Back to resultsA Study of Pembrolizumab (MK-3475) Versus Paclitaxel for Participants With Advanced Gastric/Gastroesophageal Junction Adenocarcinoma That Progressed After Therapy With Platinum and Fluoropyrimidine (MK-3475-061/KEYNOTE-061)
Primary Purpose
Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
pembrolizumab
paclitaxel
Sponsored by
About this trial
This is an interventional treatment trial for Gastric Adenocarcinoma focused on measuring Gastric cancer, Gastroesophageal junction cancer, PD1, PD-1, PDL1, PD-L1
Eligibility Criteria
Inclusion Criteria:
- Histologically- or cytologically-confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma
- Confirmed metastatic or locally advanced, unresectable disease (by computed tomography [CT] scan or clinical evidence)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Progression on or after prior first-line therapy containing any platinum/fluoropyrimidine doublet
- Willing to provide tumor tissue for PD-L1 biomarker analysis (new or archived specimens with agreement of Sponsor). As of 20 March 2016, participants must be PD-L1 positive to be enrolled.
- Human epidermal growth factor receptor 2 (HER-2/neu) status known and participants with HER2/neu positive tumors show documentation of disease progression on treatment containing trastuzumab
- Female participants of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of pembrolizumab or through 180 days after the last dose of paclitaxel.
- Male participants should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of pembrolizumab or through 180 days after the last dose of paclitaxel.
- Adequate organ function
Exclusion Criteria:
- Currently participating and receiving study therapy, or participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of medication
- Squamous cell or undifferentiated gastric cancer
- Active autoimmune disease that has required systemic treatment in past 2 years (replacement therapy is not considered a form of systemic treatment
- 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
- Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not recovered from AEs due to agents administered more than 4 weeks earlier
- Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not recovered from adverse events due to a previously administered agent or surgery
- 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, or in situ cervical cancer that has undergone potentially curative therapy)
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- History of (noninfectious) 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 trial
- Pregnant or 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 pembrolizumab or through 180 days after the last dose of paclitaxel.
- Prior immunotherapy including anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or previously participated in Merck pembrolizumab (MK-3475) clinical trial
- Known history of human immunodeficiency virus (HIV)
- Known active Hepatitis B or Hepatitis C
- Live vaccine within 30 days of planned start of study therapy
- Known allergy or hypersensitivity to paclitaxel or any components used in the paclitaxel preparation or other contraindication for taxane therapy
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Pembrolizumab
Paclitaxel
Arm Description
Participants receive 200 mg intravenous (IV) pembrolizumab on Day 1 of each 21-day cycle, for up to 35 administrations (approximately 2 years).
Participants receive 80 mg/m^2 IV paclitaxel on Days 1, 8, and 15 of each 28-day cycle, until disease progression or unacceptable toxicity.
Outcomes
Primary Outcome Measures
Progression-free Survival (PFS) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR) in Programmed Death-Ligand 1 (PD-L1) Positive Participants
PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs first. According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% confidence interval [CI]) in months was reported for PD-L1 positive participants by treatment group.
Overall Survival (OS) in PD-L1 Positive Participants
OS was defined as the time from randomization 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 analyzed using the Kaplan-Meier method and median OS (95% CI) in months was reported for PD-L1 positive participants by treatment group.
Secondary Outcome Measures
PFS According to RECIST 1.1 Based on BICR in All Participants
PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs first. According to RECIST 1.1, PD was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% CI) in months was reported for all participants by treatment group.
OS in All Participants
OS was defined as the time from randomization 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 analyzed using the Kaplan-Meier method and median OS (95% CI) in months was reported for all participants by treatment group.
PFS According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants
PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator assessment, or death due to any cause, whichever occurs first. According to RECIST 1.1, PD was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% CI) in months was reported for PD-L1 positive participants by treatment group.
PFS According to RECIST 1.1 Based on Investigator Assessment in All Participants
PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator assessment, or death due to any cause, whichever occurs first. According to RECIST 1.1, PD was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% CI) in months was reported for all participants by treatment group.
