Abstract 265TiP
Background
Patients with esophageal squamous cell carcinoma (ESCC) with disease progression after first-line chemotherapy with or without a PD-(L)1 inhibitor have limited treatment options and poor prognosis. The phase I/2 umbrella study KEYMAKER-U06 will be conducted to evaluate investigational agents with or without pembrolizumab and/or chemotherapy for advanced gastroesophageal cancer. Substudy 06B (NCT05319730) will be conducted to evaluate investigational agents with or without pembrolizumab and/or chemotherapy as second-line therapy for ESCC previously treated with a PD-(L)1 inhibitor.
Trial design
Patients aged ≥18 years with histologically or cytologically confirmed locally advanced unresectable or metastatic ESCC; disease progression on 1 prior line of platinum-based therapy and exposure to a PD-(L)1 inhibitor; measurable disease per RECIST v1.1 by blinded independent central review (BICR); and an Eastern Cooperative Oncology Group performance status of 0 or 1 will be eligible. Patients will be assigned to treatment arms 1 or 4: investigator’s choice of chemotherapy (paclitaxel 80-100 mg/m2 IV days 1, 8, and 15 of every 28-day cycle or irinotecan 180 mg/m2 day 1 of every 14-day cycle) (arm 1; ≥30 patients) or sacituzumab tirumotecan (also known as MK-2870/SKB264; trophoblast antigen 2–directed antibody drug conjugate) 4 mg/kg IV days 1, 15, and 29 of every 42-day cycle (arm 4; n ∼40 patients). Arms 2 (pembrolizumab 200 mg IV Q3W + MK-4830 800 mg IV Q3W + chemotherapy) and 3 (pembrolizumab + MK-4830 + lenvatinib 20 mg PO QD) are no longer enrolling. The primary end point is ORR per RECIST v1.1 by BICR in the efficacy phase (random assignment between arms 1 and 4); secondary end points are PFS and DOR per RECIST v1.1 by BICR, OS, safety, and tolerability. Enrollment is ongoing in arms 1 and 4.
Clinical trial identification
NCT05319730.
Legal entity responsible for the study
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and Eisai Inc, Nutley, NJ, USA.
Funding
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and Eisai Inc, Nutley, NJ, USA.
Disclosure
T. Doi: Financial Interests, Personal, Other, Advisory Role: Noil-Immune Biotech, Oncolys BioPharma, Boehringer Ingelheim, A2 Healthcare, PRA Health Sciences, KAKEN Pharma, Chugai Pharma, Sumitomo Pharma, Shionogi, Otsuka Pharma, Takeda, Kyowa Kirin, Rakuten Medical; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Taiho, MSD, AbbVie, Pfizer, BMS, Janssen Pharma, Daiichi Sankyo, Chugai Pharma, Boehringer Ingelheim, PRA Health Sciences, Amgen, GSK, Shionogi, RIN Institute, Ono Pharma, Bayer, Kyowa Kirin. P.C. Enzinger: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Role: Merck. M.A. Shah: Financial Interests, Institutional, Research Grant: Merck, Bristol Meyers Squibb, Oncolys Biopharma, Agenus; Non-Financial Interests, Institutional, Principal Investigator: Astellas. A. Adenis: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Principal Investigator: Novartis; Financial Interests, Personal and Institutional, Invited Speaker: BMS; Financial Interests, Personal and Institutional, Advisory Board: BMS, MSD; Financial Interests, Personal and Institutional, Principal Investigator: BMS, Bayer Pharma, MSD, AstraZeneca; Financial Interests, Personal and Institutional, Advisory Role: BMS, Bayer Pharma, Astra-Zeneca; Financial Interests, Personal and Institutional, Research Grant: Bayer Pharma, MSD; Financial Interests, Personal and Institutional, Other, Travel: Bayer Pharma, MSD, Astra-Zeneca; Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Personal, Other, Travel: Servier. J. Wu: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. K.P. Sharan, P. Bhagia: Financial Interests, Personal, Full or part-time Employment: Merck. K. Kato: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, Bristol Myers Squibb, Merck and Co; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical, Bristol Myers Squibb, Merck and Co, Bayer, AstraZeneca, Beigene, Taiho, Merck Biophrma, Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: Ono Pharmaceuticals, Merck & Co; Financial Interests, Institutional, Local PI: Bayer, AstraZeneca, Beigene, Taiho, Oncolys Biopharma, Merck Biopharma. L. Shen: Financial Interests, Personal, Advisory Board: MSD, BI, Servier, AZ, Transcenta Holding Limited; Financial Interests, Institutional, Funding: Beigene, Ltd.; Financial Interests, Institutional, Trial Chair: Rongchang Pharmaceutical, Roche, Innovent, Beigene, Ltd., NovaRock Biotherapeutics Limited. All other authors have declared no conflicts of interest.