Clinical trial NCT05319730: 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)
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 Previously Exposed to PD-1/PD-L1 Treatment (KEYMAKER-U06): Substudy 06B
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Esophageal Squamous Cell Carcinoma
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: 2022-04-08
Enrollment: 200
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 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.

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

As of Protocol Amendment 5, the Pembrolizumab Plus MK-4830 Plus Paclitaxel/Irinotecan arm and the Pembrolizumab Plus MK-4830 Plus Lenvatinib arm are no longer actively enrolling participants.

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 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 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 history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
* Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention
* 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
* Participants with human immunodeficiency virus (HIV) with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Concurrent active hepatitis B and hepatitis C virus infection
* History of allogenic tissue/solid organ transplant
* Clinically significant cardiovascular disease within 12 months from first dose of study intervention
* Known gastrointestinal (GI) malabsorption or any other condition that may affect the absorption of lenvatinib. (Not applicable to actively enrolling arms as of Amendment 5)
* Has risk for significant 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. (Not applicable to actively enrolling arms as of Amendment 5)

Primary outcomes:
measure: Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) During Safety Lead-in Phase
timeFrame: Up to approximately 3 weeks
measure: Number of Participants Experiencing Adverse Events (AEs) 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 92 weeks
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Up to approximately 189 weeks
measure: Duration of Response (DOR)
timeFrame: Up to approximately 189 weeks
measure: Overall Survival (OS)
timeFrame: Up to approximately 189 weeks
measure: Number of Participants Experiencing at Least One Adverse Event (AE) During the Efficacy Phase
timeFrame: Up to approximately 189 weeks
measure: Number of Participants Who Discontinue Study Treatment Due to An AE During the Efficacy Phase
timeFrame: Up to approximately 189 weeks
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center-University of Arizona Cancer Center ( Site 4927)
state: Arizona
city: East Syracuse
country: United States
facility: Hematology-Oncology Associates of Central NY, P.C. ( Site 4925)
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center-CUIMC Herbert Irving Comprehensive Cancer Center Clinical ( Site 4907)
state: New York
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center-UPMC ( Site 4904)
state: Pennsylvania
city: Natal.
country: Brazil
facility: Liga Norte Riograndense Contra o Câncer ( Site 4303)
state: Rio Grande Do Norte
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceição ( Site 4301)
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 4300)
city: Santiago
country: Chile
facility: FALP-UIDO ( Site 4400)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Centro de Oncología de Precisión-Oncology ( Site 4404)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Clínica las Condes ( Site 4403)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Clínica UC San Carlos de Apoquindo ( Site 4405)
state: Region M. De Santiago
city: Hefei
country: China
facility: Anhui Provincial Hospital South District ( Site 3501)
state: Anhui
city: Beijing
country: China
facility: Beijing Cancer hospital-Digestive Oncology ( Site 3500)
state: Beijing
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xinxiang Medical University-Oncology ( Site 3510)
state: Henan
city: Huai'an
country: China
facility: First Huai'an Hospital Affiliated to Nanjing Medical University ( Site 3506)
state: Jiangsu
city: Shanghai
country: China
facility: Shanghai Chest Hospital-Esophageal surgery department ( Site 3513)
state: Shanghai
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital-Thoracic oncology ( Site 3511)
state: Zhejiang
city: Frankfurt
country: Germany
facility: Institut für Klinisch Onkologische Forschung-Klink für Onkologie und Hämatologie ( Site 4801)
state: Hessen
city: Düsseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf ( Site 4802)
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus Dresden-Medical Dept I - Medical Oncology ( Site 4806)
state: Sachsen
city: Berlin
country: Germany
facility: Charité Campus Virchow-Klinikum-Klinik Hämatologie Onkologie Tumorimmunologie ( Site 4804)
city: Meldola
country: Italy
facility: IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"-Oncologia Medica ( Site 3207)
state: Emilia-Romagna
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 3200)
state: Lombardia
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana ( Site 3206)
state: Toscana
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS-Oncologia Medica 1 ( Site 3203)
state: Veneto
city: Milano
country: Italy
facility: Ospedale San Raffaele-Oncologia Medica ( Site 3202)
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia IRCCS-Divisione di Sviluppo di Nuovi Farmaci per Terapie Innovative ( Site 3201)
city: Nagoya
country: Japan
facility: Aichi Cancer Center ( Site 3702)
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East ( Site 3701)
state: Chiba
city: Kitaadachi-gun
country: Japan
facility: Saitama Prefectural Cancer Center ( Site 3703)
state: Saitama
city: Nagaizumi-cho,Sunto-gun
country: Japan
facility: Shizuoka Cancer Center ( Site 3704)
state: Shizuoka
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital ( Site 3700)
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center-Department of Oncology ( Site 3901)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center-Division of Hematology/Oncology ( Site 3900)
city: Oslo
country: Norway
facility: Oslo universitetssykehus, Radiumhospitalet ( Site 4501)
city: Singapore
country: Singapore
facility: National University Hospital ( Site 3800)
state: South West
city: Genève
country: Switzerland
facility: Hôpitaux Universitaires de Genève (HUG) ( Site 4702)
state: Geneve
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden-Medizin ( Site 4700)
state: Grisons
city: Kaohsiung Niao Sung Dist
country: Taiwan
facility: Chang Gung Memorial Hospital at Kaohsiung ( Site 4003)
state: Kaohsiung
city: Taichung
country: Taiwan
facility: China Medical University Hospital ( Site 4007)
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital-Radiation Oncology ( Site 4008)
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital ( Site 4001)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital ( Site 4000)
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital ( Site 4005)
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation-Linkou Branch ( Site 4006)
city: Bangkok
country: Thailand
facility: Chulalongkorn University ( Site 4104)
state: Krung Thep Maha Nakhon
city: Bangkok
country: Thailand
facility: Faculty of Medicine Siriraj Hospital ( Site 4102)
state: Krung Thep Maha Nakhon
city: HatYai
country: Thailand
facility: Songklanagarind hospital ( Site 4105)
state: Songkhla
city: Adana
country: Turkey
facility: Adana Medical Park Seyhan Hastanesi-Medikal Onkoloji ( Site 3417)
city: Ankara
country: Turkey
facility: Hacettepe Universite Hastaneleri-oncology hospital ( Site 3402)
city: Ankara
country: Turkey
facility: Memorial Ankara Hastanesi-Medical Oncology ( Site 3408)
city: Ankara
country: Turkey
facility: Ankara Bilkent City Hospital-Medical Oncology ( Site 3405)
city: Erzurum
country: Turkey
facility: Atatürk Üniversitesi-onkoloji ( Site 3416)
city: Istanbul
country: Turkey
facility: TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 3403)
city: Izmir
country: Turkey
facility: I.E.U. Medical Point Hastanesi-Oncology ( Site 3406)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: