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Sacituzumab Tirumotecan (MK-2870) Plus Pembrolizumab Versus TPC in TNBC Who Did Not Achieve pCR (MK-2870-012)

RecruitingPhase 3

A Phase 3, Randomized, Open-label, Study to Compare the Efficacy and Safety of Adjuvant MK-2870 in Combination With Pembrolizumab (MK-3475) Versus Treatment of Physician's Choice (TPC) in Participants With Triple-Negative Breast Cancer (TNBC) Who Received Neoadjuvant Therapy and Did Not Achieve a Pathological Complete Response (pCR) at Surgery

Who can join

Ages 18 and older · All sexes

Full eligibility criteria
Inclusion Criteria:

* Has centrally confirmed TNBC, as defined by the most recent American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines
* Has no evidence of locoregional or distant relapse, as assessed by the treating physician
* Had neoadjuvant treatment based on the KEYNOTE-522 regimen (pembrolizumab with carboplatin/taxanes and pembrolizumab with anthracycline-based chemotherapy) followed by surgery according to National Comprehensive Cancer Network (NCCN) treatment guidelines for TNBC
* Had adequate excision and surgical removal of all clinically evident disease in the breast and/or lymph nodes and have adequately recovered from surgery
* Has non-pathologic complete response at surgery
* Is able to continue on adjuvant pembrolizumab
* Randomization must be conducted within 16 weeks from surgical resection
* Completed adjuvant radiation therapy (if indicated) and recovered before randomization
* Has provided tissue from the surgical resection for central laboratory determination of trophoblast cell surface antigen 2 (TROP2) status
* If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention (120 days for sacituzumab tirumotecan and 95 days for capecitabine \[no restriction for pembrolizumab\]): agrees to refrain from donating sperm AND is either abstinent and agrees to remain abstinent or uses highly effective contraception
* For females (assigned at birth), is not pregnant or breastfeeding and ≥1 of the following applies: is not a participant of childbearing potential (POCBP) OR is a POCBP and uses highly effective contraception after the last dose of study intervention (210 days for sacituzumab tirumotecan, 120 days for pembrolizumab, and 185 days for capecitabine). Abstains from breastfeeding during the study intervention period and for at least 120 days after study intervention
* Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline (except alopecia)
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
* An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before first dose of study treatment
* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B birus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to randomization

Exclusion Criteria:

* Has a known germline breast cancer gene (BRCA) mutation (deleterious or suspected deleterious) and is eligible for adjuvant therapy with olaparib where olaparib is approved and available
* Has Grade \>2 peripheral neuropathy
* 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 (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea)
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to \>480 ms, and/or other serious cardiovascular and cerebrovascular diseases within 6 months prior to study intervention
* Received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)-directed antibody drug conjugate (ADC) or a topoisomerase I inhibitor-containing ADC
* Received anticancer therapy in the adjuvant phase including but not limited to chemotherapy, small molecule anticancer drugs, poly (adenosine diphosphate ribose) polymerase (PARP) inhibitors, ADCs, and/or immunotherapy, with the exception of adjuvant radiation therapy
* Is currently receiving a strong inducer/inhibitor of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of the study. The required washout period before starting sacituzumab tirumotecan is 2 weeks
* Except for pembrolizumab as neoadjuvant therapy for early-stage TNBC: received prior therapy with an anti-programmed cell death 1 protein (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein-4 \[CTLA-4\], OX-40 \[cluster of differentiation (CD) 134\], or CD137)
* Except for chemotherapy as neoadjuvant therapy for early-stage TNBC: Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization
* Received prior radiotherapy within 3 weeks of start of study intervention or required corticosteroids for radiation related toxicities that cannot be discontinued before the first dose of study intervention
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed
* Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
* Has known additional malignancy that is progressing or has required active treatment within the past 5 years
* Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
* Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed
* Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has active infection requiring systemic therapy
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has concurrent active hepatitis B and hepatitis C virus infection
* Has history of allogeneic tissue/solid organ transplant

About the study

This is a randomized, open-label study comparing the efficacy and safety of adjuvant sacituzumab tirumotecan (MK-2870) in combination with pembrolizumab compared to treatment of physician's choice (TPC) in participants with triple-negative breast cancer (TNBC) who received neoadjuvant therapy and did not achieve a pathological complete response (pCR) at surgery. The primary objective is to compare sacituzumab tirumotecan plus pembrolizumab to TPC (pembrolizumab or pembrolizumab plus capecitabine) with respect to invasive disease-free survival (iDFS) per investigator assessment. It is hypothesized that sacituzumab tirumotecan plus pembrolizumab is superior to TPC with respect to iDFS per investigator assessment.

What is being tested

Sponsor: Merck Sharp & Dohme LLC · Participants: 1,530 · Started: Jun 24, 2024

Contact the study team

Official record on ClinicalTrials.gov — NCT06393374

Locations in the U.S.

