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)
- Conditions
- Esophageal Squamous Cell Carcinoma
- Interventions
- Drug: AntihistamineDrug: H2 Receptor AntagonistDrug: Steroid Mouthwash (dexamethasone or equivalent)Drug: Supportive care measures
- Registration Number
- NCT05319730
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 200
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Paclitaxel or irinotecan Paclitaxel Participants receive paclitaxel 80-100 mg/m\^2 intravenously (IV) on days 1, 8, and 15 every 28-day cycle until progressive disease (PD) or discontinuation, or irinotecan 180 mg/m\^2 IV on day 1 of every 14-day cycle until PD or discontinuation. Paclitaxel or irinotecan Irinotecan Participants receive paclitaxel 80-100 mg/m\^2 intravenously (IV) on days 1, 8, and 15 every 28-day cycle until progressive disease (PD) or discontinuation, or irinotecan 180 mg/m\^2 IV on day 1 of every 14-day cycle until PD or discontinuation. Pembrolizumab + MK-4830 + paclitaxel or irinotecan Paclitaxel Participants receive pembrolizumab 200 mg IV once every 3 weeks (Q3W) for up to 35 cycles (cycle=21 days) or until PD or discontinuation + MK-4830 800 mg IV Q3W up to 35 infusions + paclitaxel 80-100 mg/m\^2 IV on days 1, 8, and 15 every 28-day cycle until PD or discontinuation or irinotecan 180 mg/m\^2 180 mg/m\^2 on day 1 every 14-day cycle until PD or discontinuation. Pembrolizumab + MK-4830 + paclitaxel or irinotecan Irinotecan Participants receive pembrolizumab 200 mg IV once every 3 weeks (Q3W) for up to 35 cycles (cycle=21 days) or until PD or discontinuation + MK-4830 800 mg IV Q3W up to 35 infusions + paclitaxel 80-100 mg/m\^2 IV on days 1, 8, and 15 every 28-day cycle until PD or discontinuation or irinotecan 180 mg/m\^2 180 mg/m\^2 on day 1 every 14-day cycle until PD or discontinuation. Pembrolizumab + MK-4830 + paclitaxel or irinotecan Pembrolizumab Participants receive pembrolizumab 200 mg IV once every 3 weeks (Q3W) for up to 35 cycles (cycle=21 days) or until PD or discontinuation + MK-4830 800 mg IV Q3W up to 35 infusions + paclitaxel 80-100 mg/m\^2 IV on days 1, 8, and 15 every 28-day cycle until PD or discontinuation or irinotecan 180 mg/m\^2 180 mg/m\^2 on day 1 every 14-day cycle until PD or discontinuation. Pembrolizumab + MK-4830 + paclitaxel or irinotecan MK-4830 Participants receive pembrolizumab 200 mg IV once every 3 weeks (Q3W) for up to 35 cycles (cycle=21 days) or until PD or discontinuation + MK-4830 800 mg IV Q3W up to 35 infusions + paclitaxel 80-100 mg/m\^2 IV on days 1, 8, and 15 every 28-day cycle until PD or discontinuation or irinotecan 180 mg/m\^2 180 mg/m\^2 on day 1 every 14-day cycle until PD or discontinuation. Pembrolizumab + MK-4830 + lenvatinib Pembrolizumab Participants receive pembrolizumab 200 mg IV Q3W up to 35 cycles (cycle=21 days) until PD or discontinuation + MK-4830 800 mg IV Q3W up to 35 infusions + lenvatinib 20 mg oral administration every day until PD or discontinuation. Pembrolizumab + MK-4830 + lenvatinib MK-4830 Participants receive pembrolizumab 200 mg IV Q3W up to 35 cycles (cycle=21 days) until PD or discontinuation + MK-4830 800 mg IV Q3W up to 35 infusions + lenvatinib 20 mg oral administration every day until PD or discontinuation. Pembrolizumab + MK-4830 + lenvatinib Lenvatinib Participants receive pembrolizumab 200 mg IV Q3W up to 35 cycles (cycle=21 days) until PD or discontinuation + MK-4830 800 mg IV Q3W up to 35 infusions + lenvatinib 20 mg oral administration every day until PD or discontinuation. Sacituzumab tirumotecan Sacituzumab tirumotecan Participants will receive 4 mg/kg of sacituzumab tirumotecan via IV infusion on Days 1, 15, and 29 of each 42-day cycle until discontinuation. Sacituzumab tirumotecan Antihistamine Participants will receive 4 mg/kg of sacituzumab tirumotecan via IV infusion on Days 1, 15, and 29 of each 42-day cycle until discontinuation. Sacituzumab tirumotecan H2 Receptor Antagonist Participants will receive 4 mg/kg of sacituzumab tirumotecan via IV infusion on Days 1, 15, and 29 of each 42-day cycle until discontinuation. Sacituzumab tirumotecan Acetaminophen (or equivalent) Participants will receive 4 mg/kg of sacituzumab tirumotecan via IV infusion on Days 1, 15, and 29 of each 42-day cycle until discontinuation. Sacituzumab tirumotecan Dexamethasone (or equivalent) Participants will receive 4 mg/kg of sacituzumab tirumotecan via IV infusion on Days 1, 15, and 29 of each 42-day cycle until discontinuation. Sacituzumab tirumotecan Steroid Mouthwash (dexamethasone or equivalent) Participants will receive 4 mg/kg of sacituzumab tirumotecan via IV infusion on Days 1, 15, and 29 of each 42-day cycle until discontinuation. Sacituzumab tirumotecan Supportive care measures Participants will receive 4 mg/kg of sacituzumab tirumotecan via IV infusion on Days 1, 15, and 29 of each 42-day cycle until discontinuation.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) Up to approximately 92 weeks ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.
Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) During Safety Lead-in Phase Up to approximately 3 weeks A DLT is defined as any drug-related AE according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) Version 5.0, observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next cycle.
Number of Participants Experiencing Adverse Events (AEs) During Safety Lead-in Phase Up to approximately 3 weeks An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Number of Participants Who Discontinue Study Treatment Due to an AE During Safety Lead-in Phase Up to approximately 3 weeks An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be presented.
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Up to approximately 189 weeks PFS is defined as the time from allocation to the first documented progressive disease (PD) as assessed by RECIST 1.1 or death due to any cause, whichever occurs first. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented.
Duration of Response (DOR) Up to approximately 189 weeks For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented.
Number of Participants Experiencing at Least One Adverse Event (AE) During the Efficacy Phase Up to approximately 189 weeks An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Number of Participants Who Discontinue Study Treatment Due to An AE During the Efficacy Phase Up to approximately 189 weeks An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Overall Survival (OS) Up to approximately 189 weeks OS is defined as the time from the date of allocation to death from any cause.
Trial Locations
- Locations (55)
Columbia University Irving Medical Center-CUIMC Herbert Irving Comprehensive Cancer Center Clinical ( Site 4907)
🇺🇸New York, New York, United States
IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"-Oncologia Medica ( Site 3207)
🇮🇹Meldola, Emilia-Romagna, Italy
Istituto Europeo di Oncologia IRCCS-Divisione di Sviluppo di Nuovi Farmaci per Terapie Innovative ( Site 3201)
🇮🇹Milano, Italy
University of Arizona Cancer Center-University of Arizona Cancer Center ( Site 4927)
🇺🇸Tucson, Arizona, United States
Hematology-Oncology Associates of Central NY, P.C. ( Site 4925)
🇺🇸East Syracuse, New York, United States
UPMC Hillman Cancer Center-UPMC ( Site 4904)
🇺🇸Pittsburgh, Pennsylvania, United States
Liga Norte Riograndense Contra o Câncer ( Site 4303)
🇧🇷Natal., Rio Grande Do Norte, Brazil
Hospital Nossa Senhora da Conceição ( Site 4301)
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 4300)
🇧🇷Sao Paulo, Brazil
FALP-UIDO ( Site 4400)
🇨🇱Santiago, Region M. De Santiago, Chile
Centro de Oncología de Precisión-Oncology ( Site 4404)
🇨🇱Santiago, Region M. De Santiago, Chile
Clínica las Condes ( Site 4403)
🇨🇱Santiago, Region M. De Santiago, Chile
Clínica UC San Carlos de Apoquindo ( Site 4405)
🇨🇱Santiago, Region M. De Santiago, Chile
Anhui Provincial Hospital South District ( Site 3501)
🇨🇳Hefei, Anhui, China
Beijing Cancer hospital-Digestive Oncology ( Site 3500)
🇨🇳Beijing, Beijing, China
The First Affiliated Hospital of Xinxiang Medical University-Oncology ( Site 3510)
🇨🇳Xinxiang, Henan, China
First Huai'an Hospital Affiliated to Nanjing Medical University ( Site 3506)
🇨🇳Huai'an, Jiangsu, China
Shanghai Chest Hospital-Esophageal surgery department ( Site 3513)
🇨🇳Shanghai, Shanghai, China
Zhejiang Cancer Hospital-Thoracic oncology ( Site 3511)
🇨🇳Hangzhou, Zhejiang, China
Institut für Klinisch Onkologische Forschung-Klink für Onkologie und Hämatologie ( Site 4801)
🇩🇪Frankfurt, Hessen, Germany
Universitaetsklinikum Duesseldorf ( Site 4802)
🇩🇪Düsseldorf, Nordrhein-Westfalen, Germany
Universitaetsklinikum Carl Gustav Carus Dresden-Medical Dept I - Medical Oncology ( Site 4806)
🇩🇪Dresden, Sachsen, Germany
Charité Campus Virchow-Klinikum-Klinik Hämatologie Onkologie Tumorimmunologie ( Site 4804)
🇩🇪Berlin, Germany
Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 3200)
🇮🇹Milan, Lombardia, Italy
Azienda Ospedaliero Universitaria Pisana ( Site 3206)
🇮🇹Pisa, Toscana, Italy
Istituto Oncologico Veneto IRCCS-Oncologia Medica 1 ( Site 3203)
🇮🇹Padova, Veneto, Italy
Ospedale San Raffaele-Oncologia Medica ( Site 3202)
🇮🇹Milano, Italy
Aichi Cancer Center ( Site 3702)
🇯🇵Nagoya, Aichi, Japan
National Cancer Center Hospital East ( Site 3701)
🇯🇵Kashiwa, Chiba, Japan
Saitama Prefectural Cancer Center ( Site 3703)
🇯🇵Kitaadachi-gun, Saitama, Japan
Shizuoka Cancer Center ( Site 3704)
🇯🇵Nagaizumi-cho,Sunto-gun, Shizuoka, Japan
National Cancer Center Hospital ( Site 3700)
🇯🇵Chuo-ku, Tokyo, Japan
Asan Medical Center-Department of Oncology ( Site 3901)
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center-Division of Hematology/Oncology ( Site 3900)
🇰🇷Seoul, Korea, Republic of
Oslo universitetssykehus, Radiumhospitalet ( Site 4501)
🇳🇴Oslo, Norway
National University Hospital ( Site 3800)
🇸🇬Singapore, South West, Singapore
Hôpitaux Universitaires de Genève (HUG) ( Site 4702)
🇨🇭Genève, Geneve, Switzerland
Kantonsspital Graubünden-Medizin ( Site 4700)
🇨🇭Chur, Grisons, Switzerland
Chang Gung Memorial Hospital at Kaohsiung ( Site 4003)
🇨🇳Kaohsiung Niao Sung Dist, Kaohsiung, Taiwan
China Medical University Hospital ( Site 4007)
🇨🇳Taichung, Taiwan
Taichung Veterans General Hospital-Radiation Oncology ( Site 4008)
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital ( Site 4001)
🇨🇳Tainan, Taiwan
National Taiwan University Hospital ( Site 4000)
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital ( Site 4005)
🇨🇳Taipei, Taiwan
Chang Gung Medical Foundation-Linkou Branch ( Site 4006)
🇨🇳Taoyuan, Taiwan
Chulalongkorn University ( Site 4104)
🇹🇭Bangkok, Krung Thep Maha Nakhon, Thailand
Faculty of Medicine Siriraj Hospital ( Site 4102)
🇹🇭Bangkok, Krung Thep Maha Nakhon, Thailand
Songklanagarind hospital ( Site 4105)
🇹🇭HatYai, Songkhla, Thailand
Adana Medical Park Seyhan Hastanesi-Medikal Onkoloji ( Site 3417)
🇹🇷Adana, Turkey
Hacettepe Universite Hastaneleri-oncology hospital ( Site 3402)
🇹🇷Ankara, Turkey
Memorial Ankara Hastanesi-Medical Oncology ( Site 3408)
🇹🇷Ankara, Turkey
Ankara Bilkent City Hospital-Medical Oncology ( Site 3405)
🇹🇷Ankara, Turkey
Atatürk Üniversitesi-onkoloji ( Site 3416)
🇹🇷Erzurum, Turkey
TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 3403)
🇹🇷Istanbul, Turkey
I.E.U. Medical Point Hastanesi-Oncology ( Site 3406)
🇹🇷Izmir, Turkey