NCT06780111Recruiting
Substudy 06E: Umbrella Study of Combination Therapies in Esophageal Cancer (MK-3475-06E/KEYMAKER-U06)
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.
Inclusion criteria
The main inclusion criteria include but are not limited to the following: • Has histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic squamous cell carcinoma of the esophagus in first-line (1L) setting. • Has measurable disease per RECIST 1.1 as assessed by the local site. investigator or designee/radiology assessment and verified by BICR. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions. • Has had AEs due to previous anticancer therapies that have recovered to ≤Grade 1 or baseline. Endocrine-related AEs that are adequately treated with hormone replacement are elegible. • Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART). • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. • Has adequate organ function.
Exclusion criteria
The main exclusion criteria include but are not limited to the following: • Has had systemic anticancer therapy for locally advanced unresectable or metastatic esophageal cancer. • Has tumor invasion into organs located adjacent to the esophageal disease site (eg, aorta or respiratory tract) at an increased risk of fistula. • Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention. • Has clinically significant corneal disease, history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing. • HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease. • Has received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti-programmed cell death ligand 2 (PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor. • Has received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention. • Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids. • Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed. • Has inadequate cardiac function assessed as by a corrected QT interval by Fredericia (QTcF) value ≥470 msec. • Has clinically significant cardiovascular disease within 6 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. • Has peripheral neuropathy ≥ Grade 2. • 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 to the first dose of study intervention. • Has known additional malignancy that is progressing or has required active treatment within the past 3 years. • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. • Has active autoimmune disease that has required systemic treatment in the past 2 years. • Has had a history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use (except for a history of radiation pneumonitis that did not require steroids), has a current diagnosis of ILD, or has clinical or radiographic suspicion of ILD for which the diagnosis of ILD cannot be ruled out. • Has active infection requiring systemic therapy. • Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder.
Contacts
The trial team's contact details are shown on request.
See the official trial record- Status
- Recruiting
- Phase
- Phase 1 · Phase 2
- Study type
- Interventional
- Countries
- Switzerland, France, Germany, Italy, United States, Brazil, Chile, China, Czechia, Japan, Norway, Singapore, South Korea, Taiwan, Thailand, Turkey (Türkiye)
- Sponsor
- Merck Sharp & Dohme LLC(Industry)
- Protocol no.
- 3475-06E
- Conditions
- Esophageal Squamous Cell Carcinoma
- Interventions
- Biological, Drug
Treatments studied
- Pembrolizumab
- I-DXd
- Leucovorin
- Levoleucovorin
- 5-Fluorouracil (5-FU)
- Oxaliplatin
- Sacituzumab tirumotecan
- Rescue Medication
Collaborators
Daiichi Sankyo
Locations · 52
- Chur, SwitzerlandKantonsspital Graubuenden ( Site 1700)Recruiting at this site
- Geneva, SwitzerlandHopitaux Universitaires de Geneve HUG. ( Site 1701)Recruiting at this site
- Brest, FranceC.H.R.U. de Brest - Hopital Cavale Blanche ( Site 9104)Recruiting at this site
- Lille, FranceCHU Lille - Institut Coeur Poumon ( Site 9100)Recruiting at this site
- Paris, FrancePitie Salpetriere University Hospital ( Site 9102)Recruiting at this site
- Heidelberg, GermanyNCT-Department of Medical Oncology ( Site 1809)Recruiting at this site
- Erdgeschoss, GermanyHOPE Hamburg/Norddeutsches Studienzentrum fuer Innovative Onkologie ( Site 1807)Recruiting at this site
- Düsseldorf, GermanyUniversitaetsklinikum Duesseldorf ( Site 1808)Recruiting at this site
- Dresden, GermanyUniversitätsklinikum Carl Gustav Carus - Medical Oncology ( Site 1806)Recruiting at this site
- Milan, ItalyOspedale San Raffaele-Oncologia Medica ( Site 9201)Recruiting at this site
- Padova, ItalyIstituto Oncologico Veneto IRCCS ( Site 9202)Recruiting at this site
- Pittsburgh, United StatesUPMC Hillman Cancer Center ( Site 1904)Recruiting at this site
- Natal, BrazilLiga Norte Riograndense Contra o Cancer ( Site 1301)Recruiting at this site
- Porto Alegre, BrazilHospital Nossa Senhora da Conceicao ( Site 1300)Recruiting at this site
- São Paulo, BrazilIBCC - Instituto Brasileiro de Controle do Cancer ( Site 1303)Recruiting at this site
- São Paulo, BrazilICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 1302)Recruiting at this site
- Port Montt, ChileClínica Puerto Montt ( Site 1406)Recruiting at this site
- Santiago, ChileFundación Arturo López Pérez ( Site 1400)Recruiting at this site
- Santiago, ChileCentro de Oncología de Precisión ( Site 1402)Recruiting at this site
- Santiago, ChileClínica UC San Carlos de Apoquindo ( Site 1403)Recruiting at this site
- Santiago, ChileBradfordhill ( Site 1401)Recruiting at this site
- Antofagasta, ChileBradford Hill Norte ( Site 1405)Recruiting at this site
- Hefei, ChinaThe Second Affiliated Hospital of Anhui Medical University ( Site 9511)Recruiting at this site
- Beijing, ChinaBeijing Cancer Hospital ( Site 9500)Recruiting at this site
- Xiamen, ChinaThe First Affiliated Hospital of Xiamen University ( Site 9503)Recruiting at this site
- Zhengzhou, ChinaHenan Cancer Hospital ( Site 9509)Recruiting at this site
- Xuzhou, ChinaXuzhou Central Hospital ( Site 9512)Recruiting at this site
- Nanchang, ChinaThe First Affiliated Hospital of Nanchang University ( Site 9505)Recruiting at this site
- Brno, CzechiaMasarykuv onkologicky ustav-Klinika komplexni onkologicke pece ( Site 9000)Recruiting at this site
- Nagoya, JapanAichi Cancer Center ( Site 9702)Recruiting at this site
In total, worldwide, all 52 sites listed in the registry are recruiting.
Site status per the ClinicalTrials.gov registry (last update posted: October 27, 2026).
This status may have changed and says nothing about your eligibility: before taking any step, check with your oncologist or the site.
+ 22 more locations
Other identifiers
- MK-3475-06E · other identifier
- 2024-514273-22-00 · other registry
- U1111-1307-6484 · other registry
- jRCT2041240166 · other registry
See also
Other versions
These results are indicative and do not replace medical advice — discuss them with your doctor.