Triple Negative Breast Neoplasms
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2), Antibody-drug conjugate (ADC), Trophoblast cell-surface antigen 2 (TROP2)
Brief summary
Researchers want to know if sacituzumab tirumotecan given alone or with pembrolizumab can treat triple negative breast cancer (TNBC). The main goal of this study is to learn if people treated with sacituzumab tirumotecan alone or with pembrolizumab live longer overall or without the cancer growing or spreading compared to people treated with chemotherapy.
Interventions
BIOLOGICALSacituzumab tirumotecan
IV Infusion
BIOLOGICALPembrolizumab
IV Infusion
DRUGRescue Medication
Participants receive the following pre-medications before sacituzumab tirumotecan infusion: Histamine-1 (H1) receptor agonist, histamine-2 (H2) receptor antagonist, acetaminophen or equivalent, dexamethasone or equivalent infusion. Participants are also recommended to receive prophylactic steroid mouthwash (dexamethasone or equivalent).
DRUGPaclitaxel
IV Infusion
DRUGNab-paclitaxel
IV Infusion
DRUGGemcitabine
IV Infusion
DRUGCarboplatin
IV Infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The main inclusion criteria include but are not limited to the following: * Has locally recurrent unresectable or metastatic TNBC that cannot be treated with curative intent * Has not received systemic treatment for locally recurrent unresectable or metastatic breast cancer * Participants previously treated for early-stage breast cancer must have completed all prior therapy for early-stage breast cancer with curative intent at least 6 months before the first disease recurrence * Is a candidate for treatment with pembrolizumab and one of the TPC options: paclitaxel or nab-paclitaxel or gemcitabine + carboplatin * Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline with the exception of alopecia or vitiligo. Participants with endocrine-related AEs who are adequately treated with hormone replacement are eligible * Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load * Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) (sac-TMT versus treatment of physician's choice (TPC); sac-TMT plus pembrolizumab versus TPC) | Up to ~39 months | PFS is defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) based on blinded independent central review (BICR) or death due to any cause, whichever occurs first. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. |
| Overall Survival (OS) (sac-TMT versus TPC) | Up to ~61 months | OS is defined as the time from randomization to death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) (sac-TMT plus pembrolizumab versus treatment of physician's choice (TPC); sac-TMT plus pembrolizumab versus sac-TMT) | Up to ~61 months | OS is defined as the time from randomization to death due to any cause. |
| Progression-Free Survival (PFS) (sac-TMT plus pembrolizumab versus sac-TMT) | Up to ~39 months | PFS is defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on BICR or death due to any cause, whichever occurs first. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. |
| Objective Response Rate (ORR) (sac-TMT versus TPC; sac-TMT plus pembrolizumab versus TPC) | Up to ~39 months | ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 based on BICR. |
| Duration of Response (DOR) | Up to ~39 months | For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 based on BICR, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death, whichever occurs first. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. |
| Change from baseline in global health status/quality of life scores, on the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) (sac-TMT versus TPC; sac-TMT plus pembrolizumab versus TPC) | Baseline and up to ~61 months | The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. |
| Change from baseline in physical functioning score, on the EORTC QLQ-C30 (sac-TMT versus TPC; sac-TMT plus pembrolizumab versus TPC) | Baseline and up to ~61 months | The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better level of physical functioning. |
| Change from baseline in emotional functioning score, on the EORTC QLQ-C30 (sac-TMT versus TPC; sac-TMT plus pembrolizumab versus TPC) | Baseline and up to ~61 months | The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to questions about their emotional functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better level of emotional functioning. |
| Change from baseline in fatigue score, on the EORTC QLQ-C30 (sac-TMT versus TPC; sac-TMT plus pembrolizumab versus TPC) | Baseline and up to ~61 months | The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to questions about their fatigue are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better level of function. |
| Change from baseline in diarrhea score, on the EORTC QLQ-C30 (sac-TMT versus TPC; sac-TMT plus pembrolizumab versus TPC) | Baseline and up to ~61 months | The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "Have you had diarrhea?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better level of function. |
| Number of participants who experience one or more adverse events (AEs) | Up to ~61 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. |
| Number of participants who discontinue study treatment due to an AE | Up to ~61 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, China, Colombia, Czechia, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, New Zealand, Peru, Philippines, Poland, Romania, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed