Clinical trial NCT05342636: A Study of Combination Therapies With or Without Pembrolizumab (MK-3475) and/or Chemotherapy in Participants With Advanced Esophageal Cancer (MK-3475-06A)
Official title: A Phase 1/2 Open-Label, Umbrella Platform Design Study of Investigational Agents With or Without Pembrolizumab (MK-3475) and/or Chemotherapy in Participants With Advanced Esophageal Cancer naïve to PD-1/PD-L1 Treatment (KEYMAKER-U06): Substudy 06A.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Esophageal Squamous Cell Carcinoma (ESCC)
Keywords: Esophageal cancer
Programmed Cell Death 1 (PD1, PD-1)
Programmed Cell Death 1 Ligand 1 (PDL-1, PD-L1)
Programmed Cell Death 1 Ligand 2 (PDL-2, PD-L2)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2022-04-22
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase I/II multicenter, open-label umbrella platform study that will evaluate the safety and efficacy of investigational agents with pembrolizumab, plus chemotherapy or lenvatinib, for the treatment of participants with advanced esophageal cancer who have failed 1 prior line of therapy and have not been previously exposed to programmed cell death 1 protein (PD-1)/ programmed cell death ligand 1 (PD-L1) based treatment.

With protocol amendment 5 (effective: 17-November-2023), enrollment in study arms "Pembrolizumab plus MK-4830 plus Chemotherapy" and "Pembrolizumab plus MK-4830 plus lenvatinib" is discontinued.

Detailed description: The master protocol is MK-3475-U06.

Eligibility criteria: The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

* Histologically or cytologically confirmed diagnosis of metastatic or locally advanced unresectable ESCC
* Has experienced investigator documented radiographic or clinical disease progression on one prior line of standard therapy.
* Has an evaluable baseline tumor sample (newly obtained or archival) for analysis
* Has adequately controlled blood pressure (BP) with or without antihypertensive medications
* 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 received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
* Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
* 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
* Active autoimmune disease that has required systemic treatment in past 2 years
* History of human immunodeficiency virus (HIV) infection
* History of Hepatitis B or known active Hepatitis C virus infection
* History of allogenic tissue/solid organ transplant
* Clinically significant cardiovascular disease within 12 months from first dose of study intervention
* Participants with known gastrointestinal (GI) malabsorption or any other condition that may affect the absorption of lenvatinib
* Has risk for significant GI bleeding, such as:
* Has had a serious nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to allocation/randomization
* Has significant bleeding disorders, vasculitis, or has had a significant bleeding episode from the GI tract within 12 weeks prior to allocation/randomization

