Clinical Trial: NCT02494583 - My Cancer Genome

NCT02494583

Description:

This is a study of pembrolizumab (MK-3475) as first-line treatment for participants with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. Participants whose tumors express programmed death-ligand 1 (PD-L1) will be randomly assigned to one of the three treatment arms of the study: pembrolizumab as monotherapy [pembro mono], pembrolizumab plus standard of care (SOC) chemotherapy with cisplatin plus 5-fluorouracil (5-FU) or capecitabine [pembro combo], or placebo plus SOC chemotherapy with cisplatin plus 5-fluorouracil (5-FU) or capecitabine [SOC]. The primary study hypotheses are that pembrolizumab in combination with SOC chemotherapy is superior to SOC chemotherapy alone in terms of Progression-free Survival (PFS) and Overall Survival (OS) in participants with PD-L1 Combined Positive Score (CPS) ≥1, pembrolizumab in combination with SOC chemotherapy is superior to SOC chemotherapy alone in terms of OS in participants with PD-L1 CPS ≥10, pembrolizumab monotherapy is non-inferior to SOC chemotherapy alone in terms of OS in participants with PD-L1 CPS ≥1, and pembrolizumab monotherapy is superior to SOC chemotherapy alone in terms of OS in participants with PD-L1 CPS ≥1 and in participants with PD-L1 CPS ≥10.

Related Conditions:

Adenocarcinoma of the Gastroesophageal Junction
Gastric Adenocarcinoma

Recruiting Status:

Active, not recruiting

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT02494583

Trial Eligibility

Document

Title

Brief Title: Study of Pembrolizumab (MK-3475) as First-Line Monotherapy and Combination Therapy for Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (MK-3475-062/KEYNOTE-062)
Official Title: A Randomized, Active-Controlled, Partially Blinded, Biomarker Select, Phase III Clinical Trial of Pembrolizumab as Monotherapy and in Combination With Cisplatin+5-Fluorouracil Versus Placebo+Cisplatin+5-Fluorouracil as First-Line Treatment in Subjects With Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

Clinical Trial IDs

ORG STUDY ID: 3475-062
SECONDARY ID: 2015-000972-88
SECONDARY ID: 163187
SECONDARY ID: MK-3475-062
SECONDARY ID: KEYNOTE-062
NCT ID: NCT02494583

Conditions

Gastric Adenocarcinoma

Interventions

Drug	Synonyms	Arms
Pembrolizumab	MK-3475, KEYTRUDA®	Pembrolizumab + SOC Chemotherapy (Pembro Combo)
Cisplatin		Pembrolizumab + SOC Chemotherapy (Pembro Combo)
5-FU		Pembrolizumab + SOC Chemotherapy (Pembro Combo)
Capecitabine		Pembrolizumab + SOC Chemotherapy (Pembro Combo)
Placebo		Placebo + SOC Chemotherapy (SOC)

Purpose

Detailed Description

      As specified by the protocol, primary and secondary efficacy analyses will be evaluated in
      gastric cancer participants with PD-L1 CPS ≥1 (all participants) and PD-L1 CPS ≥10 (OS) by
      comparing the pembro mono arm or pembro combo arm separately to the SOC arm.

Trial Arms

Name	Type	Description	Interventions
Pembrolizumab Monotherapy (Pembro Mono)	Experimental	Participants receive pembrolizumab 200 mg, intravenously (IV) on Day 1 of each 3-week cycle (Q3W)	Pembrolizumab
Pembrolizumab + SOC Chemotherapy (Pembro Combo)	Experimental	Participants receive pembrolizumab 200 mg Q3W plus cisplatin 80 mg/m^2 Q3W plus 5-FU 800 mg/m^2/day IV infusion on Days 1-5 Q3W. Capecitabine 1000 mg/m^2 twice a day (BID) on Days 1-14 Q3W may be substituted for 5-FU per local guidelines.	Pembrolizumab Cisplatin 5-FU Capecitabine
Placebo + SOC Chemotherapy (SOC)	Placebo Comparator	Participants receive placebo IV Q3W plus cisplatin 80 mg/m^2 Q3W plus 5-FU 800 mg/m^2/day IV infusion on Days 1-5 Q3W. Capecitabine 1000 mg/m^2 BID on Days 1-14 Q3W may be substituted for 5-FU per local guidelines.	Cisplatin 5-FU Capecitabine Placebo

Eligibility Criteria

        Inclusion Criteria:

          -  Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale within 3 days prior to first dose of study medication

          -  Has histologically- or cytologically-confirmed diagnosis of locally advanced
             unresectable or metastatic gastric or GEJ adenocarcinoma