PFS According to Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) Based on BICR in PD-L1 Positive Participants
PFS defined as time from randomization to first documented PD per irRECIST based on BICR, or death due to any cause, whichever occurs first. Following initial PD by RECIST 1.1 (20% relative increase in SOD of target lesions), participants were assessed according to irRECIST: tumor assessment was repeated ≥4 weeks later to confirm PD with the option of continuing treatment until this scan was obtained for clinically stable participants. If PD confirmed, participant was discontinued from treatment unless investigator determined benefit. If repeat scan indicated stable disease (SD; neither sufficient shrinkage or increase of target lesion), partial response (PR; ≥30% decrease in the SOD of target lesions), or complete response (CR; disappearance of all non-nodal target lesions), participant could continue treatment at investigator's discretion. PFS analyzed using Kaplan-Meier method and median PFS (95% CI) in months was reported for PD-L1 positive participants by treatment group.
PFS According to irRECIST Based on BICR in All Participants
PFS defined as time from randomization to first documented PD per irRECIST based on BICR, or death due to any cause, whichever occurs first. Following initial PD by RECIST 1.1 (20% relative increase in SOD of target lesions), participants were assessed according to irRECIST: tumor assessment was repeated ≥4 weeks later to confirm PD with the option of continuing treatment until this scan was obtained for clinically stable participants. If PD confirmed, participant was discontinued from treatment unless investigator determined benefit. If repeat scan indicated SD (neither sufficient shrinkage or increase of target lesion), PR (≥30% decrease in the SOD of target lesions), or CR (disappearance of all non-nodal target lesions), participant could continue treatment at investigator's discretion. PFS analyzed using Kaplan-Meier method and median PFS (95% CI) in months was reported for all participants by treatment group.
Time to Tumor Progression (TTP) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants
TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR. Using RECIST 1.1, progressive disease was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions. If there was no documented disease progression, TTP was censored at last tumor assessment date. TTP was analyzed using the Kaplan-Meier method and median TTP (95% CI) in months was reported for PD-L1 positive participants by treatment group.
TTP According to RECIST 1.1 Based on BICR in All Participants
TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR. Using RECIST 1.1, progressive disease was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions. If there was no documented disease progression, TTP was censored at last tumor assessment date. TTP was analyzed using the Kaplan-Meier method and median TTP (95% CI) in months was reported for all participants by treatment group.
TTP According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants
TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator assessment. Using RECIST 1.1, progressive disease was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions. If there was no documented disease progression, TTP was censored at last tumor assessment date. TTP was analyzed using the Kaplan-Meier method and median TTP (95% CI) in months was reported for PD-L1 positive participants by treatment group.
TTP According to RECIST 1.1 Based on Investigator Assessment in All Participants
TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator assessment. Using RECIST 1.1, progressive disease was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions. If there was no documented disease progression, TTP was censored at last tumor assessment date. TTP was analyzed using the Kaplan-Meier method and median TTP (95% CI) in months was reported for all participants by treatment group.
Objective Response Rate (ORR) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants
ORR was defined as the percentage of the participants in the analysis population who had a confirmed CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on BICR. ORR was analyzed using the stratified Miettinen and Nurminen method, and reported with 95% CI for PD-L1 positive participants by treatment group.
ORR According to RECIST 1.1 Based on BICR in All Participants
ORR was defined as the percentage of the participants in the analysis population who had a confirmed CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on BICR. ORR was analyzed using the stratified Miettinen and Nurminen method, and reported with 95% CI for all participants by treatment group.
ORR According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants
ORR was defined as the percentage of the participants in the analysis population who had a confirmed CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on investigator assessment. ORR was analyzed using the stratified Miettinen and Nurminen method, and reported with 95% CI for PD-L1 positive participants by treatment group.
ORR According to RECIST 1.1 Based on Investigator Assessment in All Participants
ORR was defined as the percentage of the participants in the analysis population who had a confirmed CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on investigator assessment. ORR was analyzed using the stratified Miettinen and Nurminen method, and reported with 95% CI for all participants by treatment group.
Duration of Response (DOR) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants
For PD-L1 positive participants who demonstrated CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on BICR, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs 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. DOR was analyzed using the Kaplan-Meier method and median DOR (range) in months was reported for PD-L1 positive participants with response by treatment group.
DOR According to RECIST 1.1 Based on BICR in All Participants
For participants who demonstrated CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on BICR, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs 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. DOR was analyzed using the Kaplan-Meier method and median DOR (range) in months was reported for all participants with response by treatment group.
DOR According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants
For PD-L1 positive participants who demonstrated CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on investigator assessment, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs 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. DOR was analyzed using the Kaplan-Meier method and median DOR (range) in months was reported for PD-L1 positive participants with response by treatment group.
