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

NCT02559687 | Completed Phase 2 Results

• 5 other identifiers: 3475-180163188MK-3475-180KEYNOTE -1802015-002427-26
• Study Type: interventional
• Target: 121
• Locations: 0 countries
• Sites: N/A

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

Keywords

Programmed Cell Death-1 (PD-1, PD1); Programmed Cell Death-Ligand 1 (PD-L1, PDL1); Programmed Cell Death-Ligand 2 (PD-L2, PDL2)

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) According to Response Evaluation Criteria for Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR)

  ORR was defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a CR or PR based on modified RECIST 1.1 was reported per protocol for the first course of treatment.

  Up to approximately 28 months

Secondary Outcomes (5)

• Number of Participants Who Experienced an Adverse Event (AE)

  Up to approximately 59 months

• Number of Participants That Discontinued Study Treatment Due to an AE

  Up to approximately 24 months

• Duration of Response (DOR) According to RECIST 1.1 Assessed by BICR

  Up to approximately 67 months

• Progression Free Survival (PFS) According to RECIST 1.1 Assessed by BICR

  Up to approximately 67 months

• Overall Survival (OS)

  Up to approximately 67 months

Study Arms (1)

Pembrolizumab 200 mg

EXPERIMENTAL

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.

Biological: pembrolizumab

Interventions

pembrolizumab BIOLOGICAL

IV Q3W

Also known as: MK-3475

Pembrolizumab 200 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (2)

• 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.

  PMID: 35852104 DERIVED

• 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.

  PMID: 30570649 DERIVED

Related Links

• Merck Oncology Clinical Trials Information

MeSH Terms

Conditions

Esophageal Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2015
• First Posted: September 24, 2015
• Study Start: December 2, 2015
• Primary Completion: July 30, 2018
• Study Completion: October 29, 2021
• Last Updated: September 14, 2022
• Results First Posted: July 17, 2019

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share