Abstract 24TiP
Background
TROP2 expression is higher in TNBC vs other breast cancer subtypes, and high expression is associated with poor prognosis. Sac-TMT (MK-2870/SKB264) is a novel ADC composed of anti-TROP2 antibody coupled to a cytotoxic belotecan derivative via a novel linker (average drug/antibody ratio, 7.4). In a prior phase III study (OptiTROP-Breast01), sac-TMT alone improved PFS (HR, 0.31; 95% CI, 0.22-0.45; P < 0.00001) and OS (HR, 0.53; 95% CI, 0.36-0.78; P = 0.0005) vs chemotherapy (CTx) in patients (pts) with heavily pretreated advanced TNBC. The current standard of care (SOC) for pts with newly diagnosed, high-risk, early-stage TNBC is neoadjuvant pembrolizumab (pembro) + CTx followed by adjuvant pembro after surgery. Pts who do not achieve pCR with the current SOC have higher rates of recurrence and mortality vs pts who achieve pCR. This study (NCT06393374) evaluates adjuvant sac-TMT + pembro vs TPC (pembro ± capecitabine) in pts with TNBC who received neoadjuvant therapy and did not achieve pCR at surgery.
Trial design
This phase III, multicenter, open-label study is enrolling pts ≥18 y with centrally confirmed TNBC per most recent ASCO/CAP guidelines. Pts have non-pCR after ≥5 cycles of neoadjuvant pembro + CTx, including ≥1 cycle of anthracycline-based neoadjuvant therapy. Pts must provide tissue from the surgical specimen for central TROP2 assessment and be able to continue on adjuvant pembro. Randomization must be conducted ≤12 wks from surgical resection (window may be extended in consult with sponsor). Pts are randomized 1:1 to pembro 400 mg Q6W for 5 doses + sac-TMT 4 mg/kg Q2W for 12 doses or TPC with pembro 400 mg Q6W for 5 doses ± capecitabine 1000-1250 mg/m2 BID on D1-14 and D22-35 every 42 d for 4 cycles until completion of therapy or disease recurrence, unacceptable toxicity, or withdrawal. Randomization is stratified by residual tumor and lymph node status, TROP2 expression, and intention to use capecitabine. Primary endpoint is invasive disease-free survival. Secondary endpoints are OS, distant recurrence-free survival, PROs, and safety. Enrollment began Q2 2024.
Clinical trial identification
NCT06393374.
Legal entity responsible for the study
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Funding
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Disclosure
R.A. Dent: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis; Financial Interests, Personal, Advisory Board, Travel/Accommodation/Expenses: Eisai, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Pfizer, Roche. R. Hui: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, Eisai, Eli Lilly, Janssen, Merck & Co., Inc., Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Oncosec, Pfizer, Roche, Seagen, Takeda , Zai Lab; Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly, Janssen, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis; Financial Interests, Personal, Advisory Board, Research Support: AstraZeneca, BMS, Corvus, Eisai; Financial Interests, Personal, Advisory Board, Research Support to Organization: Eli Lilly, Janssen, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Oncosec, Roche, Seagen. Y.H. Park: Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, Novartis, Pfizer , Roche; Financial Interests, Personal, Research Funding: Alteogen, AstraZeneca, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Pfizer, Roche. P. Schmid: Financial Interests, Personal, Advisory Board, Consultant/Honoraria: AstraZeneca, Bayer, Boehringer Ingelheim, Celgene, Eisai, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Pfizer, Puma, Roche, Astellas; Financial Interests, Institutional, Research Grant: AstraZeneca, Genentech, Medivation, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Oncogenex, Roche. J. Wei, J.A. Mejia: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC; Financial Interests, Personal, Stocks/Shares: of Merck & Co., Inc. W. Pan: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA. J. Cortés: Financial Interests, Personal and Institutional, Research Funding, Research Grant: Roche; Financial Interests, Personal, Advisory Board, Travel/Accommodation/Expenses: Novartis, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Celgene, Lilly, Samsung Bioepis, Atenex, Biothera Pharmaceuticals, Cellestia, Erytech, Merus, Polyphor, Seattle Genetics, Servier; Financial Interests, Personal and Institutional, Research Funding, Research Grant, Travel/Accommodation/Expenses: Eisai, Pfizer; Financial Interests, Personal and Institutional, Advisory Board, Research grant/Funding: Merck Sharp & Dohme LLC, A subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Institutional, Advisory Board, Research grant/Funding: AstraZeneca; Financial Interests, Institutional, Research Funding, Research Grant: Ariad Pharmaceuticals, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Guardian Health, Piqur Therapeutics, Puma C, Queen Mary University of London, Seagen; Financial Interests, Personal, Stocks/Shares: MedSIR. H.L. McArthur: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Crown Bioscience, Daiichi Sankyo, Eli Lilly, Gilead, Pfizer, Puma, Seattle Genetics, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Advisory Board, Research Support: Bristol Myers Squibb, BTG, LLC/AstraZeneca, MedImmune, Merck Sharp & Dohme LLC, A subsidiary of Merck & Co., Inc., Rahway, NJ, USA.