          -  Human epidermal growth factor receptor 2- (HER2/neu-) negative and programmed cell
             death ligand 1 (PD-L1)-positive

          -  Has measurable disease

          -  Female participants of childbearing potential must be willing to use adequate
             contraception or be surgically sterile, or abstain from heterosexual activity for the
             course of the study through 120 days after the last dose of study medication

          -  Male participants of childbearing potential should agree to use an adequate method of
             contraception starting with the first dose of study medication through 120 days after
             the last dose of study medication

          -  Adequate organ function

        Exclusion Criteria:

          -  Squamous cell or undifferentiated gastric cancer

          -  Previous therapy for locally advanced, unresectable or metastatic gastric/GEJ cancer.
             Participant may have received prior neoadjuvant or adjuvant therapy as long as it was
             completed at least 6 months prior to randomization

          -  Major surgery, open biopsy or significant traumatic injury within 28 days prior to
             randomization, or anticipation of the need for major surgery during the course of
             study treatment.

          -  Radiotherapy within 14 days of randomization

          -  Known additional malignancy that is progressing or requires active treatment with the
             exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin
             that has undergone potentially curative therapy or in situ cervical cancer

          -  Known active central nervous system (CNS) metastases and/or carcinomatous meningitis

          -  Active autoimmune disease that has required systemic treatment in past 2 years

          -  Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in
             dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
             immunosuppressive therapy within 7 days prior the first dose of study medication

          -  History of non-infectious pneumonitis that required steroids or current pneumonitis

          -  Active infection requiring systemic therapy

          -  Pregnant, breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the screening visit through 120 days
             after the last dose of study medication

          -  Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, or anti-PD-L2
             agent

          -  Known history of human immunodeficiency virus (HIV)

          -  Known active Hepatitis B or C

          -  Currently participating in and receiving study therapy or has participated in a study
             of an investigational agent or has used an investigational device within 4 weeks prior
             to the first dose of study medication

          -  Received a live vaccine within 30 days prior to the first dose of study medication

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Pembro Combo vs SOC: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With PD-L1 CPS ≥1 (All Participants)
Time Frame:	Up to approximately 36 months (through Interim Analysis cut-off date of 26-Sep-2018)
Safety Issue:
Description:	PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the SOC arm as a pre-specified primary analysis of the Intent-To-Treat (ITT) population. PFS is reported here for all participants in the pembro combo arm and SOC arm who were PD-L1 CPS ≥1 (all participants). Per protocol, PFS was compared separately between CPS ≥1 participants of the pembro mono arm and SOC arm and is presented later in the record.

Secondary Outcome Measures

Measure:	Pembro Combo vs SOC: Objective Response Rate (ORR) Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants)
Time Frame:	Up to approximately 42 months (through Final Analysis cut-off date of 26-Mar-2019)
Safety Issue:
Description:	ORR was defined as the percentage of participants in the analysis population who have a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro combo arm was compared to the SOC arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR for all participants in the pembro combo arm and SOC arm who were PD-L1 CPS ≥1 (all participants). Per protocol, ORR was compared separately between CPS ≥1 participants of the pembro mono arm and SOC arm and is presented later in the record.

Measure:	Pembro Combo vs SOC: Duration of Response (DOR) Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants)
Time Frame:	Up to approximately 42 months (through Final Analysis cut-off date of 26-Mar-2019)
Safety Issue:
Description:	For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 based upon BICR, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. DOR is reported here for all participants in the pembro combo arm and SOC arm who were PD-L1 CPS ≥1 (all participants) and had CR or PR. Per protocol, DOR was compared separately between CPS ≥1 responders of the pembro mono arm and SOC arm and is presented later in the record.

Measure:	Pembro Mono vs SOC: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants)
Time Frame:	Up to approximately 42 months (through Final Analysis cut-off date of 26-Mar-2019)
Safety Issue:
Description:	ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro mono arm was compared to the SOC arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR for all participants in the pembro mono arm and SOC arm who were PD-L1 CPS ≥1 (all participants). Per protocol, ORR was compared separately between CPS ≥1 participants of the pembro combo arm and SOC arm and is presented earlier in the record.

Measure:	Pembro Mono vs SOC: DOR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants)
Time Frame:	Up to approximately 42 months (through Final Analysis cut-off date of 26-Mar-2019)
Safety Issue:
Description:	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 based upon BICR, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. DOR is reported here for all participants in the pembro mono arm and SOC arm who were PD-L1 CPS ≥1 (all participants) and had CR or PR. Per protocol, DOR was compared separately between CPS ≥1 responders of the pembro combo arm and SOC arm and is presented earlier in the record.