DOR According to RECIST 1.1 Based on Investigator Assessment in All Participants
For participants who demonstrated CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on investigator assessment, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs 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. DOR was analyzed using the Kaplan-Meier method and median DOR (range) in months was reported for all participants with response by treatment group.
Percentage of PD-L1 Positive 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 does 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 AE. The percentage of participants with at least one AE was reported for PD-L1 positive participants by treatment group.
Percentage of All Participants Who Experienced an AE
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does 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 AE. The percentage of participants with at least one AE was reported for all participants by treatment group.
Percentage of PD-L1 Positive Participants That Discontinued Study Treatment Due to AE
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does 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 AE. The percentage of participants that discontinued study treatment due to an AE was reported for PD-L1 positive participants by treatment group.
Percentage of All Participants That Discontinued Study Treatment Due to AE
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does 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 AE. The percentage of participants that discontinued study treatment due to an AE was reported for all participants by treatment group.
Full Information
NCT ID
NCT02370498
First Posted
February 23, 2015
Last Updated
May 12, 2022
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT02370498
Brief Title
A Study of Pembrolizumab (MK-3475) Versus Paclitaxel for Participants With Advanced Gastric/Gastroesophageal Junction Adenocarcinoma That Progressed After Therapy With Platinum and Fluoropyrimidine (MK-3475-061/KEYNOTE-061)
Official Title
A Phase III, Randomized, Open-label Clinical Trial of Pembrolizumab (MK-3475) Versus Paclitaxel in Subjects With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma Who Progressed After First-Line Therapy With Platinum and Fluoropyrimidine
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
May 11, 2015 (Actual)
Primary Completion Date
October 26, 2017 (Actual)
Study Completion Date
June 10, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a study for participants with advanced gastric or gastroesophageal junction adenocarcinoma who have had tumor progression after first-line treatment with platinum and fluoropyrimidine doublet therapy. The primary study hypotheses are that pembrolizumab (MK-3475) prolongs progression free survival (PFS) and overall survival (OS) for participants with tumors that show positive programmed cell death ligand 1 (PD-L1) expression.
As of 20-March-2016, enrollment will be limited to PD-L1 positive participants.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma
Keywords
Gastric cancer, Gastroesophageal junction cancer, PD1, PD-1, PDL1, PD-L1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
592 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pembrolizumab
Arm Type
Experimental
Arm Description
Participants receive 200 mg intravenous (IV) pembrolizumab on Day 1 of each 21-day cycle, for up to 35 administrations (approximately 2 years).
Arm Title
Paclitaxel
Arm Type
Active Comparator
Arm Description
Participants receive 80 mg/m^2 IV paclitaxel on Days 1, 8, and 15 of each 28-day cycle, until disease progression or unacceptable toxicity.
Intervention Type
Biological
Intervention Name(s)
pembrolizumab
Other Intervention Name(s)
MK-3475
Intervention Description
200 mg administered as IV infusion on Day 1 of each 21-day cycle.
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Other Intervention Name(s)
TAXOL®
Intervention Description
80 mg/m^2 administered as IV infusion on Days 1, 8, and 15 of each 28-day cycle.
Primary Outcome Measure Information:
Title
Progression-free Survival (PFS) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR) in Programmed Death-Ligand 1 (PD-L1) Positive Participants
Description
PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs first. According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% confidence interval [CI]) in months was reported for PD-L1 positive participants by treatment group.
Time Frame
Up to 30 months (through database cut-off date of 26 Oct 2017)
Title
Overall Survival (OS) in PD-L1 Positive Participants
Description
OS was defined as the time from randomization 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 analyzed using the Kaplan-Meier method and median OS (95% CI) in months was reported for PD-L1 positive participants by treatment group.
Time Frame
Up to 30 months (through database cut-off date of 26 Oct 2017)
Secondary Outcome Measure Information:
Title
PFS According to RECIST 1.1 Based on BICR in All Participants
Description
PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs first. According to RECIST 1.1, PD was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% CI) in months was reported for all participants by treatment group.
Time Frame
Up to 30 months (through database cut-off date of 26 Oct 2017)
Title
OS in All Participants
Description
OS was defined as the time from randomization 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 analyzed using the Kaplan-Meier method and median OS (95% CI) in months was reported for all participants by treatment group.