Primary outcomes:
measure: Number of Participants Experiencing a Dose-limiting Toxicity (DLT) During Safety Lead-in Phase
timeFrame: Up to approximately 3 weeks
measure: Number of Participants Experiencing an Adverse Event (AE) During Safety Lead-in Phase
timeFrame: Up to approximately 3 Weeks
measure: Number of Participants Who Discontinue Study Treatment Due to an AE During Safety Lead-in Phase
timeFrame: Up to approximately 3 weeks
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 40 months
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Up to approximately 40 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 40 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 40 months
measure: Number of Participants Experiencing at Least One Adverse Event (AE) During the Efficacy Phase
timeFrame: Up to approximately 40 months
measure: Number of Participants Who Discontinue Study Treatment Due to An AE During the Efficacy Phase
timeFrame: Up to approximately 104 weeks
Other outcomes:
Locations:
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra o Câncer ( Site 2303)
state: Rio Grande Do Norte
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceição ( Site 2301)
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
facility: ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 2300)
state: Sao Paulo
city: Santiago
country: Chile
facility: FALP-UIDO ( Site 2400)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Clínica las Condes ( Site 2403)
state: Region M. De Santiago
city: Brest
country: France
facility: Centre Hospitalier Régional Universitaire de Brest - Hôpital Morvan ( Site 1104)
state: Finistere
city: Lille
country: France
facility: Hopital Claude Huriez - CHU de Lille ( Site 1100)
state: Nord
city: Paris
country: France
facility: Pitie Salpetriere University Hospital ( Site 1102)
state: Orne
city: Frankfurt
country: Germany
facility: Institut für Klinisch Onkologische Forschung-Klink für Onkologie und Hämatologie ( Site 2801)
state: Hessen
city: Düsseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf ( Site 2802)
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus Dresden-Medical Dept I - Medical Oncology ( Site 2806)
state: Sachsen
city: Berlin
country: Germany
facility: Charité Campus Virchow-Klinikum-Klinik Hämatologie Onkologie Tumorimmunologie ( Site 2804)
city: Milano
country: Italy
facility: Ospedale San Raffaele-Oncologia Medica ( Site 1206)
state: Lombardia
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 1200)
state: Lombardia
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia IRCCS-Divisione di Sviluppo di Nuovi Farmaci per Terapie Innovative (
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS ( Site 1205)
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital ( Site 1702)
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East ( Site 1701)
state: Chiba
city: Ina-machi
country: Japan
facility: Saitama Prefectural Cancer Center ( Site 1703)
state: Saitama
city: Nagaizumi-cho,Sunto-gun
country: Japan
facility: Shizuoka Cancer Center ( Site 1704)
state: Shizuoka
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital ( Site 1700)
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center-Department of Oncology ( Site 1901)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center-Division of Hematology/Oncology ( Site 1900)
city: Oslo
country: Norway
facility: Oslo universitetssykehus, Radiumhospitalet ( Site 2501)
city: Singapore
country: Singapore
facility: National University Hospital ( Site 1800)
state: South West
city: Genève
country: Switzerland
facility: Hôpitaux Universitaires de Genève (HUG) ( Site 2702)
state: Geneve
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden-Medizin ( Site 2700)
state: Grisons
city: Kaohsiung Niao Sung Dist
country: Taiwan
facility: Chang Gung Memorial Hospital at Kaohsiung ( Site 2003)
state: Kaohsiung
city: Taichung
country: Taiwan
facility: China Medical University Hospital ( Site 2007)
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital-Radiation Oncology ( Site 2008)
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital ( Site 2001)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital ( Site 2000)
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital ( Site 2005)
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation-Linkou Branch ( Site 2006)
city: Bangkok
country: Thailand
facility: Chulalongkorn University ( Site 2104)
state: Krung Thep Maha Nakhon
city: Bangkok
country: Thailand
facility: Faculty of Medicine Siriraj Hospital ( Site 2102)
state: Krung Thep Maha Nakhon
city: Hatyai
country: Thailand
facility: Songklanagarind hospital ( Site 2105)
state: Songkhla
city: Üsküdar / İstanbul
country: Turkey
facility: Acibadem Altunizade Hospital-Oncology ( Site 1407)
state: Istanbul
city: Izmir, Karsiyaka
country: Turkey
facility: I.E.U. Medical Point Hastanesi-Oncology ( Site 1406)
state: Izmir
city: Adana
country: Turkey
facility: Adana Medical Park Seyhan Hastanesi-Medikal Onkoloji ( Site 1417)
city: Ankara
country: Turkey
facility: Hacettepe Universite Hastaneleri-oncology hospital ( Site 1402)
city: Ankara
country: Turkey
facility: Memorial Ankara Hastanesi-Medical Oncology ( Site 1408)
city: Ankara
country: Turkey
facility: Ankara City Hospital-Medical Oncology ( Site 1405)
city: Antalya
country: Turkey
facility: Akdeniz Universitesi Hastanesi-Medical Oncology ( Site 1410)
city: Erzurum
country: Turkey
facility: Atatürk Üniversitesi-onkoloji ( Site 1416)
city: Istanbul
country: Turkey
facility: TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1403)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: