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

Inclusion Criteria:

• Has centrally confirmed TNBC, as defined by the most recent American Society ofClinical Oncology/College of American Pathologists (ASCO/CAP) guidelines

• Has no evidence of locoregional or distant relapse, as assessed by the treatingphysician

• Had neoadjuvant treatment based on the KEYNOTE-522 regimen (pembrolizumab withcarboplatin/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 thebreast 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 12 weeks from surgical resection

• Completed adjuvant radiation therapy (if indicated) and recovered beforerandomization

• Has provided tissue from the surgical resection for central laboratory determinationof trophoblast cell surface antigen 2 (TROP2) status

• If capable of producing sperm, the participant agrees to the following during theintervention period and for at least the time needed to eliminate each studyintervention after the last dose of study intervention (120 days for sacituzumabtirumotecan and 95 days for capecitabine [no restriction for pembrolizumab]): agreesto refrain from donating sperm AND is either abstinent and agrees to remainabstinent or uses highly effective contraception

• For females (assigned at birth), is not pregnant or breastfeeding and ≥1 of thefollowing applies: is not a participant of childbearing potential (POCBP) OR is aPOCBP and uses highly effective contraception after the last dose of studyintervention (210 days for sacituzumab tirumotecan, 120 days for pembrolizumab, and 185 days for capecitabine). Abstains from breastfeeding during the studyintervention period and for at least 120 days after study intervention

• Participants who have AEs due to previous anticancer therapies must have recoveredto ≤Grade 1 or baseline (except alopecia)

• Human immunodeficiency virus (HIV)-infected participants must have well controlledHIV on antiretroviral therapy (ART)

• An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessedwithin 7 days before first dose of study treatment

• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible ifthey 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 suspecteddeleterious) and is eligible for adjuvant therapy with olaparib where olaparib isapproved and available

• Has Grade >2 peripheral neuropathy

• History of documented severe dry eye syndrome, severe Meibomian gland disease and/orblepharitis, or corneal disease that prevents/delays corneal healing

• Has active inflammatory bowel disease requiring immunosuppressive medication orprevious history of inflammatory bowel disease (eg, Crohn's disease, ulcerativecolitis, or chronic diarrhea)

• Has uncontrolled, significant cardiovascular disease or cerebrovascular diseaseincluding 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 andcerebrovascular diseases within 6 months prior to study intervention

• Received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)-directedantibody drug conjugate (ADC) or a topoisomerase I inhibitor-containing ADC

• Received anticancer therapy in the adjuvant phase including but not limited tochemotherapy, small molecule anticancer drugs, poly (adenosine diphosphate ribose)polymerase (PARP) inhibitors, ADCs, and/or immunotherapy, with the exception ofadjuvant 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 washoutperiod before starting sacituzumab tirumotecan is 2 weeks

• Except for pembrolizumab as neoadjuvant therapy for early-stage TNBC: received priortherapy with an anti-programmed cell death 1 protein (anti-PD-1), anti-programmedcell death ligand 1 (anti-PD-L1), or anti-PD-L2 agent, or with an agent directed toanother stimulatory or coinhibitory T-cell receptor (eg, cytotoxicT-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 priorsystemic anticancer therapy including investigational agents within 4 weeks beforerandomization

• Received prior radiotherapy within 3 weeks of start of study intervention orrequired corticosteroids for radiation related toxicities that cannot bediscontinued before the first dose of study intervention

• Received a live or live-attenuated vaccine within 30 days before the first dose ofstudy intervention. Administration of killed vaccines are allowed

• Has received an investigational agent or has used an investigational device within 4weeks prior to study intervention administration

• Has known additional malignancy that is progressing or has required active treatmentwithin 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 ofimmunosuppressive therapy within 7 days prior the first dose of study medication

• Has active autoimmune disease that has required systemic treatment in the past 2years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid)is allowed

• Has history of (noninfectious) pneumonitis/interstitial lung disease that requiredsteroids 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 MulticentricCastleman's Disease

• Has concurrent active hepatitis B and hepatitis C virus infection

• Has history of allogeneic tissue/solid organ transplant