Time Frame
Up to 30 months (through database cut-off date of 26 Oct 2017)
Title
PFS According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants
Description
PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator assessment, or death due to any cause, whichever occurs first. According to RECIST 1.1, PD was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% CI) in months was reported for PD-L1 positive participants by treatment group.
Time Frame
Up to 30 months (through database cut-off date of 26 Oct 2017)
Title
PFS According to RECIST 1.1 Based on Investigator Assessment in All Participants
Description
PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator assessment, or death due to any cause, whichever occurs first. According to RECIST 1.1, PD was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% CI) in months was reported for all participants by treatment group.
Time Frame
Up to 30 months (through database cut-off date of 26 Oct 2017)
Title
PFS According to Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) Based on BICR in PD-L1 Positive Participants
Description
PFS defined as time from randomization to first documented PD per irRECIST based on BICR, or death due to any cause, whichever occurs first. Following initial PD by RECIST 1.1 (20% relative increase in SOD of target lesions), participants were assessed according to irRECIST: tumor assessment was repeated ≥4 weeks later to confirm PD with the option of continuing treatment until this scan was obtained for clinically stable participants. If PD confirmed, participant was discontinued from treatment unless investigator determined benefit. If repeat scan indicated stable disease (SD; neither sufficient shrinkage or increase of target lesion), partial response (PR; ≥30% decrease in the SOD of target lesions), or complete response (CR; disappearance of all non-nodal target lesions), participant could continue treatment at investigator's discretion. PFS analyzed using Kaplan-Meier method and median PFS (95% CI) in months was reported for PD-L1 positive participants by treatment group.
Time Frame
Up to 30 months (through database cut-off date of 26 Oct 2017)
Title
PFS According to irRECIST Based on BICR in All Participants
Description
PFS defined as time from randomization to first documented PD per irRECIST based on BICR, or death due to any cause, whichever occurs first. Following initial PD by RECIST 1.1 (20% relative increase in SOD of target lesions), participants were assessed according to irRECIST: tumor assessment was repeated ≥4 weeks later to confirm PD with the option of continuing treatment until this scan was obtained for clinically stable participants. If PD confirmed, participant was discontinued from treatment unless investigator determined benefit. If repeat scan indicated SD (neither sufficient shrinkage or increase of target lesion), PR (≥30% decrease in the SOD of target lesions), or CR (disappearance of all non-nodal target lesions), participant could continue treatment at investigator's discretion. PFS analyzed using Kaplan-Meier method and median PFS (95% CI) in months was reported for all participants by treatment group.
Time Frame
Up to 30 months (through database cut-off date of 26 Oct 2017)
Title
Time to Tumor Progression (TTP) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants
Description
TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR. Using RECIST 1.1, progressive disease was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions. If there was no documented disease progression, TTP was censored at last tumor assessment date. TTP was analyzed using the Kaplan-Meier method and median TTP (95% CI) in months was reported for PD-L1 positive participants by treatment group.
Time Frame
Up to 30 months (through database cut-off date of 26 Oct 2017)
Title
TTP According to RECIST 1.1 Based on BICR in All Participants
Description
TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR. Using RECIST 1.1, progressive disease was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions. If there was no documented disease progression, TTP was censored at last tumor assessment date. TTP was analyzed using the Kaplan-Meier method and median TTP (95% CI) in months was reported for all participants by treatment group.
Time Frame
Up to 30 months (through database cut-off date of 26 Oct 2017)
Title
TTP According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants
Description
TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator assessment. Using RECIST 1.1, progressive disease was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions. If there was no documented disease progression, TTP was censored at last tumor assessment date. TTP was analyzed using the Kaplan-Meier method and median TTP (95% CI) in months was reported for PD-L1 positive participants by treatment group.
Time Frame
Up to 30 months (through database cut-off date of 26 Oct 2017)
Title
TTP According to RECIST 1.1 Based on Investigator Assessment in All Participants
Description
TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator assessment. Using RECIST 1.1, progressive disease was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions. If there was no documented disease progression, TTP was censored at last tumor assessment date. TTP was analyzed using the Kaplan-Meier method and median TTP (95% CI) in months was reported for all participants by treatment group.
Time Frame
Up to 30 months (through database cut-off date of 26 Oct 2017)
Title
Objective Response Rate (ORR) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants
Description
ORR was defined as the percentage of the participants in the analysis population who had a confirmed CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on BICR. ORR was analyzed using the stratified Miettinen and Nurminen method, and reported with 95% CI for PD-L1 positive participants by treatment group.