Measure:	Pembro Mono vs SOC: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants)
Time Frame:	Up to approximately 42 months (through Final Analysis cut-off date of 26-Mar-2019)
Safety Issue:
Description:	PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the SOC arm as a pre-specified secondary analysis of the ITT population. PFS is reported here for all participants in the pembro mono arm and SOC arm who were PD-L1 CPS ≥1 (all participants). Per protocol, PFS was compared separately between CPS ≥1 participants of the pembro combo arm and SOC arm and is presented earlier in the record.

Measure:	Pembro Mono vs SOC: Change From Baseline to Week 18 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score
Time Frame:	Baseline, Week 18
Safety Issue:
Description:	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the Quality of Life (QoL) question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was compared between all participants of the pembro mono arm and the SOC arm as a pre-specified secondary analysis. As specified by the protocol, change from baseline to Week 18 in the GHS/QoL combined score was compared separately between all participants of the pembro combo arm and SOC arm and is presented later in the record.

Measure:	Pembro Combo vs SOC: Change From Baseline to Week 18 in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score
Time Frame:	Baseline, Week 18
Safety Issue:
Description:	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the GHS question "How would you rate your overall health during the past week?" (Item 29) and the QoL question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was compared between all participants of the pembro combo arm and the SOC arm as a pre-specified secondary analysis. As specified by the protocol, change from baseline to Week 18 in the GHS/QoL combined score was compared separately between all participants of the pembro mono arm and SOC arm and is presented earlier in the record.

Measure:	Pembro Mono vs. SOC: Change From Baseline to Week 18 in EORTC QLQ-Module for Gastric Cancer (STO22) Pain Symptom Subscale Score
Time Frame:	Baseline, Week 18
Safety Issue:
Description:	EORTC-QLQ-STO22 is a 22-item questionnaire developed to assess QoL of gastric cancer participants. It consists of 5 multi-item subscales that assess dysphagia (3 items), dietary restriction (4 items), pain (4 items), upper gastro-esophageal symptoms (3 items), and emotional problems (3 items), and questions on dry mouth, taste, body image, and hair loss. Participant responses to the Pain symptom subscale (Items 34-37) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Per protocol, change from baseline to Week 18 in the EORTC-QLQ-STO22 Pain score was compared between the pembro mono arm and the SOC arm as a pre-specified secondary analysis. As specified by the protocol, change from baseline to Week 18 in the EORTC-QLQ-STO22 Pain score was compared separately between the pembro combo arm and SOC arm and is presented later in the record.

Measure:	Pembro Combo vs. SOC: Change From Baseline to Week 18 in EORTC QLQ-STO22 Pain Symptom Subscale Score
Time Frame:	Baseline, Week 18
Safety Issue:
Description:	EORTC-QLQ-STO22 is a 22-item questionnaire developed to assess QoL of gastric cancer participants. It consists of 5 multi-item subscales that assess dysphagia (3 items), dietary restriction (4 items), pain (4 items), upper gastro-esophageal symptoms (3 items), and emotional problems (3 items), and questions on dry mouth, taste, body image, and hair loss. Participant responses to the Pain symptom subscale (Items 34-37) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Per protocol, change from baseline to Week 18 in the EORTC-QLQ-STO22 Pain score was compared between the pembro combo arm and the SOC arm as a pre-specified secondary analysis. As specified by the protocol, change from baseline to Week 18 in the EORTC-QLQ-STO22 Pain score was compared separately between the pembro mono arm and SOC arm and is presented earlier in the record.

Measure:	Number of Participants Experiencing an Adverse Event (AE)
Time Frame:	Up to approximately 31.5 months
Safety Issue:
Description:	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily 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 an AE was reported for each arm according to the treatment received.

Measure:	Number of Participants Discontinuing Study Treatment Due to an AE
Time Frame:	Up to approximately 28.5 months
Safety Issue:
Description:	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily 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 discontinued study treatment due to an AE was reported for each arm according to the treatment received.

Details

Phase:	Phase 3
Primary Purpose:	Interventional
Overall Status:	Active, not recruiting
Lead Sponsor:	Merck Sharp & Dohme Corp.

Trial Keywords

Gastric carcinoma
Gastric cancer
Gastroesophageal junction cancer
Gastroesophageal junction carcinoma
Programmed Cell Death-1 (PD1, PD-1),
Programmed Death-Ligand 1 (PDL1, PD-L1)
Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2)

Last Updated

March 10, 2021

Clinical Trials /

Study of Pembrolizumab (MK-3475) as First-Line Monotherapy and Combination Therapy for Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (MK-3475-062/KEYNOTE-062)