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

Esophageal Carcinoma Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02559687
• Other study ID #: 3475-180
• Secondary ID: 163188MK-3475-18
• Status: Completed
• Phase: Phase 2
• Start date: December 2, 2015
• Est. completion date: October 29, 2021

Study information

• Verified date: August 2022
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: October 29, 2021
• Est. primary completion date: July 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Esophageal Carcinoma
• Esophageal Neoplasms
• Esophagogastric Junction Carcinoma

Intervention

Biological:
• pembrolizumab
IV Q3W

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of Participants Who Experienced an Adverse Event (AE)	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 per protocol for the first course of treatment.	Up to approximately 59 months
Secondary	Number of Participants That Discontinued Study Treatment Due to an AE	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 per protocol for the first course of treatment.	Up to approximately 24 months
Secondary	Duration of Response (DOR) According to RECIST 1.1 Assessed by BICR	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 per protocol for the first course of treatment.	Up to approximately 67 months
Secondary	Progression Free Survival (PFS) According to RECIST 1.1 Assessed by BICR	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 per protocol for the first course of treatment.	Up to approximately 67 months
Secondary	Overall Survival (OS)	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. OS was reported per protocol for the first course of treatment	Up to approximately 67 months

External Links

•   Merck Oncology Clinical Trials Information