Clinical trial NCT02559687: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2015-09-24
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: 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)
timeFrame: Up to approximately 28 months
Secondary outcomes:
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 59 months
measure: Number of Participants That Discontinued Study Treatment Due to an AE
timeFrame: Up to approximately 24 months
measure: Duration of Response (DOR) According to RECIST 1.1 Assessed by BICR
timeFrame: Up to approximately 67 months
measure: Progression Free Survival (PFS) According to RECIST 1.1 Assessed by BICR
timeFrame: Up to approximately 67 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 67 months
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.