A Phase 3, Randomized, Open-label Study Comparing Efficacy and Safety of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) as a Monotherapy and in Combination With Pembrolizumab (MK-3475) Versus Treatment of Physician's Choice in Participants With Previously Untreated Locally Recurrent Unresectable or Metastatic Triple-Negative Breast Cancer Expressing PD-L1 at CPS Less Than 10 (TroFuse-011)

Official 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.

Eligibility Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 1,000 participants

Study Arms

• Arm A: Sacituzumab Tirumotecan (EXPERIMENTAL)
  Participants receive sacituzumab tirumotecan intravenously (IV) at a dose of 4 mg/kg every 2 weeks (Q2W) until disease progression, toxicity or discontinuation.
• Arm B: Sacituzumab Tirumotecan + Pembrolizumab (EXPERIMENTAL)
  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).
• Arm C: Treatment of Physician's Choice (TPC) (ACTIVE_COMPARATOR)
  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.

Interventions

• BIOLOGICAL: Sacituzumab tirumotecan — IV Infusion
• BIOLOGICAL: Pembrolizumab — IV Infusion
• DRUG: Rescue 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).
• DRUG: Paclitaxel — IV Infusion
• DRUG: Nab-paclitaxel — IV Infusion

Primary Outcomes

• Progression-Free Survival (PFS) (sac-TMT versus treatment of physician's choice (TPC); sac-TMT plus pembrolizumab versus TPC) (Up to ~39 months)
• Overall Survival (OS) (sac-TMT versus TPC) (Up to ~61 months)

Secondary Outcomes

• 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)
• Progression-Free Survival (PFS) (sac-TMT plus pembrolizumab versus sac-TMT) (Up to ~39 months)
• Objective Response Rate (ORR) (sac-TMT versus TPC; sac-TMT plus pembrolizumab versus TPC) (Up to ~39 months)
• Duration of Response (DOR) (Up to ~39 months)
• 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)

Eligibility Criteria

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 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 breast cancer
* Has Grade ≥2 peripheral neuropathy
* Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe 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
* Has a history of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids, has current pneumonitis/ILD, or has suspected ILD or pneumonitis that cannot be ruled out by standard diagnostic assessments
* 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 Locations

• USA Mitchell Cancer Institute ( Site 0090), Mobile, Alabama, United States
• Ironwood Cancer & Research Centers ( Site 0036), Chandler, Arizona, United States
• City of Hope ( Site 0097), Duarte, California, United States
• City of Hope Lennar Foundation Cancer Center ( Site 0099), Irvine, California, United States
• UCLA Department of Medicine - Hematology & Oncology ( Site 0047), Los Angeles, California, United States
• UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0016), San Francisco, California, United States
• Yale New Haven Hospital ( Site 0001), New Haven, Connecticut, United States
• Washington Hospital Center ( Site 0098), Washington D.C., District of Columbia, United States
• AdventHealth Medical Group Oncology and Hematology at Altamonte ( Site 0007), Altamonte Springs, Florida, United States
• Florida Cancer Specialists - East ( Site 7000), West Palm Beach, Florida, United States
• ...and 10 more locations

Contact Information

• Toll Free Number — CONTACT
  Phone: 1-888-577-8839
  Email: Trialsites@msd.com

Study Officials

• Medical Director — STUDY_DIRECTOR
  Merck Sharp & Dohme LLC

More Triple Negative Breast Neoplasms Trials

View all Triple Negative Breast Neoplasms clinical trials