Brief 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.
Brief Title
ROSETTA Breast-01: The Effects and Safety of Pumitamig in Patients With Triple-Negative Breast Cancer
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).
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).
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
+49 6131 9084
Central Contact Phone Ext
0
Central Contact Email
patients@biontech.de
Completion Date
Completion Date Type
Estimated
Conditions
Breast Neoplasms
Eligibility Criteria
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.
* 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.
Inclusion Criteria
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.
* 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.
Gender
All
Gender Based
false
Keywords
Metastatic TNBC
Bispecific antibody
Programmed death-ligand 1 (PD-L1)
Immunotherapy
Immunotherapy in combination with chemotherapy
Combination with other investigational agents
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT07173751
Org Class
Industry
Org Full Name
BioNTech SE
Org Study Id
BNT327-05
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR)
Outcome Time Frame
Up to approximately 32 months
Outcome Description
OS is defined as the time from randomization to death from any cause.
Outcome Measure
Overall Survival (OS)
Outcome Time Frame
Up to approximately 49 months
Secondary Ids
Secondary Id
2025-521884-12-00
Secondary Outcomes
Outcome Description
ORR is defined as the percentage of participants in whom a confirmed complete response (CR) or confirmed partial response (PR) as per RECIST v1.1 is assessed by BICR as best overall response.
Outcome Time Frame
Up to approximately 49 months
Outcome Measure
Objective Response Rate (ORR) as Assessed by BICR
Outcome Description
PFS is defined as the time from randomization to first documented tumor progression (progressive disease assessed by investigator per RECIST v1.1), or death from any cause, whichever occurs first.
Outcome Time Frame
Up to approximately 32 months
Outcome Measure
PFS
Outcome Description
ORR is defined as the percentage of participants in whom a confirmed CR or confirmed PR (per RECIST v1.1) is observed as best overall response.
Outcome Time Frame
Up to approximately 49 months
Outcome Measure
ORR
Outcome Description
DOR is 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.
Outcome Time Frame
Up to approximately 49 months
Outcome Measure
Duration of Response (DOR)
Outcome Description
DCR is defined as the percentage of participants in whom a confirmed CR or confirmed PR or stable disease (SD) (per RECIST v1.1, SD assessed at least 6 weeks after randomization) is observed as best overall response.
Outcome Time Frame
Up to approximately 32 months
Outcome Measure
Disease Control Rate (DCR)
Outcome Time Frame
At 6, 12, 18, and 24 months
Outcome Measure
PFS Rate as Assessed by BICR
Outcome Time Frame
At 6, 12, 18, and 24 months
Outcome Measure
PFS Rate as Assessed by Investigator
Outcome Time Frame
At 6, 12, 18, and 24 months
Outcome Measure
OS Rate
Outcome Description
TEAEs graded according to United Stated (US) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0)
Outcome Time Frame
From the first dose of study treatment to the 90-days after last dose of study treatment (up to approximately 57 months)
Outcome Measure
Occurrence of Treatment-Emergent Adverse Events (TEAEs) Including Grade Greater than or Equal to (>=) 3, Serious, and Fatal TEAEs by Relationship
Outcome Time Frame
From the first dose of study treatment to the 90-days after last dose of study treatment (up to approximately 57 months)
Outcome Measure
Occurrence of Dose Interruption, Reduction, and Discontinuation of Trial Treatment due to TEAEs (including related TEAEs)
Outcome Description
Global health status or quality of life (QoL) scale ranges in score from 0 to 100 with a high scale score representing a higher response level (for example, high score for global health status/QoL is high QoL: high score for symptom scale/item is high symptomatology or problems).
Outcome Time Frame
Baseline up to approximately 49 months
Outcome Measure
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)
Outcome Description
Physical functioning scale ranges in score from 0 to 100 with a high scale score representing a higher response level (for example, high score for functional scale is high/healthy level of functioning).
Outcome Time Frame
Baseline up to approximately 49 months
Outcome Measure
Change from Baseline in EORTC QLQ-C30 Physical Functioning
Outcome Description
Arm symptom scale ranges in score from 0 to 100 with a high scale score representing a higher level of symptoms or problems.
Outcome Time Frame
Baseline up to approximately 49 months
Outcome Measure
Change from Baseline in Arm Symptoms Scale of EORTC QLQ-Breast Cancer (BR)42
Outcome Description
Breast symptom scale ranges in score from 0 to 100 with a high scale score representing a higher level of symptoms or problems.
Outcome Time Frame
Baseline up to approximately 49 months
Outcome Measure
Change from Baseline in Breast Symptoms Scale of EORTC QLQ-BR42
Outcome Description
The single-item GP5, that is "I am bothered by side effects of treatment," is rated on a 5-point Likert scale (where 1=not at all and 5=very much) by the participants. A high scale score represents worse outcome.
Outcome Time Frame
Baseline up to approximately 49 months
Outcome Measure
Change from Baseline in Functional Assessment of Cancer Therapy-General Version (FACT-G) Overall Bother Item (FACT-GP5)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Della Makower
Investigator Email
DMAKOWER@montefiore.org
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Breast Cancer --- BREAST NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Breast Cancer --- BREAST DISEASES
MeSH Terms
BREAST NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
BREAST DISEASES
SKIN DISEASES
SKIN AND CONNECTIVE TISSUE DISEASES
130-NM ALBUMIN-BOUND PACLITAXEL
GEMCITABINE
CARBOPLATIN
ERIBULIN
HETEROCYCLIC COMPOUNDS
DEOXYCYTIDINE
CYTIDINE
PYRIMIDINE NUCLEOSIDES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
COORDINATION COMPLEXES
ORGANIC CHEMICALS