MK-2870-012

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

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Population: Breast - TNBC

Line of therapy: Adjuvant (Received Neoadjuvant Therapy and Did Not Achieve a Pathological Complete Response (pCR) at Surgery)

Intervention: MK-2870 (Sacituzumab Tirumotecan) in Combination with Pembrolizumab Versus Treatment of Physician’s Choice

Key Inclusion Criteria

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

2. Has no evidence of locoregional or distant relapse, as assessed by the treating physician

3. Had neoadjuvant treatment based on the KEYNOTE-522 regimen (pembrolizumab with carboplatin/taxanes and pembrolizumab with anthracycline-based chemotherapy) followed by surgery according to NCCN treatment guidelines for TNBC

4. Had adequate excision and surgical removal of all clinically evident disease in the breast and/or lymph nodes and have adequately recovered from surgery

5. Has non-pathologic complete response at surgery

6. Is able to continue on adjuvant pembrolizumab

7. Randomization must be conducted within 12 weeks from surgical resection

8. Completed adjuvant radiation therapy (if indicated) and recovered before randomization

9. Has provided tissue from the surgical resection for central laboratory determination of trophoblast cell surface antigen 2 (TROP2) status

10. Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline (except alopecia

11. Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on Antiretroviral Therapy (ART)

12. ECOG performance status of 0 to 1 assessed within 7 days before first dose of study treatment

13. 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

    
    

Key Exclusion Criteria

1. 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

2. Has Grade >2 peripheral neuropathy

3. History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing

4. Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease

5. Has uncontrolled, significant cardiovascular disease or cerebrovascular disease

6. Received prior treatment with a TROP2-directed ADC or a topoisomerase I inhibitor-containing ADC

7. 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

8. Is currently receiving a strong inducer/inhibitor of CYP3A4 that cannot be discontinued for the duration of the study. The required washout period before starting MK-2870 is 2 weeks

9. 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)

10. Except for chemotherapy as neoadjuvant therapy for early-stage TNBC: Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization

11. 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

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

13. 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

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

15. Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease

16. Has active infection requiring systemic therapy

17. HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease

18. Has concurrent active hepatitis B and hepatitis C virus infection

19. Has history of allogeneic tissue/solid organ transplant

Sponsor: Merck Sharp & Dohme LLC

CRP Contact:  herve.vennin.rendos.ccomtl@ssss.gouv.qc.ca

514-340-8222 ext. 27562

CRP PI: Dr. K. Martel

Status: Open to accrual