Study of Pembrolizumab (MK-3475) in Previously-Treated Participants With Advanced Carcinoma of the Esophagus or Esophagogastric Junction (MK-3475-180/KEYNOTE-180)

NCT ID: NCT02559687

Last Updated: 2022-09-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 121 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-02
• Study Completion Date: 2021-10-29

Brief Summary

In this study participants with advanced/metastatic adenocarcinoma of the esophagus (EAC), squamous cell carcinoma of the esophagus (ESCC), or advanced/metastatic Siewert type I adenocarcinoma of the esophagogastric junction (EGJ), who had been previously treated with two standard therapies, will be treated with pembrolizumab.

Conditions

Esophageal Carcinoma; Esophagogastric Junction Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pembrolizumab 200 mg

Participants will receive pembrolizumab 200 mg, intravenously (IV), every 3 weeks (Q3W) for up to 35 treatments (approximately 2 years). Eligible participants who stop pembrolizumab with Stable Disease (SD) or better but progress after discontinuation may be able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.

Group Type: EXPERIMENTAL

pembrolizumab

Intervention Type: BIOLOGICAL

IV Q3W

Interventions

pembrolizumab

IV Q3W

Intervention Type: BIOLOGICAL

Other Intervention Names

MK-3475

Eligibility Criteria

Inclusion Criteria

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy greater than 3 months
• Histologically-proven advanced/metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the EGJ
• Documented objective radiographic or clinical disease progression on two previous lines of standard therapy
• Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
• Can provide either a newly obtained or archival tumor tissue sample for intratumoral immune-related testing and for anti-programmed cell death (PD-1)
• Female participants of childbearing potential must be willing to use adequate contraception for the course of the study through 120 days after the last dose of study medication
• Male participants must agree to use adequate contraception starting with the first dose through 120 days after the last dose of study medication
• Adequate organ function

Exclusion Criteria

• Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study medication
• Has active autoimmune disease that has required systemic treatment within the 2 years prior to the first dose of study medication
• Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
• Known central nervous system (CNS) metastases and/or carcinomatous meningitis
• Prior anti-cancer mAb, chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to first dose of study medication or not recovered from adverse events due to a previously administered agent
• Prior therapy with an anti-PD-1, anti-PD-Ligand 1 (PD-L1), or anti-PD-L2 agent, or previously participated in a Merck pembrolizumab (MK-3475) study
• Has a known additional malignancy that has progressed or required active treatment within the last 5 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, in-situ cervical cancer, and in-situ or intra-mucosal pharyngeal cancer
• Received a live vaccine within 30 days of the first dose of study medication
• Known history of Human Immunodeficiency Virus (HIV) infection
• Known active Hepatitis B or C
• History of non-infectious pneumonitis that required steroids or current pneumonitis
• Active infection requiring systemic therapy
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study medication

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Shah MA, Kojima T, Hochhauser D, Enzinger P, Raimbourg J, Hollebecque A, Lordick F, Kim SB, Tajika M, Lockhart AC, Arkenau HT, El-Hajbi F, Gupta M, Pfeiffer P, Bhagia P, Cao ZA, Lunceford J, Suryawanshi S, Ayers M, J Marton M, Kato K. T cell-inflamed gene expression profile and PD-L1 expression and pembrolizumab efficacy in advanced esophageal cancer. Future Oncol. 2022 Jul 19. doi: 10.2217/fon-2021-1134. Online ahead of print.

Reference Type: DERIVED

PMID: 35852104 (View on PubMed)

Shah MA, Kojima T, Hochhauser D, Enzinger P, Raimbourg J, Hollebecque A, Lordick F, Kim SB, Tajika M, Kim HT, Lockhart AC, Arkenau HT, El-Hajbi F, Gupta M, Pfeiffer P, Liu Q, Lunceford J, Kang SP, Bhagia P, Kato K. Efficacy and Safety of Pembrolizumab for Heavily Pretreated Patients With Advanced, Metastatic Adenocarcinoma or Squamous Cell Carcinoma of the Esophagus: The Phase 2 KEYNOTE-180 Study. JAMA Oncol. 2019 Apr 1;5(4):546-550. doi: 10.1001/jamaoncol.2018.5441.

Reference Type: DERIVED

PMID: 30570649 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://merckoncologyclinicaltrials.com

Merck Oncology Clinical Trials Information

Other Identifiers

163188

Identifier Type: REGISTRY

Identifier Source: secondary_id

MK-3475-180

Identifier Type: OTHER

Identifier Source: secondary_id

KEYNOTE -180

Identifier Type: OTHER

Identifier Source: secondary_id

2015-002427-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

3475-180

Identifier Type: -

Identifier Source: org_study_id