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

Overview

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.

Interventions

• Drug Paclitaxel
  80-100 mg/m\^2 IV infusion, administered on days 1, 8, and 15 of every 28-day cycle.
• Drug Irinotecan
  180 mg/m\^2 IV infusion, administered on day 1 of every 14-day cycle.
• Biological Pembrolizumab
  200 mg IV infusion, administered every Q3W up to 35 infusions.
• Biological MK-4830
  800 mg IV infusion, administered Q3W up to 35 infusions.
• Drug Lenvatinib
  20 mg oral administration every day.
• Biological Sacituzumab tirumotecan
  4 mg/kg or 5 mg/kg IV infusion on Days 1, 15, and 29 of each 42-day cycle.
• Drug Antihistamine
  Administered per product label.
• Drug H2 Receptor Antagonist
  Administered per product label.
• Drug Acetaminophen (or equivalent)
  Administered per product label.
• Drug Dexamethasone (or equivalent)
  Administered per product label.

Primary outcome measures

• Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) During Safety Lead-in Phase [Time frame: Up to approximately 3 weeks]
• Number of Participants Who Experienced an Adverse Event (AE) During Safety Lead-in Phase [Time frame: Up to approximately 3 weeks]
• Number of Participants Who Discontinue Study Treatment Due to an AE During Safety Lead-in Phase [Time frame: Up to approximately 3 weeks]
• Objective Response Rate (ORR) [Time frame: Up to approximately 48 months]

Secondary outcome measures (5)

• Progression-Free Survival (PFS) [Time frame: Up to approximately 70 months]
• Duration of Response (DOR) [Time frame: Up to approximately 70 months]
• Overall Survival (OS) [Time frame: Up to approximately 70 months]
• Number of Participants Experiencing at Least One Adverse Event (AE) During the Efficacy Phase [Time frame: Up to approximately 70 months]
• Number of Participants Who Discontinue Study Treatment Due to An AE During the Efficacy Phase [Time frame: Up to approximately 70 months]

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 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 8 centers

• Anhui Provincial Hospital ( Site 3501) — Hefei
• Beijing Cancer hospital-Digestive Oncology ( Site 3500) — Beijing
• The First Affiliated Hospital of Xiamen University ( Site 3516) — Xiamen
• The First Affiliated Hospital of Xinxiang Medical University-Oncology ( Site 3510) — Xinxiang
• Henan Cancer Hospital ( Site 3518) — Zhengzhou
• First Huai'an Hospital Affiliated to Nanjing Medical University ( Site 3506) — Huai'an
• Shanghai Chest Hospital-Esophageal surgery department ( Site 3513) — Shanghai
• Zhejiang Cancer Hospital-Thoracic oncology ( Site 3511) — Hangzhou

Taiwan · 7 centers

• Chang Gung Memorial Hospital at Kaohsiung ( Site 4003) — Kaohsiung Niao Sung Dist
• China Medical University Hospital ( Site 4007) — Taichung
• Taichung Veterans General Hospital-Radiation Oncology ( Site 4008) — Taichung
• National Cheng Kung University Hospital ( Site 4001) — Tainan
• National Taiwan University Hospital ( Site 4000) — Taipei
• Taipei Veterans General Hospital ( Site 4005) — Taipei
• Chang Gung Medical Foundation-Linkou Branch ( Site 4006) — Taoyuan

Turkey (Türkiye) · 7 centers

• Adana Medical Park Seyhan Hastanesi-Medikal Onkoloji ( Site 3417) — Adana
• Hacettepe Universite Hastaneleri-oncology hospital ( Site 3402) — Ankara
• Memorial Ankara Hastanesi-Medical Oncology ( Site 3408) — Ankara
• Ankara Bilkent City Hospital-Medical Oncology ( Site 3405) — Ankara
• Atatürk Üniversitesi-onkoloji ( Site 3416) — Erzurum
• TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 3403 — Istanbul
• I.E.U. Medical Point Hastanesi-Oncology ( Site 3406) — Izmir

Italy · 6 centers

• IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"-Oncologia Medica — Meldola
• Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Si — Milan
• Azienda Ospedaliero Universitaria Pisana ( Site 3206) — Pisa
• Istituto Oncologico Veneto IRCCS-Oncologia Medica 1 ( Site 3203) — Padova
• Ospedale San Raffaele-Oncologia Medica ( Site 3202) — Milan
• Istituto Europeo di Oncologia IRCCS-Divisione di Sviluppo di Nuovi Farmaci per Terapie Inn — Milan

United States · 5 centers

• University of Arizona Cancer Center-University of Arizona Cancer Center ( Site 4927) — Tucson
• UCLA Hematology/Oncology - Santa Monica ( Site 4905) — Los Angeles
• Hematology-Oncology Associates of Central NY, P.C. ( Site 4925) — East Syracuse
• Columbia University Irving Medical Center-CUIMC Herbert Irving Comprehensive Cancer Center — New York
• UPMC Hillman Cancer Center-UPMC ( Site 4904) — Pittsburgh

Germany · 5 centers

• Institut für Klinisch Onkologische Forschung-Klink für Onkologie und Hämatologie ( Site 48 — Frankfurt am Main
• Universitaetsklinikum Duesseldorf ( Site 4802) — Düsseldorf
• Universitaetsklinikum Carl Gustav Carus Dresden-Medical Dept I - Medical Oncology ( Site 4 — Dresden
• Charité Campus Virchow-Klinikum-Klinik Hämatologie Onkologie Tumorimmunologie ( Site 4804) — Berlin
• Facharztzentrum Eppendorf ( Site 4807) — Hamburg

Japan · 5 centers

• Aichi Cancer Center ( Site 3702) — Nagoya
• National Cancer Center Hospital East ( Site 3701) — Kashiwa
• Saitama Prefectural Cancer Center ( Site 3703) — Kitaadachi-gun
• Shizuoka Cancer Center ( Site 3704) — Nagaizumi-cho,Sunto-gun
• National Cancer Center Hospital ( Site 3700) — Chuo-ku

Chile · 4 centers

• FALP-UIDO ( Site 4400) — Santiago
• Centro de Oncología de Precisión-Oncology ( Site 4404) — Santiago
• Clínica las Condes ( Site 4403) — Santiago
• Clínica UC San Carlos de Apoquindo ( Site 4405) — Santiago

Brazil · 3 centers

• Liga Norte Riograndense Contra o Câncer ( Site 4303) — Natal
• Hospital Nossa Senhora da Conceição ( Site 4301) — Porto Alegre
• ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 4300) — São Paulo

Thailand · 3 centers

• Faculty of Medicine Siriraj Hospital ( Site 4102) — Bangkoknoi
• Chulalongkorn University ( Site 4104) — Pathumwan
• Songklanagarind hospital ( Site 4105) — Hat Yai

South Korea · 2 centers

• Asan Medical Center-Department of Oncology ( Site 3901) — Seoul
• Samsung Medical Center-Division of Hematology/Oncology ( Site 3900) — Seoul

Switzerland · 2 centers

• Hôpitaux Universitaires de Genève (HUG) ( Site 4702) — Geneva
• Kantonsspital Graubünden-Medizin ( Site 4700) — Chur

Norway · 1 center

• Oslo universitetssykehus, Radiumhospitalet ( Site 4501) — Oslo

Singapore · 1 center

• National University Hospital ( Site 3800) — Singapore

Identifiers

NCT: NCT05319730 · 3475-06B · jRCT2031220582 · 2023-505189-26-00 · U1111-1291-1987 · MK-3475-06B · KEYMAKER-U06B · 2021-005443-76

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