Clinical trial NCT06780111: Substudy 06E: Umbrella Study of Combination Therapies in Esophageal Cancer (MK-3475-06E/KEYMAKER-U06)
Official title: A Phase 1/2 Open-Label, Umbrella Platform Design Study of Investigational Agents in Combination With Pembrolizumab (MK-3475) With or Without Chemotherapy in Participants With 1L Locally Advanced Unresectable/Metastatic Esophageal Cancer: KEYMAKER-U06 Substudy 06E
Conditions: Esophageal Squamous Cell Carcinoma
Summary: Researchers are looking for new ways to treat esophageal squamous cell carcinoma (ESCC). ESCC is a type of cancer that starts in certain cells that line the esophagus. The esophagus is the tube that connects the throat to the stomach. This study will look at ESCC that is either locally advanced unresectable, which means it has spread into tissue near where it started and cannot be completely removed by surgery, or metastatic, which means it has spread to other body parts.
Available treatments for these types of ESCC include pembrolizumab and chemotherapy. Pembrolizumab is an immunotherapy, which is a treatment that helps the immune system fight cancer. Chemotherapy is medicine that destroys cancer cells or stops them from growing.
Researchers want to learn about giving pembrolizumab and investigational agents, with or without chemotherapy to treat ESCC. Ifinatamab deruxtecan (I-DXd), is an antibody-drug conjugate (ADC). An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells.
The main goal of this study is to learn about the safety of investigational agents and pembrolizumab with or without chemotherapy and if people tolerate them. Researchers also want to learn how cancer responds (gets smaller or goes away) to the study treatments.
Interventions:
description: IV infusion
name: Pembrolizumab
other_name: KEYTRUDA®
MK-3475
type: Biological
description: IV infusion
name: I-DXd
other_name: DS-7300a
Ifinatamab deruxtecan
MK-2400
type: Biological
description: IV infusion
name: Leucovorin
type: Drug
description: IV infusion
name: Levoleucovorin
type: Drug
description: IV Infusion
name: 5-Fluorouracil (5-FU)
type: Drug
description: IV infusion
name: Oxaliplatin
type: Drug
description: IV infusion
name: Sacituzumab tirumotecan
other_name: MK-2870
SKB264
type: Biological
description: Includes 5-HT3 receptor antagonist, NK-1 receptor antagonist, and corticosteroid for Arms 2, 3, and 4, and H1 receptor antagonist, H2 receptor antagonist, acetaminophen, and dexamethasone for Arm 5, administered per approved product label
name: Rescue Medication
type: Drug
Study arms:
design_group_description: Participants will receive 400 mg of pembrolizumab via intravenous (IV) infusion every six weeks (Q6W) on Day 1 of each 42 day cycle up to 18 cycles (up to approximately 2 years), and mFOLFOX6 chemotherapy: oxaliplatin 85 mg/m^2 via IV infusion every 2 weeks (Q2W) until progressive disease (PD) or toxicity; leucovorin 400 mg/m2 OR levoleucovorin 200 mg/m^2 via IV infusion Q2W until PD or toxicity; 5-fluorouracil (5-FU) 400 mg/m^2 bolus IV infusion followed by 2400 mg/m^2 continuous 46-48 hour IV infusion Q2W until PD or toxicity.
design_group_title: Pembrolizumab + Chemotherapy
design_group_type: Active Comparator
design_group_description: Participants will receive 200 mg of pembrolizumab via IV infusion Q3W on Day 1 of each 21 day cycle for up to 35 cycles (up to approximately 2 years). Participants will also receive up to 12 mg/kg I-XDd Q3W via IV infusion until PD or toxicity.
design_group_title: Pembrolizumab + I-DXd
design_group_type: Experimental
design_group_description: Participants will receive 200 mg pembrolizumab via IV infusion Q3W on Day 1 of each 21 day cycle up to 35 cycles (up to approximately 2 years). Participants will also receive I-DXd up to 12 mg/kg via IV infusion Q3W until PD or toxicity, 5-FU 400 mg/m^2 bolus IV infusion followed by 2400 mg/m^2 continuous 46-48 hour IV infusion Q2W until PD or toxicity, and leucovorin 400 mg/m^2 OR levoleucovorin 200 mg/m^2 via IV infusion Q2W until PD or toxicity.
design_group_title: Pembrolizumab + I-DXd + 5-FU IV + Leucovorin or Levoleucovorin
design_group_type: Experimental
design_group_description: Participants will receive 200 mg of pembrolizumab via IV infusion Q3W on Day 1 of each 21 day cycle up to 35 cycles (up to approximately 2 years). Participants will also receive up to 12 mg/kg I-DXd via IV infusion q3w until PD or toxicity, 5-FU 2400 mg/m^2 continuous 46-48 hour IV infusion Q2W until PD or toxicity, 60mg/m^2 oxaliplatin via IV infusion Q2W until PD or toxicity, and leucovorin 400 mg/m^2 OR levoleucovorin 200 mg/m^2 via IV infusion Q2W until PD or toxicity.
design_group_title: Pembrolizumab + I-DXd + 5-FU IV + Leucovorin or Levoleucovorin + Oxaliplatin
design_group_type: Experimental
design_group_description: Participants will receive 400 mg pembrolizumab via IV infusion Q6W on Day 1 of each 42 day cycle up to 18 cycles (up to approximately 2 years). Participants will also receive sacituzumab tirumotecan 4 mg/kg via IV infusion Days 1, 15, and 29 every 42 day cycle until PD or toxicity, 5-FU 400 mg/m^2 bolus IV infusion followed by 2400 mg/m^2 continuous 46-48 hour IV infusion Q2W until PD or toxicity, and leucovorin 400 mg/m^2 OR levoleucovorin 200 mg/m^2 via IV infusion Q2W until PD or toxicity.
design_group_title: Pembrolizumab + Sacituzumab tirumotecan + 5-FU IV + Leucovorin or Levoleucovorin
design_group_type: Experimental
Sponsor: Merck Sharp & Dohme LLC
Collaborators: Daiichi Sankyo Co., Ltd.
Drug name mappings:
name: 亚叶酸钙
lang: CN
name: Leucovorin Calcium
lang: EN
name: ホリナートカルシウム
lang: JP
name: Ifinatamab deruxtecan
lang: EN
name: イフィナタマブ デルクステカン（遺伝子組換え）
lang: JP
name: 帕博利珠单抗
lang: CN
name: Pembrolizumab
lang: EN
name: ペムブロリズマブ（遺伝子組換え）
lang: JP
name: 芦康沙妥珠单抗
lang: CN
name: Sacituzumab tirumotecan
lang: EN
name: 左亚叶酸
lang: CN
name: Levoleucovorin
lang: EN
name: 奥沙利铂
lang: CN
name: Oxaliplatin
lang: EN
name: オキサリプラチン
lang: JP
name: 氟尿嘧啶
lang: CN
name: Fluorouracil
lang: EN
name: フルオロウラシル
lang: JP