NCT05319730Recruiting
A Study to Evaluate Investigational Agents With or Without Pembrolizumab (MK-3475) in Participants With Advanced Esophageal Cancer Previously Exposed to Programmed Cell Death 1 Protein (PD-1)/ Programmed Cell Death Ligand 1 (PD-L1) Treatment (MK-3475-06B)
Summary
This is a Phase 1/2, multicenter, randomized, open-label umbrella platform study to evaluate the safety and efficacy of investigational agents with or without pembrolizumab and/or chemotherapy, for the treatment of participants with second line (2L) esophageal squamous cell carcinoma (ESCC) who have previously been exposed to PD-1/PD-L1 based treatment.
Inclusion criteria
The main inclusion and exclusion criteria include but are not limited to the following: • Histologically or cytologically confirmed diagnosis of metastatic or locally advanced unresectable esophageal squamous cell carcinoma (ESCC) • Has experienced investigator documented radiographic or clinical disease progression on one prior line of standard therapy, that includes a platinum agent and previous exposure to an anti-programmed cell death 1 (PD1)/programmed cell death ligand 1 (PD-L1) based immune oncology (IO) therapy • Has provided an archival or most recent tumor tissue sample obtained as part of clinical practice • Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible
Exclusion criteria
• Direct invasion into adjacent organs such as the aorta or trachea • Has experienced weight loss \>10% over approximately 2 months prior to first dose of study therapy • Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing • Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease • Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration • Known additional malignancy that is progressing or has required active treatment within the past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that has undergone potentially curative therapy • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis • Participants with human immunodeficiency virus (HIV) with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease • History of allogenic tissue/solid organ transplant • Clinically significant cardiovascular disease within 12 months from first dose of study intervention • Has risk for significant gastrointestinal (GI) bleeding such as a serious nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to allocation/randomization, significant bleeding disorders, vasculitis, or has had a significant bleeding episode from the GI tract within 12 weeks prior to allocation/randomization
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, Germany, Italy, United States, Brazil, Chile, China, Japan, Norway, Singapore, South Korea, Taiwan, Thailand, Turkey (Türkiye)
- Sponsor
- Merck Sharp & Dohme LLC(Industry)
- Protocol no.
- 3475-06B
- Conditions
- Esophageal Squamous Cell Carcinoma
- Interventions
- Drug, Biological
Treatments studied
- Paclitaxel
- Irinotecan
- Pembrolizumab
- MK-4830
- Lenvatinib
- Sacituzumab tirumotecan
- Antihistamine
- H2 Receptor Antagonist
- Acetaminophen (or equivalent)
- Dexamethasone (or equivalent)
- Steroid Mouthwash (dexamethasone or equivalent)
- Supportive care measures
Locations · 48
- Geneva, SwitzerlandHôpitaux Universitaires de Genève (HUG) ( Site 4702)Recruiting at this site
- Chur, SwitzerlandKantonsspital Graubünden-Medizin ( Site 4700)Recruiting at this site
- Erdgeschoss, GermanyHOPE Hamburg/Norddeutsches Studienzentrum fuer Innovative Onkologie ( Site 4807)Recruiting at this site
- Meldola, ItalyIRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"-Oncologia Medica ( Site 3207)Recruiting at this site
- Milan, ItalyFondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 3200)Recruiting at this site
- Pisa, ItalyAzienda Ospedaliero Universitaria Pisana ( Site 3206)Recruiting at this site
- Padova, ItalyIstituto Oncologico Veneto IRCCS-Oncologia Medica 1 ( Site 3203)Recruiting at this site
- Milan, ItalyOspedale San Raffaele-Oncologia Medica ( Site 3202)Recruiting at this site
- Tucson, United StatesUniversity of Arizona Cancer Center-University of Arizona Cancer Center ( Site 4927)Recruiting at this site
- Los Angeles, United StatesUCLA Hematology/Oncology - Santa Monica ( Site 4905)Recruiting at this site
- East Syracuse, United StatesHematology-Oncology Associates of Central NY, P.C. ( Site 4925)Recruiting at this site
- Pittsburgh, United StatesUPMC Hillman Cancer Center-UPMC ( Site 4904)Recruiting at this site
- Natal, BrazilLiga Norte Riograndense Contra o Câncer ( Site 4303)Recruiting at this site
- Porto Alegre, BrazilHospital Nossa Senhora da Conceição ( Site 4301)Recruiting at this site
- São Paulo, BrazilICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 4300)Recruiting at this site
- Santiago, ChileFALP-UIDO ( Site 4400)Recruiting at this site
- Santiago, ChileCentro de Oncología de Precisión-Oncology ( Site 4404)Recruiting at this site
- Santiago, ChileClínica UC San Carlos de Apoquindo ( Site 4405)Recruiting at this site
- Hefei, ChinaAnhui Provincial Hospital ( Site 3501)Recruiting at this site
- Beijing, ChinaBeijing Cancer hospital-Digestive Oncology ( Site 3500)Recruiting at this site
- Xiamen, ChinaThe First Affiliated Hospital of Xiamen University ( Site 3516)Recruiting at this site
- Xinxiang, ChinaThe First Affiliated Hospital of Xinxiang Medical University-Oncology ( Site 3510)Recruiting at this site
- Zhengzhou, ChinaHenan Cancer Hospital ( Site 3518)Recruiting at this site
- Huai'an, ChinaFirst Huai'an Hospital Affiliated to Nanjing Medical University ( Site 3506)Recruiting at this site
- Shanghai, ChinaShanghai Chest Hospital-Esophageal surgery department ( Site 3513)Recruiting at this site
- Hangzhou, ChinaZhejiang Cancer Hospital-Thoracic oncology ( Site 3511)Recruiting at this site
- Nagoya, JapanAichi Cancer Center ( Site 3702)Recruiting at this site
- Kashiwa, JapanNational Cancer Center Hospital East ( Site 3701)Recruiting at this site
- Kitaadachi-gun, JapanSaitama Prefectural Cancer Center ( Site 3703)Recruiting at this site
- Nagaizumi-cho,Sunto-gun, JapanShizuoka Cancer Center ( Site 3704)Recruiting at this site
In total, worldwide, 48 of the 58 sites listed in the registry are recruiting; the other 10 are not currently recruiting.
Site status per the ClinicalTrials.gov registry (last update posted: October 7, 2026).
This status may have changed and says nothing about your eligibility: before taking any step, check with your oncologist or the site.
+ 18 more locations
Other identifiers
- jRCT2031220582 · other registry
- 2023-505189-26-00 · other registry
- U1111-1291-1987 · other registry
- MK-3475-06B · other identifier
- KEYMAKER-U06B · other identifier
- 2021-005443-76 · EudraCT number
- 2023 · NIH grant
See also
Other versions
These results are indicative and do not replace medical advice — discuss them with your doctor.