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RecruitingInterventionalPhase 3

An Open-label, Randomized Phase 3 Study of MK-2870 as a Single Agent and in Combination With Pembrolizumab Versus Treatment of Physician's Choice in Participants With HR+/HER2- Unresectable Locally Advanced or Metastatic Breast Cancer

NCT ID: NCT06312176Sponsor: Merck Sharp & Dohme LLCLast updated: 2026-06-08

Summary

The purpose of this study is to compare sacituzumab tirumotecan as a single agent, and in combination with pembrolizumab, versus Treatment of Physician's Choice (TPC) in participants with hormone receptor positive/human epidermal growth factor receptor-2 negative (HR+/HER2-) unresectable locally advanced, or metastatic, breast cancer. The primary hypotheses are that sacituzumab tirumotecan as a single agent and sacituzumab tirumotecan plus pembrolizumab are superior to TPC with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR) in all participants.

Arms & interventions

  • DrugSacituzumab tirumotecan

    IV infusion

  • BiologicalPembrolizumab

    IV infusion

  • DrugPaclitaxel

    IV infusion

  • DrugNab-paclitaxel

    IV infusion

  • DrugCapecitabine

    oral tablet

  • DrugLiposomal doxorubicin

    IV infusion

Outcome measures

Primary

  • Progression-Free Survival (PFS) ( sacituzumab tirumotecan versus treatment of physician's choice [TPC]; pembrolizumab + sacituzumab tirumotecan versus TPC)

    PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). 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. PFS as assessed by blinded independent central review (BICR) will be presented.

    Time frame: Up to ~38 months

Secondary

  • Overall Survival (OS)

    Time frame: Up to ~77 months

  • Progression-Free Survival (PFS) (pembrolizumab + sacituzumab tirumotecan + versus sacituzumab tirumotecan)

    Time frame: Up to ~57 months

  • Objective Response Rate (ORR)

    Time frame: Up to ~57 months

  • Duration of Response (DOR)

    Time frame: Up to ~57 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)

    Time frame: Baseline and up to ~77 months

  • Change from baseline in physical functioning score, on the EORTC QLQ-C30

    Time frame: Baseline and up to ~77 months

  • Change from baseline in emotional functioning score, on the EORTC QLQ-C30

    Time frame: Baseline and up to ~77 months

  • Change from baseline in fatigue score, on the EORTC QLQ-C30

    Time frame: Baseline and up to ~77 months

  • Change from baseline in diarrhea score, on the EORTC QLQ-C30

    Time frame: Baseline and up to ~77 months

  • Time to first Deterioration (TTD) in global health status/quality of life scores, on the EORTC QLQ-C30

    Time frame: Up to ~77 months

  • TTD in physical functioning score, on the EORTC QLQ-C30

    Time frame: Up to ~77 months

  • TTD in emotional functioning score, on the EORTC QLQ-C30

    Time frame: Up to ~77 months

  • TTD in fatigue score, on the EORTC QLQ-C30

    Time frame: Up to ~77 months

  • TTD in diarrhea score, on the EORTC QLQ-C30

    Time frame: Up to ~77 months

  • Number of participants who experience one or more adverse events (AEs)

    Time frame: Up to ~77 months

  • Number of participants who discontinue study treatment due to an AE

    Time frame: Up to ~77 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: * Has unresectable locally advanced or metastatic centrally-confirmed hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer * Has radiographic disease progression on one or more lines of endocrine therapy for unresectable locally advanced/metastatic HR+/HER2- breast cancer, with one in combination with a CDK4/6 inhibitor * Is a chemotherapy candidate * Has an eastern cooperative oncology group (ECOG) performance status of 0 to 1 assessed within 7 days before randomization * Has adequate organ function * Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy * Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load * Participants with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable Exclusion Criteria: * Has breast cancer amenable to treatment with curative intent * Has experienced an early recurrence (\<6 months after completing adjuvant/neoadjuvant chemotherapy) and therefore is eligible to receive second-line (2L) treatment * Has symptomatic advanced/metastatic visceral spread at risk of rapidly evolving into life-threatening complications * Has received prior chemotherapy for unresectable locally advanced or metastatic breast cancer * Active autoimmune disease that has required systemic treatment in the past 2 years * History of (noninfectious) pneumonitis/interstitial lung disease that requires steroids, or has current pneumonitis/interstitial lung disease * Has an active infection requiring systemic therapy

Study locations (46)

Ironwood Cancer & Research Centers ( Site 0066)

Chandler, Arizona, 85224

Recruiting
Study Coordinator · Contact

Banner MD Anderson Cancer Center-Oncology ( Site 0004)

Gilbert, Arizona, 85234

Recruiting
Study Coordinator · Contact

Providence Medical Foundation-Oncology ( Site 0020)

Fullerton, California, 92835

Recruiting
Study Coordinator · Contact

Moores Cancer Center ( Site 0059)

La Jolla, California, 92093-0698

Active Not Recruiting

Cancer and Blood Specialty Clinic ( Site 0001)

Los Alamitos, California, 90720

Recruiting
Study Coordinator · Contact

University of Colorado Anschutz Medical Campus ( Site 0061)

Aurora, Colorado, 80045

Recruiting
Study Coordinator · Contact

UCHealth Cherry Creek Medical Center ( Site 0094)

Denver, Colorado, 80206

Recruiting
Study Coordinator · Contact

University of Colorado Health - Highlands Ranch Hospital ( Site 0095)

Highlands Ranch, Colorado, 80129

Recruiting
Study Coordinator · Contact

Yale Cancer Center ( Site 0060)

New Haven, Connecticut, 06510

Recruiting
Study Coordinator · Contact

Stamford Hospital ( Site 0049)

