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

Merck Sharp & Dohme (MSD)

Status and phase: Enrolling; Phase 3

Conditions: Triple-Negative Breast Cancer

Treatments: Biological: sac-TMT; Biological: Pembrolizumab; Drug: Capecitabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT06393374

jRCT2031240476 (Registry Identifier)

2870-012

2023-504962-52 (Other Grant/Funding Number)

U1111-1289-8264 (Other Identifier)

Details and patient eligibility

About

This is a randomized, open-label study comparing the efficacy and safety of adjuvant sacituzumab tirumotecan (sac-TMT; 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 sac-TMT plus pembrolizumab to TPC (pembrolizumab or pembrolizumab plus capecitabine) with respect to invasive disease-free survival (iDFS) per investigator assessment. It is hypothesized that sac-TMT plus pembrolizumab is superior to TPC with respect to iDFS per investigator assessment.

Enrollment: 1,530 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 12 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 (100 days for MK-2870 and 95 days for capecitabine [no restriction for pembrolizumab]) AND 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 contraction after the last dose of study intervention (190 days for MK-2870, 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 Virus (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 corneal disease that prevents/delays corneal healing
• Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
• 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 (ADP 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 MK-2870 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, CTLA-4, OX-40, 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,530 participants in 2 patient groups

Pembrolizumab + sac-TMT

Experimental group

Description:

Participants receive pembrolizumab every 6 weeks (q6w) in combination with sac-TMT 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 sac-TMT infusions.

Treatment:

Biological: Pembrolizumab

Biological: sac-TMT

Treatment of Physician's Choice

Active Comparator group

Description:

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.

Treatment:

Drug: Capecitabine

Biological: Pembrolizumab