RecruitingInterventionalPhase 3

A Phase 3, Randomized, Open-label Study to Evaluate the Efficacy and Safety of Sac-TMT (Sacituzumab Tirumotecan, MK-2870) Followed by Carboplatin/Paclitaxel vs Chemotherapy, Both in Combination With Pembrolizumab as Neoadjuvant Therapy for High-Risk, Early-Stage, Triple-Negative Breast Cancer or Hormone Receptor-low Positive/Human Epidermal Growth Factor Receptor-2 Negative Breast Cancer

NCT ID: NCT06966700Sponsor: Merck Sharp & Dohme LLCLast updated: 2026-06-12

Summary

Researchers are looking for new ways to treat types of breast cancer that are both: * High-risk, which means the cancer may have a higher chance of getting worse or coming back after treatment * Early-stage, which means the cancer is in the breast or the lymph nodes around the breast The 2 types of breast cancer in this study are triple-negative breast cancer (TNBC) and hormone receptor (HR)-low positive/human epidermal growth factor receptor-2 (HER2) negative breast cancer. These cancers have zero or a low amount of a protein called HER2 and other proteins that attach to the hormones estrogen or progesterone. Sacituzumab tirumotecan (also known as sac-TMT or MK-2870), the study medicine, is a type of targeted therapy. A targeted therapy is a treatment that works to control how specific types of cancer cells grow and spread. The main goals of this study are to learn if people who receive sac-TMT, pembrolizumab, and chemotherapy: * Have fewer cancer cells found in the tumors and lymph nodes removed during surgery compared to those who receive only pembrolizumab and chemotherapy * Live longer without the cancer growing, spreading, or coming back compared to people who receive only pembrolizumab with chemotherapy

Arms & interventions

BiologicalSacituzumab tirumotecan
IV infusion
BiologicalPembrolizumab
IV infusion
DrugRescue Medication
Participants receive rescue medication at the investigators discretion, per approved product label. Recommended rescue medications are histamine -1 (H1) receptor agonist, histamine-2 (H2) receptor antagonist, acetaminophen or equivalent, dexamethasone or equivalent infusion, or steroid mouthwash (dexamethasone or equivalent).
DrugCarboplatin
IV infusion
DrugPaclitaxel
IV infusion
DrugDoxorubicin
IV infusion
DrugEpirubicin
IV infusion
DrugCyclophosphamide
IV infusion
DrugCapecitabine
Oral tablet
DrugOlaparib
Oral tablet

Outcome measures

Primary

Percentage of Participants with Pathological Complete Response (pCR) at the Time of Definitive Surgery
pCR (ypT0/Tis ypN0) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes after completion of neoadjuvant systemic therapy per current American Joint Committee on Cancer (AJCC) staging criteria assessed by the local pathologist at the time of definitive surgery.
Time frame: Up to approximately 30 weeks
Event-Free Survival (EFS)
EFS is defined as the time from randomization to disease progression that precludes surgery, local or distant recurrence, or death due to any cause, whichever occurs first.
Time frame: Up to approximately 92 months

Secondary

Overall Survival (OS)
Time frame: Up to approximately 115 months
Percentage of Participants with pCR with No Ductal Carcinoma in Situ (pCR-no DCIS) at the Time of Definitive Surgery
Time frame: Up to approximately 30 weeks
Percentage of Participants with pCR at the Time of Definitive Surgery (High-risk, early-stage, TNBC subset)
Time frame: Up to approximately 30 weeks
Event-Free Survival (EFS) (High-risk, early-stage, TNBC subset)
Time frame: Up to approximately 92 months
Overall Survival (OS) (High-risk, early-stage, TNBC subset)
Time frame: Up to approximately 115 months
Distant Progression or Distant Recurrence-Free Survival (DPDRFS)
Time frame: Up to approximately 92 months
Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status-Quality of Life Score
Time frame: Baseline and up to approximately 3 years
Change from Baseline in EORTC QLQ-C30 Physical Functioning Score
Time frame: Baseline and up to approximately 3 years
Change from Baseline in EORTC QLQ-C30 Role Functioning Score
Time frame: Baseline and up to approximately 3 years
Change from Baseline in EORTC QLQ-C30 Fatigue Score
Time frame: Baseline and up to approximately 3 years
Change from Baseline in EORTC QLQ Breast Cancer 42 (BR42) Systemic Therapy Side Effects Score
Time frame: Baseline and up to approximately 3 years
Number of Participants Who Experience One or More Adverse Events (AEs)
Time frame: Up to approximately 67 weeks
Number of Participants Who Discontinue Study Treatment Due to an AE
Time frame: Up to approximately 54 weeks