Time Frame
Up to 30 months (through database cut-off date of 26 Oct 2017)
Title
ORR According to RECIST 1.1 Based on BICR in All Participants
Description
ORR was defined as the percentage of the participants in the analysis population who had a confirmed CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on BICR. ORR was analyzed using the stratified Miettinen and Nurminen method, and reported with 95% CI for all participants by treatment group.
Time Frame
Up to 30 months (through database cut-off date of 26 Oct 2017)
Title
ORR According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants
Description
ORR was defined as the percentage of the participants in the analysis population who had a confirmed CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on investigator assessment. ORR was analyzed using the stratified Miettinen and Nurminen method, and reported with 95% CI for PD-L1 positive participants by treatment group.
Time Frame
Up to 30 months (through database cut-off date of 26 Oct 2017)
Title
ORR According to RECIST 1.1 Based on Investigator Assessment in All Participants
Description
ORR was defined as the percentage of the participants in the analysis population who had a confirmed CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on investigator assessment. ORR was analyzed using the stratified Miettinen and Nurminen method, and reported with 95% CI for all participants by treatment group.
Time Frame
Up to 30 months (through database cut-off date of 26 Oct 2017)
Title
Duration of Response (DOR) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants
Description
For PD-L1 positive participants who demonstrated CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on BICR, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs 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. DOR was analyzed using the Kaplan-Meier method and median DOR (range) in months was reported for PD-L1 positive participants with response by treatment group.
Time Frame
Up to 30 months (through database cut-off date of 26 Oct 2017)
Title
DOR According to RECIST 1.1 Based on BICR in All Participants
Description
For participants who demonstrated CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on BICR, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs 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. DOR was analyzed using the Kaplan-Meier method and median DOR (range) in months was reported for all participants with response by treatment group.
Time Frame
Up to 30 months (through database cut-off date of 26 Oct 2017)
Title
DOR According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants
Description
For PD-L1 positive participants who demonstrated CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on investigator assessment, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs 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. DOR was analyzed using the Kaplan-Meier method and median DOR (range) in months was reported for PD-L1 positive participants with response by treatment group.
Time Frame
Up to 30 months (through database cut-off date of 26 Oct 2017)
Title
DOR According to RECIST 1.1 Based on Investigator Assessment in All Participants
Description
For participants who demonstrated CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on investigator assessment, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs 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. DOR was analyzed using the Kaplan-Meier method and median DOR (range) in months was reported for all participants with response by treatment group.
Time Frame
Up to 30 months (through database cut-off date of 26 Oct 2017)
Title
Percentage of PD-L1 Positive Participants Who Experienced an Adverse Event (AE)
Description
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does 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 AE. The percentage of participants with at least one AE was reported for PD-L1 positive participants by treatment group.
Time Frame
Up to 71 months (through database cut-off date of 10 Jun 2021)
Title
Percentage of All Participants Who Experienced an AE
Description
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does 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 AE. The percentage of participants with at least one AE was reported for all participants by treatment group.
Time Frame
Up to 71 months (through database cut-off date of 10 Jun 2021)
Title
Percentage of PD-L1 Positive Participants That Discontinued Study Treatment Due to AE
Description
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does 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 AE. The percentage of participants that discontinued study treatment due to an AE was reported for PD-L1 positive participants by treatment group.
Time Frame
Up to approximately 26.4 months
Title
Percentage of All Participants That Discontinued Study Treatment Due to AE
Description
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does 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 AE. The percentage of participants that discontinued study treatment due to an AE was reported for all participants by treatment group.
Time Frame
Up to approximately 26.4 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically- or cytologically-confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma
Confirmed metastatic or locally advanced, unresectable disease (by computed tomography [CT] scan or clinical evidence)
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Progression on or after prior first-line therapy containing any platinum/fluoropyrimidine doublet
Willing to provide tumor tissue for PD-L1 biomarker analysis (new or archived specimens with agreement of Sponsor). As of 20 March 2016, participants must be PD-L1 positive to be enrolled.
Human epidermal growth factor receptor 2 (HER-2/neu) status known and participants with HER2/neu positive tumors show documentation of disease progression on treatment containing trastuzumab
Female participants of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of pembrolizumab or through 180 days after the last dose of paclitaxel.
Male participants should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of pembrolizumab or through 180 days after the last dose of paclitaxel.