AlabamaInfirmary Cancer Care ( Site 0001), Mobile
ArizonaIronwood Cancer & Research Centers-Research ( Site 0054), Chandler
CaliforniaMemorialCare Orange Coast Medical Center ( Site 9501), Fountain Valley
Scripps Cancer Center ( Site 0052), La Jolla
Kaiser Permanente - Oakland ( Site 0079), Oakland
Profound Research LLC ( Site 0105), Oceanside
Kaiser Permanente - Roseville ( Site 0081), Roseville
Kaiser Permanente - San Francisco ( Site 0080), San Francisco
Kaiser Permanente - Santa Clara ( Site 0082), Santa Clara
Providence Medical Foundation ( Site 9543), Santa Rosa
Kaiser Permanente Vallejo Medical Center ( Site 0060), Vallejo
Kaiser Permanente - Walnut Creek ( Site 0078), Walnut Creek
ColoradoCancer Centers of Colorado St. Mary's Regional Hospital ( Site 0046), Grand Junction
ConnecticutUniversity of Connecticut Health Center ( Site 0128), Farmington
Yale Cancer Center ( Site 0053), New Haven
DelawareHelen F. Graham Cancer Center & Research Institute ( Site 0018), Newark
FloridaAdventHealth Altamonte Springs ( Site 0125), Altamonte Springs
Orlando Health Cancer Institute ( Site 0030), Orlando
Comprehensive Hematology Oncology ( Site 0091), St. Petersburg
Cleveland Clinic Martin North Hospital ( Site 0114), Stuart
IllinoisIllinois Cancer Specialists (ICS) ( Site 8010), Arlington Heights
Southern Illinois Hospital Services ( Site 9547), Carterville
Orchard Healthcare Research Inc. ( Site 0014), Skokie
IndianaNorthwest Cancer Center - Dyer Clinic ( Site 0097), Dyer
Parkview Research Center at Parkview Regional Medical Center ( Site 0011), Fort Wayne
KentuckySaint Elizabeth Medical Center Edgewood-Cancer Care Center ( Site 0044), Edgewood
LouisianaCHRISTUS St. Frances Cabrini Hospital Center for Cancer Care ( Site 0109), Alexandria
Louisiana State University Health Sciences Shreveport ( Site 0029), Shreveport
MarylandHoly Cross Hospital ( Site 0069), Silver Spring
MichiganUniversity of Michigan ( Site 0103), Ann Arbor
Henry Ford Health ( Site 0010), Detroit
MinnesotaMetro-Minnesota Community Clinical Oncology ( Site 0031), Saint Louis Park
MississippiUniversity of Mississippi Medical Center ( Site 0043), Jackson
MissouriLake Regional Hospital ( Site 0009), Osage Beach
Siteman Cancer Center ( Site 0099), St Louis
NevadaComprehensive Cancer Centers of Nevada - Peak ( Site 0047), Las Vegas
Optum Care Cancer Center ( Site 9535), Las Vegas
New MexicoNew Mexico Oncology Hematology Consultants Ltd. ( Site 0090), Albuquerque
CHRISTUS St. Vincent Regional Cancer Center ( Site 0118), Santa Fe
New YorkIcahn School of Medicine at Mount Sinai ( Site 0123), New York
Memorial Sloan Kettering Cancer Center ( Site 0067), New York
The Blavatnik Family- Chelsea Medical Center at Mount Sinai ( Site 0135), New York
Clinical Research Alliance ( Site 0086), Westbury
North CarolinaLevine Cancer Institute ( Site 0083), Charlotte
Cape Fear Valley Health System ( Site 0136), Fayetteville
North DakotaSanford Cancer Center Bismarck ( Site 0058), Bismarck
Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 0056), Fargo
Altru Cancer Center ( Site 0104), Grand Forks
OhioCleveland Clinic - Mercy Hospital ( Site 0057), Canton
Tri-County Hematology & Oncology Associates, Inc. ( Site 0076), Massillon
Taylor Cancer Research Center ( Site 9500), Maumee
Genesis Healthcare System ( Site 0025), Zanesville
OklahomaOklahoma Cancer Specialists and Research Institute, LLC ( Site 0041), Tulsa
OregonProvidence Oncology and Hematology Care Clinic - Westside ( Site 0126), Portland
Providence Portland Medical Center ( Site 0116), Portland
PennsylvaniaSidney Kimmel Cancer Center at Jefferson ( Site 0049), Philadelphia
Cancer Care Associates Of York ( Site 9517), York
South DakotaSanford Cancer Center ( Site 0059), Sioux Falls
TennesseeWest Cancer Center and Research Institute ( Site 0084), Germantown
Baptist Cancer Center ( Site 0101), Memphis
One Oncology - Tennessee Oncology ( Site 0098), Nashville
SCRI Oncology Partners ( Site 7000), Nashville
Tennessee Oncology ( Site 0111), Nashville
Vanderbilt Health One Hundred Oaks ( Site 0042), Nashville
TexasHendrick Medical Center ( Site 0117), Abilene
Harrington Cancer Center ( Site 0061), Amarillo
Parkland Health & Hospital System ( Site 0096), Dallas
Texas Oncology - DFW ( Site 8000), Dallas
University of Texas Southwestern Medical Center ( Site 0032), Dallas
Texas Oncology - Northeast Texas ( Site 8005), Flower Mound
John Peter Smith Hospital ( Site 0106), Fort Worth
Oncology Consultants P.A. ( Site 0107), Houston
Laguna Clinical Research Associates LLC ( Site 0068), Laredo
Mays Cancer Center ( Site 0122), San Antonio
The University of Texas Health Science Center at Tyler dba UT Health East Texas HOPE Cancer Center ( Site 0055), Tyler
Texas Oncology - Gulf Coast ( Site 8009), Webster
UtahIntermountain Medical Center ( Site 0113), Murray
VirginiaHematology Oncology Associates of Fredericksburg ( Site 9550), Fredericksburg
Mary Washington Hospital ( Site 0129), Fredericksburg
Bon Secours Memorial Regional Medical Center-Oncology Research Department ( Site 0020), Midlothian
Virginia Oncology Associates (VOA) ( Site 8008), Norfolk
Virginia Cancer Institute ( Site 0034), Richmond
WashingtonNorthwest Medical Specialties, PLLC ( Site 0093), Tacoma
WisconsinSSM Health Dean Medical Group ( Site 0087), Madison

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.