systemic anticancer therapy for advanced disease. • prior treatment with a PD(L)-1/VEGF bispecific antibody. • systemic corticosteroids within 7 days prior to the initiation of trial treatment. • 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.
2. Have hypertension or diabetic conditions prior to initiation of trial treatment as defined in the study protocol.
3. Have serious non-healing wounds, ulcers, or bone fractures.
4. Have evidence of major coagulation disorders or other significant risks of hemorrhage as defined in the study protocol.
5. Receive therapeutic anticoagulation or antiplatelet therapy.
6. Have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
7. Have a history of serious Grade 3 or higher irAEs that led to treatment discontinuation of a prior immunotherapy or have AEs from prior antitumor therapy that have not returned to Grade 1
8. Have a known or suspected hypersensitivity to the trial treatments including any active ingredient or excipients thereof.
9. Have a known history of human immunodeficiency virus with CD4+ T˗cell counts below 350 cells/µL and with a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections.
10. Have a history of hepatitis B requiring active antiviral therapy.
11. Have a medical, psychological, or social condition which, in the opinion of the investigator, could compromise their wellbeing if they participate in the trial, or that could prevent, limit, or confound the protocol-specified assessments or procedures, or that could impact adherence to protocol described requirements.
12. 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.
13. 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.
14. Have received allogeneic hematopoietic stem cell transplantation or organ transplantation.
15. Have spinal cord compression or central nervous system metastases that are untreated and symptomatic or require treatment with corticosteroids or anticonvulsants for associated-symptom control.
16. Have active autoimmune disease that has required systemic treatment in the past 2 years
17. Have had other malignant tumors within 2 years prior to the trial treatment.
18. Have any heart conditions within 6 months prior to the trial treatment as described in the study protocol.
19. Have an active hepatitis C virus infection.
20. Are a vulnerable individual, i.e., an individual whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.
21. Have superior vena cava syndrome or symptoms of spinal cord compression.
22. Have active, or a history of, pneumonitis requiring treatment with steroids, or active, or a history of, interstitial lung disease.
23. Have a history of tuberculosis that was not successfully treated.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Overall survival (OS) defined as the time from randomization to death from any cause.
2. Progression-free survival (PFS) defined as the time from randomization to first documented tumor progression (assessed by blinded independent central review (BICR) per RECIST v1.1), or death from any cause, whichever occurs first.

Secondary endpoints 15

1. Objective response rate (ORR) defined as the proportion of patients in whom a confirmed complete response (CR) or confirmed partial response (PR) (per RECIST v1.1) is assessed by BICR as best overall response.
2. PFS defined as the time from randomization to first documented tumor progression (assessed by investigator per RECIST v1.1), or death from any cause, whichever occurs first.
3. Objective response rate (ORR) defined as the proportion of patients in whom a confirmed complete response (CR) or confirmed partial response (PR) (per RECIST v1.1) is observed as best overall response.
4. Duration of response (DOR) defined as the time from first objective response (CR or PR per RECIST v1.1) to first occurrence of objective tumor progression (progressive disease per RECIST v1.1), or death from any cause, whichever occurs first
5. Disease control rate (DCR) defined as the proportion of patients in whom a confirmed CR or confirmed PR or SD (per RECIST v1.1, SD assessed at least 6 weeks after randomization) is observed as best overall response.
6. Progression-free survival (PFS) rate as assessed by BICR at 6, 12, 18, and 24 months.
7. Progression-free survival (PFS) rate as assessed by investigator at 6, 12, 18, and 24 months.
8. Overall survival (OS) rate at 6, 12, 18, and 24 months.
9. Occurrence of treatment-emergent adverse events (TEAEs) including Grade ≥3 according to NCI CTCAE v5.0, serious, and fatal TEAEs by relationship, from the first dose of pumitamig or placebo to 90 days after last dose of trial treatment.
10. Occurrence of dose interruption, reduction, and discontinuation of trial treatment due to TEAEs (including related TEAEs) from the first dose of pumitamig or placebo to 90 days after last dose of trial treatment.
11. Change from baseline in EORTC Quality of Life (QLQ)-C30 Global Health status / Quality-of-Life score (Items 29 and 30).
12. Change from baseline in EORTC QLQ-C30 physical functioning.
13. Change from baseline in arm symptoms scale of the EORTC QLQ-BR42.
14. Change from baseline in breast symptoms scale of the EORTC QLQ-BR42.
15. Change from baseline in the Functional Assessment of Cancer Therapy - General (FACT-G) overall bother item (FACT-GP5).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

BioNTech SE

Sponsor organisation

BioNTech SE

Address

An Der Goldgrube 12, Oberstadt Oberstadt

City

Mainz

Postcode

55131

Country

Germany

Scientific contact point

Organisation

BioNTech SE

Contact name

Clinical Trial Information Desk

Public contact point

Organisation

BioNTech SE

Contact name

Clinical Trial Information Desk

Third parties 11

Locations

8 EU/EEA countries · 72 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 186 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications