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

• ClinicalTrials.gov Identifier: NCT02559687
• Recruitment Status: Completed
• First Posted: September 24, 2015
• Results First Posted: July 17, 2019
• Last Update Posted: November 11, 2021
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: September 23, 2015
• First Posted Date: September 24, 2015
• Results First Submitted Date: June 27, 2019
• Results First Posted Date: July 17, 2019
• Last Update Posted Date: November 11, 2021
• Actual Study Start Date: December 2, 2015
• Actual Primary Completion Date: July 30, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 27, 2019)

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) [ Time Frame: Up to approximately 28 months ]

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.

• Original Primary Outcome Measures (submitted: September 23, 2015): Overall Response Rate [ Time Frame: Up to 2 years ]

Current Secondary Outcome Measures (submitted: June 27, 2019)

• Number of Participants Who Experienced an Adverse Event (AE) [ Time Frame: Up to approximately 28 months ]
  An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product, was also an adverse event. The number of participants who experienced ≥1 AE was reported.
• Number of Participants That Discontinued Study Treatment Due to an AE [ Time Frame: Up to approximately 24 months ]
  An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product, was also an adverse event. The number of participants that discontinued study treatment due to an AE was reported.
• Duration of Response (DOR) According to RECIST 1.1 Assessed by BICR [ Time Frame: Up to approximately 28 months ]
  For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. DOR assessments were based on blinded central imaging review with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR was reported.
• Progression Free Survival (PFS) According to RECIST 1.1 Assessed by BICR [ Time Frame: Up to approximately 28 months ]
  PFS was defined as the time from first day of study treatment to the first documented PD or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of ≥1 new lesions was also considered PD. PFS as assessed by blinded independent central review per RECIST 1.1 was reported.
• Overall Survival (OS) [ Time Frame: Up to approximately 28 months ]
  OS was defined as the time from first day of study treatment to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Pembrolizumab (MK-3475) in Previously-Treated Participants With Advanced Carcinoma of the Esophagus or Esophagogastric Junction (MK-3475-180/KEYNOTE-180)
• Official Title: A Phase II Study of Pembrolizumab Monotherapy in Third Line Previously Treated Subjects With Advanced/Metastatic Adenocarcinoma or Squamous Cell Carcinoma of the Esophagus or Advanced/Metastatic Siewert Type I Adenocarcinoma of the Esophagogastric Junction (KEYNOTE-180)
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Esophageal Carcinoma
• Esophagogastric Junction Carcinoma

Intervention

Biological: pembrolizumab

IV Q3W

Other Name: MK-3475

Study Arms

Experimental: Pembrolizumab 200 mg

Participants receive pembrolizumab 200 mg, intravenously (IV), every 3 weeks (Q3W) for up to 35 treatments (approximately 2 years)

Intervention: Biological: pembrolizumab

Publications *

• 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. [Epub ahead of print]
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 18, 2017): 121
• Original Estimated Enrollment (submitted: September 23, 2015): 100
• Actual Study Completion Date: October 29, 2021
• Actual Primary Completion Date: July 30, 2018 (Final data collection date for primary outcome measure)

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 a 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: Australia, Denmark, France, Germany, Japan, Korea, Republic of, Norway, United Kingdom, United States

Administrative Information

• NCT Number: NCT02559687
• Other Study ID Numbers: 3475-180; 2015-002427-26 ( EudraCT Number ); 163188 ( Registry Identifier: JAPIC-CTI ); MK-3475-180 ( Other Identifier: Merck ); KEYNOTE -180 ( Other Identifier: Merck )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: November 2021