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has previously untreated high-risk, early-stage, non-metastatic (M0) breast cancer (BC), defined as any of the following combined primary tumor (T) and regional lymph node (N) staging per AJCC 8th edition criteria as assessed by the physician investigator based on radiological and/or clinical assessment: * cT1c, N1-N2 * cT2, N0-N2 * cT3, N0-N2 * cT4a-d, N0-N2 * The participant must have a centrally confirmed diagnosis of BC that is triple-negative or HR-low+/HER2- (defined as estrogen receptor (ER)-low+ expression in 1% to 10% cells and HER2- as by the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. * Provides a core needle biopsy from the primary breast tumor at screening to the central laboratory. * Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 28 days before Cycle1 Day 1 (C1D1). * Demonstrates adequate organ function. Exclusion Criteria: The main exclusion criteria include but are not limited to the following: * Metastatic (Stage IV) breast cancer or clinical node stage 3 (cN3) nodal involvement * Has received any prior treatment, including radiation, systemic therapy,and/or definitive surgery for currently diagnosed breast cancer * Has undergone excisional biopsy of the primary tumor, axillary lymph node dissection, and/or axillary sentinel lymph node biopsy prior to study treatment. * Received prior systemic anticancer therapy including investigational agents within 4 weeks before C1D1. * Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX- 40, CD137). * Received prior treatment with a TROP2-targeted antibody-drug conjugate (ADC). * Received prior treatment with a topoisomerase I inhibitor-containing ADC. * Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. * Known additional malignancy that is progressing or has required active treatment within the past 5 years. * Uncontrolled systemic disease. * History of (noninfectious) pneumonitis/interstitial lung disease that required steroids, has current pneumonitis/interstitial lung disease or has suspected interstitial lung disease (ILD) or pneumonitis that cannot be ruled out by standard diagnostic assessments at Screening..

Study locations (53)

Banner MD Anderson Cancer Center ( Site 0066)

Gilbert, Arizona, 85234

Recruiting

Study Coordinator · Contact

480-256-6444

Mayo Clinic Cancer Center ( Site 0034)

Phoenix, Arizona, 85054

Recruiting

Study Coordinator · Contact

480-574-2802

University of Arizona Cancer Center ( Site 0035)

Tucson, Arizona, 85719

Recruiting

Study Coordinator · Contact

520-694-2873

Roy and Patricia Disney Family Cancer Center ( Site 0055)

Burbank, California, 91505

Recruiting

Study Coordinator · Contact

818-840-0921

Providence Medical Foundation ( Site 0080)

Fullerton, California, 92835

Recruiting

Study Coordinator · Contact

714-446-5900

Hoag Memorial Hospital Presbyterian ( Site 0010)

Newport Beach, California, 92663

Recruiting

Study Coordinator · Contact

949-764-4624

Helios Clinical Research ( Site 0061)

Whittier, California, 90602

Recruiting

Study Coordinator · Contact

562-698-6888

Intermountain Health Cancer Center Saint Joseph ( Site 0062)

Denver, Colorado, 80218

Recruiting

Study Coordinator · Contact

303-318-3434

Rocky Mountain Cancer Centers (RMCC) ( Site 8006)

Denver, Colorado, 80220

Recruiting

Study Coordinator · Contact

303-430-2700

Intermountain Health St. Mary's Regional Hospital ( Site 0054)

Grand Junction, Colorado, 81501

Recruiting

Study Coordinator · Contact

970-298-7638

AdventHealth Medical Group Oncology and Hematology at Altamonte ( Site 0044)

Altamonte Springs, Florida, 32701

Recruiting

Study Coordinator · Contact

407-834-5151

Florida Cancer Specialists - South ( Site 7004)

Fort Myers, Florida, 33901

Recruiting

Study Coordinator · Contact

239-274-9930

Bioresearch Partner ( Site 0072)

Hialeah, Florida, 33013

Recruiting

Study Coordinator · Contact

833-489-4968

Mayo Clinic Hospital ( Site 0013)

Jacksonville, Florida, 32224

Recruiting

Study Coordinator · Contact

904-953-7290

Florida Cancer Specialists - North ( Site 7002)

St. Petersburg, Florida, 33701

Recruiting

Study Coordinator · Contact

727-216-1143

City of Hope Cancer Center - Atlanta ( Site 0102)

Newnan, Georgia, 30265

Recruiting

Study Coordinator · Contact

770-400-6000

Fort Wayne Medical Oncology and Hematology ( Site 0084)

Fort Wayne, Indiana, 46804

Recruiting

Study Coordinator · Contact

260-436-0800

Franciscan Health ( Site 0077)

Indianapolis, Indiana, 46237

Recruiting

Study Coordinator · Contact

317-528-7060

Ochsner Clinic Foundation ( Site 0021)

New Orleans, Louisiana, 70121

Recruiting

Study Coordinator · Contact

866-624-7637

Louisiana State University Health Sciences Shreveport ( Site 0053)

Shreveport, Louisiana, 71103

Recruiting

Study Coordinator · Contact

318-626-0000

New England Cancer Specialists ( Site 0051)

Westbrook, Maine, 04092

Recruiting

Study Coordinator · Contact

207-303-3300

Mercy Medical Center - Baltimore ( Site 0015)

