Dysautonomia International

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

Purpose

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.

Condition

Triple-Negative Breast Cancer

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

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

Study Design

Phase: Phase 3
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Pembrolizumab + sacituzumab tirumotecan	Participants receive pembrolizumab every 6 weeks (q6w) in combination with sacituzumab tirumotecan every 2 weeks (q2w) for 24 weeks. In addition, participants receive an antihistamine, an H2 antagonist of investigator's choice, acetaminophen (or equivalent), and dexamethasone (or equivalent) per each drug's product label prior to sacituzumab tirumotecan infusions.	Biological: Pembrolizumab Pembrolizumab 400 mg intravenous (IV) infusion q6w Other names: KEYTRUDA® MK-3475 SCH 900475 Biological: Sacituzumab tirumotecan Sacituzumab tirumotecan 4 mg/kg IV infusion q2w Other names: MK-2870
Active Comparator Treatment of Physician's Choice	Participants receive pembrolizumab q6w or pembrolizumab q6w in combination with capecitabine (twice daily [BID] on Days 1 to 14 and 22 to 35 every 42 days x 4 [2 weeks 1, 1 week off]) for 24 weeks.	Biological: Pembrolizumab Pembrolizumab 400 mg intravenous (IV) infusion q6w Other names: KEYTRUDA® MK-3475 SCH 900475 Drug: Capecitabine Capecitabine 1000 mg/m^2 to 1250 mg/m^2 by mouth BID Other names: XELODA

Recruiting Locations

Infirmary Cancer Care ( Site 0001)
Mobile, Alabama 36607

Contact:
Study Coordinator
251-435-2273

Ironwood Cancer & Research Centers-Research ( Site 0054)
Chandler, Arizona 85224

Contact:
Study Coordinator
480-821-2838

MemorialCare Orange Coast Medical Center ( Site 9501)
Fountain Valley, California 92708

Contact:
Study Coordinator
714-378-7000

Scripps Cancer Center ( Site 0052)
La Jolla, California 92037

Contact:
Study Coordinator
800-727-4777

Kaiser Permanente - Oakland ( Site 0079)
Oakland, California 94611