Gastric AdenocarcinomaPhase 3NCT02370498
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)
A Phase 3 study testing pembrolizumab and paclitaxel in people with Gastric Adenocarcinoma and Gastroesophageal Junction Adenocarcinoma, run by Merck Sharp & Dohme LLC.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma
- What is being tested?
- pembrolizumab and paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 592 participants
- Where
- No sites listed yet
- Study dates
- 11 May 2015to 10 Jun 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
About this study
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
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.
- Being tested
- pembrolizumab, paclitaxel
- Keywords
- Gastric cancer, Gastroesophageal junction cancer, PD1, PD-1, PDL1, PD-L1
- Medical subject headings
- Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pembrolizumabBiological
Also called MK-3475
200 mg administered as IV infusion on Day 1 of each 21-day cycle.
paclitaxelDrug
Also called TAXOL®
80 mg/m^2 administered as IV infusion on Days 1, 8, and 15 of each 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab | Experimental | Participants receive 200 mg intravenous (IV) pembrolizumab on Day 1 of each 21-day cycle, for up to 35 administrations (approximately 2 years). Receives: Biological: pembrolizumab |
| Paclitaxel | Active comparator | 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. Receives: Drug: paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 30 months (through database cut-off date of 26 Oct 2017)
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.
Measured: Up to 30 months (through database cut-off date of 26 Oct 2017)
Secondary outcomes (22)
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.
Measured: Up to 30 months (through database cut-off date of 26 Oct 2017)
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.
Measured: Up to 30 months (through database cut-off date of 26 Oct 2017)
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.
Measured: Up to 30 months (through database cut-off date of 26 Oct 2017)
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.
Measured: Up to 30 months (through database cut-off date of 26 Oct 2017)
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.
Measured: Up to 30 months (through database cut-off date of 26 Oct 2017)
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.
Measured: Up to 30 months (through database cut-off date of 26 Oct 2017)
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.
Measured: Up to 30 months (through database cut-off date of 26 Oct 2017)
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.
Measured: Up to 30 months (through database cut-off date of 26 Oct 2017)
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.
Measured: Up to 30 months (through database cut-off date of 26 Oct 2017)
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.
Measured: Up to 30 months (through database cut-off date of 26 Oct 2017)
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.
Measured: Up to 30 months (through database cut-off date of 26 Oct 2017)
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.
Measured: Up to 30 months (through database cut-off date of 26 Oct 2017)
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.
Measured: Up to 30 months (through database cut-off date of 26 Oct 2017)
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.
Measured: Up to 30 months (through database cut-off date of 26 Oct 2017)
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.
Measured: Up to 30 months (through database cut-off date of 26 Oct 2017)
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.
Measured: Up to 30 months (through database cut-off date of 26 Oct 2017)
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.
Measured: Up to 30 months (through database cut-off date of 26 Oct 2017)
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.
Measured: Up to 30 months (through database cut-off date of 26 Oct 2017)
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.
Measured: Up to 71 months (through database cut-off date of 10 Jun 2021)
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.
Measured: Up to 71 months (through database cut-off date of 10 Jun 2021)
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.
Measured: Up to approximately 26.4 months
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.
Measured: Up to approximately 26.4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2015 (estimated)
- Study start11 May 2015
- Primary completion26 Oct 2017
- Study completion10 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Gastric AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 592 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02370498
- Sponsor's protocol ID
- 3475-061
- Other IDs
- 152988, MK-3475-061, 2014-005241-45, 2014
- Status last verified
- May 2022
- First submitted
- 23 Feb 2015
- Last updated
- 6 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
Janjigian YY, Cecchini M, Shitara K, Enzinger PC, Wainberg ZA, Chau I, Satoh T, Lee J, Nebozhyn M, Loboda A, Kobie J, Vajdi A, Shih CS, Cristescu R, Cao ZA. Genomic Landscape of Late-Stage Gastric Cancer: Analysis From KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 Studies. JCO Precis Oncol. 2025 Mar;9:e2400456. doi: 10.1200/PO-24-00456. Epub 2025 Mar 21.
PubMed 40117530Shitara K, Di Bartolomeo M, Mandala M, Ryu MH, Caglevic C, Olesinski T, Chung HC, Muro K, Goekkurt E, McDermott RS, Mansoor W, Wainberg ZA, Shih CS, Kobie J, Nebozhyn M, Cristescu R, Cao ZA, Loboda A, Ozguroglu M. Association between gene expression signatures and clinical outcomes of pembrolizumab versus paclitaxel in advanced gastric cancer: exploratory analysis from the randomized, controlled, phase III KEYNOTE-061 trial. J Immunother Cancer. 2023 Jun;11(6):e006920. doi: 10.1136/jitc-2023-006920.
PubMed 37399357Muro K, Shitara K, Yamaguchi K, Yoshikawa T, Satake H, Hara H, Sugimoto N, Machida N, Goto M, Kawakami H, Amagai K, Omuro Y, Esaki T, Hironaka S, Nishina T, Komatsu Y, Matsubara H, Shiratori S, Han S, Satoh T, Ohtsu A. Efficacy of Pembrolizumab Monotherapy in Japanese Patients with Advanced Gastric or Gastroesophageal Junction Cancer. J Gastrointest Cancer. 2023 Sep;54(3):951-961. doi: 10.1007/s12029-023-00920-9. Epub 2023 Apr 10.