Baltimore, Maryland, 21202

Recruiting

Study Coordinator · Contact

410-951-7956

Saint Luke's Cancer Institute ( Site 0059)

Kansas City, Missouri, 64111

Recruiting

Study Coordinator · Contact

816-923-2677

Washington University Siteman Cancer Center ( Site 0031)

St Louis, Missouri, 63110

Recruiting

Study Coordinator · Contact

314-286-2341

Cancer Partners of Nebraska ( Site 0068)

Lincoln, Nebraska, 68516

Recruiting

Study Coordinator · Contact

402-327-7363

Optum Care Cancer Center ( Site 0050)

Las Vegas, Nevada, 89102

Recruiting

Study Coordinator · Contact

702-724-8787

Renown Regional Medical Center ( Site 0041)

Reno, Nevada, 89502

Recruiting

Study Coordinator · Contact

775-982-4000

Hackensack Univ Medical Center (HUMC) ( Site 0007)

Hackensack, New Jersey, 07601

Recruiting

Study Coordinator · Contact

551-996-5855

Rutgers Cancer Institute of New Jersey ( Site 0076)

New Brunswick, New Jersey, 08901

Recruiting

Study Coordinator · Contact

732-253-3939

Altru Health System ( Site 0057)

Grand Forks, North Dakota, 58201

Recruiting

Study Coordinator · Contact

701-780-5451

Good Samaritan Hospital-TriHealth Cancer institute ( Site 0027)

Cincinnati, Ohio, 45220

Recruiting

Study Coordinator · Contact

513-853-1300

Medical University of South Carolina-Hollings Cancer Center ( Site 0016)

Charleston, South Carolina, 29425

Recruiting

Study Coordinator · Contact

843-792-6434

St Francis Cancer Center ( Site 0093)

Greenville, South Carolina, 29607

Recruiting

Study Coordinator · Contact

864-603-6200

Avera McKennan Hospital ( Site 0002)

Sioux Falls, South Dakota, 57105

Recruiting

Study Coordinator · Contact

605-322-3000

Avera Cancer Institute - Yankton ( Site 0089)

Yankton, South Dakota, 57078

Recruiting

Study Coordinator · Contact

605-601-1830

Tennessee Cancer Specialists ( Site 7001)

Knoxville, Tennessee, 37909

Recruiting

Study Coordinator · Contact

865-934-5800

Nashville General Hospital ( Site 0017)

Nashville, Tennessee, 37208

Recruiting

Study Coordinator · Contact

615-341-4383

Vanderbilt-Ingram Cancer Center ( Site 0038)

Nashville, Tennessee, 37232

Recruiting

Study Coordinator · Contact

615-322-2064

Hendrick Medical Center ( Site 0009)

Abilene, Texas, 79601

Recruiting

Study Coordinator · Contact

325-670-2000

Texas Oncology - Northeast Texas ( Site 8002)

Flower Mound, Texas, 75028

Recruiting

Study Coordinator · Contact

972-537-4100

JPS Oncology and Infusion Center ( Site 0083)

Fort Worth, Texas, 76104

Recruiting

Study Coordinator · Contact

817-702-8049

Kelsey-Seybold Clinic ( Site 0042)

Houston, Texas, 77025

Recruiting

Study Coordinator · Contact

713-239-4510

Kelsey-Seybold Clinic ( Site 0088)

Houston, Texas, 77025

Recruiting

Study Coordinator · Contact

713-239-4510

Oncology Consultants P.A. ( Site 0073)

Houston, Texas, 77030

Recruiting

Study Coordinator · Contact

713-275-3233

Texas Tech University Health Sciences Center ( Site 0087)

Lubbock, Texas, 79430

Recruiting

Study Coordinator · Contact

806-743-4222

Texas Oncology - San Antonio ( Site 8004)

San Antonio, Texas, 78240

Recruiting

Study Coordinator · Contact

210-595-5300

Intermountain Medical Center ( Site 0074)

Murray, Utah, 84107

Recruiting

Study Coordinator · Contact

801-507-3630

Bon Secours Cancer Institute at St. Francis ( Site 0048)

Midlothian, Virginia, 23114

Recruiting

Study Coordinator · Contact

804-893-8717

Oncology and Hematology Associates of Southwest Virginia (BRCC) ( Site 8005)

Roanoke, Virginia, 24014

Recruiting

Study Coordinator · Contact

540-982-0237

Fred Hutchinson Cancer Center ( Site 0069)

Seattle, Washington, 98109

Recruiting

Study Coordinator · Contact

855-557-0555

Cancer Care Northwest ( Site 0003)

Spokane, Washington, 99202

Recruiting

Study Coordinator · Contact

509-228-1000

Northwest Medical Specialties, PLLC ( Site 0067)

Tacoma, Washington, 98405

Recruiting

Study Coordinator · Contact

253-428-8700

University of Wisconsin-Madison ( Site 0024)

Madison, Wisconsin, 53792

Recruiting

Study Coordinator · Contact

608-263-0796