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)

Merck Sharp & Dohme (MSD)

Status and phase: Enrolling; Phase 3

Conditions: Triple Negative Breast Neoplasms

Treatments: Biological: Pembrolizumab; Drug: Paclitaxel; Drug: Nab-paclitaxel; Drug: Gemcitabine; Biological: Sacituzumab tirumotecan; Drug: Rescue Medication; Drug: Carboplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT06841354

U1111-1311-2310 (Registry Identifier)

TroFuse-011 (Other Identifier)

2024-516834-36-00 (Registry Identifier)

MK-2870-011 (Other Identifier)

2870-011

Details and patient eligibility

About

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.

Enrollment: 1,000 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 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

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,000 participants in 3 patient groups

Arm A: Sacituzumab Tirumotecan

Experimental group

Description:

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.

Treatment:

Drug: Rescue Medication

Biological: Sacituzumab tirumotecan

Arm B: Sacituzumab Tirumotecan + Pembrolizumab

Experimental group

Description:

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.

Treatment:

Drug: Rescue Medication

Biological: Sacituzumab tirumotecan

Biological: Pembrolizumab

Arm C: Treatment of Physician's Choice (TPC)

Active Comparator group

Description:

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.

Treatment:

Drug: Carboplatin

Drug: Gemcitabine

Drug: Nab-paclitaxel

Drug: Paclitaxel