PubMed 37037952Cristescu 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.
PubMed 35101941Fuchs 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.
PubMed 34468869Van 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.
PubMed 34363528Chao 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.
PubMed 33792646Shitara 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.
PubMed 29880231
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02370498
- Acronym / sponsor ID
- 3475-061
- Keywords
- Gastric cancer, Gastroesophageal junction cancer, PD1, PD-1, PDL1, PD-L1
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 592 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 11 May 2015 (actual)
- Primary completion
- 26 Oct 2017 (actual)
- Study completion
- 10 Jun 2021 (actual)
- First posted
- 25 Feb 2015 (estimated)
- Results
- Posted 20 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab | Experimental | Biological: pembrolizumabParticipants receive 200 mg intravenous (IV) pembrolizumab on Day 1 of each 21-day cycle, for up to 35 administrations (approximately 2 years). |
| Paclitaxel | Active comparator | Drug: paclitaxelParticipants receive 80 mg/m^2 IV paclitaxel on Days 1, 8, and 15 of each 28-day cycle, until disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| pembrolizumabAlso: MK-3475200 mg administered as IV infusion on Day 1 of each 21-day cycle. | Biological | Pembrolizumab |
| paclitaxelAlso: TAXOL®80 mg/m^2 administered as IV infusion on Days 1, 8, and 15 of each 28-day cycle. | Drug | Paclitaxel |
Primary outcome
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
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
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
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
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.
22 secondary outcomes
PFS According to RECIST 1.1 Based on BICR in All Participants
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
OS in All Participants
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
PFS According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
PFS According to RECIST 1.1 Based on Investigator Assessment in All Participants
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
PFS According to Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) Based on BICR in PD-L1 Positive Participants
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
PFS According to irRECIST Based on BICR in All Participants
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Time to Tumor Progression (TTP) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
TTP According to RECIST 1.1 Based on BICR in All Participants
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
TTP According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
TTP According to RECIST 1.1 Based on Investigator Assessment in All Participants
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Objective Response Rate (ORR) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
ORR According to RECIST 1.1 Based on BICR in All Participants
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
ORR According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
ORR According to RECIST 1.1 Based on Investigator Assessment in All Participants
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Duration of Response (DOR) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
DOR According to RECIST 1.1 Based on BICR in All Participants
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
DOR According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
DOR According to RECIST 1.1 Based on Investigator Assessment in All Participants
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Percentage of PD-L1 Positive Participants Who Experienced an Adverse Event (AE)
Time frame: Up to 71 months (through database cut-off date of 10 Jun 2021)
Percentage of All Participants Who Experienced an AE
Time frame: Up to 71 months (through database cut-off date of 10 Jun 2021)
Percentage of PD-L1 Positive Participants That Discontinued Study Treatment Due to AE
Time frame: Up to approximately 26.4 months
Percentage of All Participants That Discontinued Study Treatment Due to AE
Time frame: Up to approximately 26.4 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40117530Janjigian YY, Cecchini M, Shitara K, Enzinger PC, Wainberg ZA, Chau I, Satoh T, Lee J, Nebozhyn M, Loboda A, Kobie J, Vajdi A, Shih CS, Cristescu R, Cao ZA. Genomic Landscape of Late-Stage Gastric Cancer: Analysis From KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 Studies. JCO Precis Oncol. 2025 Mar;9:e2400456. doi: 10.1200/PO-24-00456. Epub 2025 Mar 21.
- Derived from this study: PubMed 37399357Shitara K, Di Bartolomeo M, Mandala M, Ryu MH, Caglevic C, Olesinski T, Chung HC, Muro K, Goekkurt E, McDermott RS, Mansoor W, Wainberg ZA, Shih CS, Kobie J, Nebozhyn M, Cristescu R, Cao ZA, Loboda A, Ozguroglu M. Association between gene expression signatures and clinical outcomes of pembrolizumab versus paclitaxel in advanced gastric cancer: exploratory analysis from the randomized, controlled, phase III KEYNOTE-061 trial. J Immunother Cancer. 2023 Jun;11(6):e006920. doi: 10.1136/jitc-2023-006920.
- Derived from this study: PubMed 37037952Muro K, Shitara K, Yamaguchi K, Yoshikawa T, Satake H, Hara H, Sugimoto N, Machida N, Goto M, Kawakami H, Amagai K, Omuro Y, Esaki T, Hironaka S, Nishina T, Komatsu Y, Matsubara H, Shiratori S, Han S, Satoh T, Ohtsu A. Efficacy of Pembrolizumab Monotherapy in Japanese Patients with Advanced Gastric or Gastroesophageal Junction Cancer. J Gastrointest Cancer. 2023 Sep;54(3):951-961. doi: 10.1007/s12029-023-00920-9. Epub 2023 Apr 10.
- Derived from this study: PubMed 35101941Cristescu 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.
- Derived from this study: PubMed 34468869Fuchs 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.
- Derived from this study: PubMed 34363528Van 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.
- Derived from this study: PubMed 33792646Chao 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.
- Derived from this study: PubMed 29880231Shitara 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.
- Merck Oncology Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing pembrolizumab and paclitaxel in people with Gastric Adenocarcinoma and Gastroesophageal Junction Adenocarcinoma, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02370498, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2022.