A Study of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Triple-Negative Breast Cancer (MK-2870-011/TroFuse-011)
- Conditions
- Triple Negative Breast Neoplasms
- Interventions
- Registration Number
- NCT06841354
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1000
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 TNBC
- 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 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
The main exclusion criteria include but are not limited to the following:
- Has breast cancer amenable to treatment with curative intent
- Has TNBC with evaluable tumor programmed death ligand 1 (PD-L1) expression at combined positive score (CPS) ≥10
- Has received prior systemic therapy for treatment of locally recurrent unresectable or metastatic TNBC
- Has Grade ≥2 peripheral neuropathy
- Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing
- Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
- Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
- Has skin only metastatic disease
- Has advanced/metastatic, symptomatic visceral spread at risk of rapidly evolving into life-threatening complications
- Human immunodeficiency virus (HIV)-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- Has known additional malignancy that is progressing or has required active treatment within the past 5 years
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable
- Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed
- History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV deoxyribonucleic acid (DNA)) and Hepatitis C virus (HCV) (defined as anti-HCV antibody (Ab) positive and detectable HCV ribonucleic acid (RNA)) infection
- History of stem cell/solid organ transplant
- Has not adequately recovered from major surgery or has ongoing surgical complications
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Sacituzumab Tirumotecan Rescue Medication Participants receive sacituzumab tirumotecan intravenously (IV) at a dose of 4 mg/kg every 2 weeks (Q2W) until disease progression, toxicity or discontinuation. Additionally, participants may receive rescue medication per approved product label, at the discretion of the investigator. Arm B: Sacituzumab Tirumotecan + Pembrolizumab Sacituzumab tirumotecan Participants receive sacituzumab tirumotecan IV 4 mg/kg Q2W until disease progression, toxicity or discontinuation PLUS pembrolizumab IV 400 mg every 6 weeks (Q6W) for up to 18 administrations (up to \~2 years). Additionally, participants may receive rescue medication per approved product label, at the discretion of the investigator. Arm B: Sacituzumab Tirumotecan + Pembrolizumab Pembrolizumab Participants receive sacituzumab tirumotecan IV 4 mg/kg Q2W until disease progression, toxicity or discontinuation PLUS pembrolizumab IV 400 mg every 6 weeks (Q6W) for up to 18 administrations (up to \~2 years). Additionally, participants may receive rescue medication per approved product label, at the discretion of the investigator. Arm B: Sacituzumab Tirumotecan + Pembrolizumab Rescue Medication Participants receive sacituzumab tirumotecan IV 4 mg/kg Q2W until disease progression, toxicity or discontinuation PLUS pembrolizumab IV 400 mg every 6 weeks (Q6W) for up to 18 administrations (up to \~2 years). Additionally, participants may receive rescue medication per approved product label, at the discretion of the investigator. Arm C: Treatment of Physician's Choice (TPC) Paclitaxel Participants receive physician's choice of chemotherapy agent(s): paclitaxel IV 80 mg/m\^2 once every week (Q1W) OR paclitaxel IV 90 mg/m\^2 on Days 1, 8, and 15, every 4 weeks (Q4W) OR nab-paclitaxel IV 100 mg/m\^2 on Days 1, 8, and 15, Q4W OR gemcitabine IV 1000 mg/m\^2 on Days 1 and 8, every 3 weeks (Q3W) PLUS carboplatin IV area under the curve (AUC) 2 mg/mL/min on Days 1 and 8, Q3W, until disease progression, toxicity or discontinuation. Arm C: Treatment of Physician's Choice (TPC) Nab-paclitaxel Participants receive physician's choice of chemotherapy agent(s): paclitaxel IV 80 mg/m\^2 once every week (Q1W) OR paclitaxel IV 90 mg/m\^2 on Days 1, 8, and 15, every 4 weeks (Q4W) OR nab-paclitaxel IV 100 mg/m\^2 on Days 1, 8, and 15, Q4W OR gemcitabine IV 1000 mg/m\^2 on Days 1 and 8, every 3 weeks (Q3W) PLUS carboplatin IV area under the curve (AUC) 2 mg/mL/min on Days 1 and 8, Q3W, until disease progression, toxicity or discontinuation. Arm C: Treatment of Physician's Choice (TPC) Gemcitabine Participants receive physician's choice of chemotherapy agent(s): paclitaxel IV 80 mg/m\^2 once every week (Q1W) OR paclitaxel IV 90 mg/m\^2 on Days 1, 8, and 15, every 4 weeks (Q4W) OR nab-paclitaxel IV 100 mg/m\^2 on Days 1, 8, and 15, Q4W OR gemcitabine IV 1000 mg/m\^2 on Days 1 and 8, every 3 weeks (Q3W) PLUS carboplatin IV area under the curve (AUC) 2 mg/mL/min on Days 1 and 8, Q3W, until disease progression, toxicity or discontinuation. Arm C: Treatment of Physician's Choice (TPC) Carboplatin Participants receive physician's choice of chemotherapy agent(s): paclitaxel IV 80 mg/m\^2 once every week (Q1W) OR paclitaxel IV 90 mg/m\^2 on Days 1, 8, and 15, every 4 weeks (Q4W) OR nab-paclitaxel IV 100 mg/m\^2 on Days 1, 8, and 15, Q4W OR gemcitabine IV 1000 mg/m\^2 on Days 1 and 8, every 3 weeks (Q3W) PLUS carboplatin IV area under the curve (AUC) 2 mg/mL/min on Days 1 and 8, Q3W, until disease progression, toxicity or discontinuation. Arm A: Sacituzumab Tirumotecan Sacituzumab tirumotecan Participants receive sacituzumab tirumotecan intravenously (IV) at a dose of 4 mg/kg every 2 weeks (Q2W) until disease progression, toxicity or discontinuation. Additionally, participants may receive rescue medication per approved product label, at the discretion of the investigator.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) (sac-TMT versus treatment of physician's choice (TPC); sac-TMT plus pembrolizumab versus TPC) Up to ~37 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 Outcome Measures
Name Time Method 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 ~37 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 ~37 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 ~37 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.
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Trial Locations
- Locations (6)
Comprehensive Cancer Centers of Nevada ( Site 0015)
🇺🇸Las Vegas, Nevada, United States
Renown Regional Medical Center ( Site 0005)
🇺🇸Reno, Nevada, United States
Rambam Health Care Campus ( Site 3700)
🇮🇱Haifa, Israel
Rabin Medical Center ( Site 3702)
🇮🇱Petah Tikva, Israel
Sheba Medical Center ( Site 3701)
🇮🇱Ramat Gan, Israel
National Cheng Kung University Hospital ( Site 5304)
🇨🇳Tainan, Taiwan