Stamford, Connecticut, 06902

Recruiting
Study Coordinator · Contact

AdventHealth Altamonte Springs ( Site 0021)

Altamonte Springs, Florida, 32701

Recruiting
Study Coordinator · Contact

University of Florida College of Medicine ( Site 0063)

Gainesville, Florida, 32610

Recruiting
Study Coordinator · Contact

Orlando Health Cancer Institute ( Site 0011)

Orlando, Florida, 32806

Recruiting
Study Coordinator · Contact

Archbold Memorial Hospital-Lewis Hall Singletary Oncology Center ( Site 0032)

Thomasville, Georgia, 31792

Recruiting
Study Coordinator · Contact

Rush University Medical Center ( Site 0079)

Chicago, Illinois, 60607

Recruiting
Study Coordinator · Contact

University of Chicago Medical Center ( Site 0067)

Chicago, Illinois, 60637

Recruiting
Study Coordinator · Contact

Saint Elizabeth Medical Center Edgewood-Cancer Care Center ( Site 0053)

Edgewood, Kentucky, 41017

Recruiting
Study Coordinator · Contact

Mary Bird Perkins Cancer Center-Breast & GYN Pavilion ( Site 0042)

Baton Rouge, Louisiana, 70817

Recruiting
Study Coordinator · Contact

Greenebaum Comprehensive Cancer Center ( Site 0036)

Baltimore, Maryland, 21201

Recruiting
Study Coordinator · Contact

Mercy Medical Center - Baltimore-Medical Oncology and Hematology ( Site 0028)

Baltimore, Maryland, 21202

Completed

Holy Cross Hospital ( Site 0073)

Silver Spring, Maryland, 20910

Recruiting
Study Coordinator · Contact

Dana-Farber Cancer Institute-Breast Oncology Center ( Site 0037)

Boston, Massachusetts, 02215

Recruiting
Study Coordinator · Contact

Henry Ford Health ( Site 0002)

Detroit, Michigan, 48202

Recruiting
Study Coordinator · Contact

Saint Luke's Cancer Institute ( Site 0027)

Kansas City, Missouri, 64111

Recruiting
Study Coordinator · Contact

Washington University School of Medicine ( Site 0076)

St Louis, Missouri, 63110

Recruiting
Study Coordinator · Contact

NYU Langone Health - Brooklyn ( Site 0089)

Brooklyn, New York, 11220

Recruiting
Study Coordinator · Contact

NYU Langone Hospital - Long Island ( Site 0090)

Mineola, New York, 11501

Recruiting
Study Coordinator · Contact

Laura and Isaac Perlmutter Cancer Center-Hematology and Oncology ( Site 0068)

New York, New York, 10016

Recruiting
Study Coordinator · Contact

Hematology Oncology Associates of Rockland ( Site 0054)

Nyack, New York, 10960

Recruiting
Study Coordinator · Contact

Stony Brook University-Cancer Center ( Site 0034)

Stony Brook, New York, 11794

Recruiting
Study Coordinator · Contact

Levine Cancer Institute ( Site 0014)

Charlotte, North Carolina, 28204

Recruiting
Study Coordinator · Contact

Zangmeister Cancer Center ( Site 7000)

Columbus, Ohio, 43219

Completed

Providence Portland Medical Center ( Site 0044)

Portland, Oregon, 97213

Recruiting
Study Coordinator · Contact

Providence St. Vincent Medical Center ( Site 0081)

Portland, Oregon, 97225

Recruiting
Study Coordinator · Contact

Thomas Jefferson University - Clinical Research Institute ( Site 0056)

Philadelphia, Pennsylvania, 19107

Recruiting
Study Coordinator · Contact

Texas Oncology-Dallas Presbyterian Hospital ( Site 8000)

Dallas, Texas, 75231

Recruiting
Study Coordinator · Contact

Parkland Health and Hospital System ( Site 0069)

Dallas, Texas, 75235

Recruiting
Study Coordinator · Contact

UT Southwestern Medical Center ( Site 0050)

Dallas, Texas, 75390

Recruiting
Study Coordinator · Contact

The Center for Cancer and Blood Disorders ( Site 0041)

Fort Worth, Texas, 76104

Recruiting
Study Coordinator · Contact

Texas Oncology - San Antonio ( Site 8002)

San Antonio, Texas, 78240

Recruiting
Study Coordinator · Contact

The University of Texas Health Science Center at Tyler dba UT Health East Texas HOPE Cancer Center ( Site 0057)

Tyler, Texas, 75701

Recruiting
Study Coordinator · Contact

Inova Schar Cancer Institute ( Site 0025)

Fairfax, Virginia, 22031

Recruiting
Study Coordinator · Contact

Bon Secours St. Francis Medical Center-Oncology Research ( Site 0015)

Midlothian, Virginia, 23114

Recruiting
Study Coordinator · Contact

VCU Health Adult Outpatient Pavillion ( Site 0070)

Richmond, Virginia, 23219

Recruiting
Study Coordinator · Contact

Oncology and Hematology Associates of Southwest Virginia (BRCC) ( Site 8001)

Roanoke, Virginia, 24014

Recruiting
Study Coordinator · Contact

University Hospital and UW Health Clinics-Carbone Cancer Center ( Site 0040)

Madison, Wisconsin, 53792

Recruiting
Study Coordinator · Contact
A Study of Sacituzumab Tirumotecan (MK-2870) as a Single Agent and in Combination With Pembrolizumab (MK-3475) Versus Treatment of Physician's Choice in Participants With HR+/HER2- Unresectable Locally Advanced or Metastatic Breast Cancer (MK-2870-010) | Cancerify