A Phase 1/2 Open-Label, Umbrella Platform Design of Investigational Agents With or Without Pembrolizumab (MK 3475) and/or Chemotherapy in Participants With Advanced Gastroesophageal Cancer: Master (KEYMAKER-U06)

The purpose of this study is studying MK-2870 in Esophageal Squamous Cell Carcinoma (ESCC). Each sub study in the larger clinical trial is different testing different trial drugs and/or drug combinations in people with advanced ESCC. • Sub study 06B is testing Chemotherapy and MK-2870. The chemotherapies that will be used in this sub study B are paclitaxel or irinotecan. • Sub study 06C will be testing Pembrolizumab plus chemo. The chemotherapies that will be used in substudy 06C are capecitabine, oxaliplatin, 5-fluorouracil (5- FU) plus leucovorin or levoleucovorin. The trial drugs/combination in this substudy being tested are pembrolizumab plus chemo and MK-2870 plus pembro plus chemo. • Sub study 06D is testing MK-2870 given with chemotherapy. The chemotherapies that will be in sub study 06D are ramucirumab and paclitaxel. The trial drugs/combination for this for this sub study being tested are Ramucirumab with paclitaxel and MK-2870 with paclitaxel.

Are you Eligible? (Inclusion Criteria)

• • at least 18 years of age • participant (or legally acceptable representative) willing to sign informed consent •Refrains from donating sperm PLUS either: • Abstains from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR • Uses contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview) as detailed below: - Uses a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penilevaginal penetration. - Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.