Adequate organ function
Exclusion Criteria:
Currently participating and receiving study therapy, or participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of medication
Squamous cell or undifferentiated gastric cancer
Active autoimmune disease that has required systemic treatment in past 2 years (replacement therapy is not considered a form of systemic treatment
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
Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not recovered from AEs due to agents administered more than 4 weeks earlier
Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not recovered from adverse events due to a previously administered agent or surgery
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, or in situ cervical cancer that has undergone potentially curative therapy)
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
History of (noninfectious) 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 trial
Pregnant or 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 pembrolizumab or through 180 days after the last dose of paclitaxel.
Prior immunotherapy including anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or previously participated in Merck pembrolizumab (MK-3475) clinical trial
Known history of human immunodeficiency virus (HIV)
Known active Hepatitis B or Hepatitis C
Live vaccine within 30 days of planned start of study therapy
Known allergy or hypersensitivity to paclitaxel or any components used in the paclitaxel preparation or other contraindication for taxane therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
35101941
Citation
Cristescu R, Aurora-Garg D, Albright A, Xu L, Liu XQ, Loboda A, Lang L, Jin F, Rubin EH, Snyder A, Lunceford J. Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors. J Immunother Cancer. 2022 Jan;10(1):e003091. doi: 10.1136/jitc-2021-003091.
Results Reference
derived
PubMed Identifier
34468869
Citation
Fuchs CS, Ozguroglu M, Bang YJ, Di Bartolomeo M, Mandala M, Ryu MH, Fornaro L, Olesinski T, Caglevic C, Chung HC, Muro K, Van Cutsem E, Elme A, Thuss-Patience P, Chau I, Ohtsu A, Bhagia P, Wang A, Shih CS, Shitara K. Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial. Gastric Cancer. 2022 Jan;25(1):197-206. doi: 10.1007/s10120-021-01227-z. Epub 2021 Sep 1.
Results Reference
derived
PubMed Identifier
34363528
Citation
Van Cutsem E, Amonkar M, Fuchs CS, Alsina M, Ozguroglu M, Bang YJ, Chung HC, Muro K, Goekkurt E, Benson AB 3rd, Sun W, Wainberg ZA, Norquist JM, Chen X, Shih CS, Shitara K. Health-related quality of life in advanced gastric/gastroesophageal junction cancer with second-line pembrolizumab in KEYNOTE-061. Gastric Cancer. 2021 Nov;24(6):1330-1340. doi: 10.1007/s10120-021-01200-w. Epub 2021 Aug 7. Erratum In: Gastric Cancer. 2021 Sep 18;:
Results Reference
derived
PubMed Identifier
33792646
Citation
Chao J, Fuchs CS, Shitara K, Tabernero J, Muro K, Van Cutsem E, Bang YJ, De Vita F, Landers G, Yen CJ, Chau I, Elme A, Lee J, Ozguroglu M, Catenacci D, Yoon HH, Chen E, Adelberg D, Shih CS, Shah S, Bhagia P, Wainberg ZA. Assessment of Pembrolizumab Therapy for the Treatment of Microsatellite Instability-High Gastric or Gastroesophageal Junction Cancer Among Patients in the KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 Clinical Trials. JAMA Oncol. 2021 Jun 1;7(6):895-902. doi: 10.1001/jamaoncol.2021.0275.
Results Reference
derived
PubMed Identifier
29880231
Citation
Shitara K, Ozguroglu M, Bang YJ, Di Bartolomeo M, Mandala M, Ryu MH, Fornaro L, Olesinski T, Caglevic C, Chung HC, Muro K, Goekkurt E, Mansoor W, McDermott RS, Shacham-Shmueli E, Chen X, Mayo C, Kang SP, Ohtsu A, Fuchs CS; KEYNOTE-061 investigators. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018 Jul 14;392(10142):123-133. doi: 10.1016/S0140-6736(18)31257-1. Epub 2018 Jun 4.
Results Reference
derived
Links:
URL
http://merckoncologyclinicaltrials.com
Description
Merck Oncology Clinical Trials Information
Learn more about this trial
A Study of Pembrolizumab (MK-3475) Versus Paclitaxel for Participants With Advanced Gastric/Gastroesophageal Junction Adenocarcinoma That Progressed After Therapy With Platinum and Fluoropyrimidine (MK-3475-061/KEYNOTE-061)
We'll reach out to this number within 24 hrs