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Safety and Efficacy of Pembrolizumab (MK-3475) in Combination With TS-1+Cisplatin or TS-1+Oxaliplatin as First Line Chemotherapy in Gastric Cancer (MK-3475-659/KEYNOTE-659)

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ClinicalTrials.gov Identifier: NCT03382600
Recruitment Status : Recruiting
First Posted : December 26, 2017
Last Update Posted : July 25, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
The purpose of this study is to estimate overall response rates (ORRs) of pembrolizumab + oxaliplatin + TS-1 and pembrolizumab + cisplatin + TS-1, as first-line treatment for gastric cancer in programmed death-ligand 1 (PD-L1) positive, human epidermal growth factor receptor 2 (HER2/neu)-negative participants with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Condition or disease Intervention/treatment Phase
Gastric Cancer Biological: Pembrolizumab Drug: Oxaliplatin Drug: TS-1 Drug: Cisplatin Phase 2

Detailed Description:
Approximately 45 participants will be assigned first to pembrolizumab + oxaliplatin + TS-1 combination therapy (Cohort 1), and then 45 participants will be assigned to pembrolizumab + cisplatin + TS-1 combination therapy (Cohort 2).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase IIb, Clinical Trial to Study the Safety and Efficacy of Pembrolizumab (MK-3475) in Combination With TS-1+Cisplatin or TS-1+Oxaliplatin as a First Line Chemotherapy in Participants With Advanced or Recurrent Gastric Cancer (KEYNOTE-659)
Actual Study Start Date : March 26, 2018
Estimated Primary Completion Date : August 17, 2020
Estimated Study Completion Date : August 17, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Stomach Cancer

Arm Intervention/treatment
Experimental: Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1)
Participants receive Pembrolizumab 200 mg every 3 weeks (Q3W) plus oxaliplatin 130 mg/m^2 Q3W by intravenous (IV) infusion plus TS-1 twice daily (BID) by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment will be started on Day 1 of each 3-week course.
Biological: Pembrolizumab
200 mg Q3W on Day 1 by IV infusion
Other Name: MK-3475

Drug: Oxaliplatin
130 mg/m^2 Q3W on Day 1 by IV infusion

Drug: TS-1
40 to 60 mg orally according to Body Surface Area (BSA) BID Q3W on Days 1-14

Experimental: Pembrolizumab + Cisplatin +TS-1 (Cohort 2)
Participants receive Pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment will be started on Day 1 of each 3-week course.
Biological: Pembrolizumab
200 mg Q3W on Day 1 by IV infusion
Other Name: MK-3475

Drug: TS-1
40 to 60 mg orally according to Body Surface Area (BSA) BID Q3W on Days 1-14

Drug: Cisplatin
60 mg/m^2 Q3W on Day 1 by IV infusion




Primary Outcome Measures :
  1. Objective response rate (ORR) according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to ~2 years ]
    For the primary efficacy analysis, ORR is defined as the percentage of participants who have a best response of Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters [SOD] of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1 as assessed by BICR.


Secondary Outcome Measures :
  1. ORR according to immune-related Response Evaluation Criteria In Solid Tumors (iRECIST) assessed by BICR [ Time Frame: Up to ~2 years ]
    For the secondary efficacy analysis, ORR is defined as the percentage of participants whose best response based on imaging is CR (disappearance of all lesions) or PR (≥30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters) according to iRECIST as assessed by BICR. iRECIST is a modification to RECIST that takes into account unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression. At initial Progressive Disease (PD) by RECIST 1.1, if participant is clinically stable the investigator may continue to treat and scan again 4-8 weeks later to see if PD confirmed by iRECIST criteria.

  2. Duration of Response (DOR) according to RECIST 1.1 assessed by BICR [ Time Frame: Up to ~2 years ]
    For participants who demonstrate CR or PR according to RECIST 1.1 as assessed by BICR, DOR is defined as the time from the earliest date of qualifying response (CR or PR) until earliest date of disease progression or death from any cause, whichever comes first. DOR will be censored at the last tumor assessment date if a responder does not have PD or death.

  3. DOR according to iRECIST assessed by BICR [ Time Frame: Up to ~2 years ]
    For participants who demonstrate CR or PR according to iRECIST as assessed by BICR, DOR is defined as the time from the earliest date of qualifying response (CR or PR) until earliest date of disease progression or death from any cause, whichever comes first. DOR will be censored at the last tumor assessment date if a responder does not have PD or death. iRECIST is a modification to RECIST that takes into account unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression.

  4. Disease Control Rate (DCR) according to RECIST 1.1 assessed by BICR [ Time Frame: Up to ~2 years ]
    DCR is defined as the percentage of participants in the analysis population who have CR (disappearance of all lesions), PR (≥30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters), or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD). Responses are according to RECIST 1.1 as assessed by BICR.

  5. DCR according to iRECIST 1.1 assessed by BICR [ Time Frame: Up to ~2 years ]
    DCR is defined as the percentage of participants in the analysis population who have CR (disappearance of all lesions), PR (≥30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters), or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD). Responses are according to iRECIST 1.1 as assessed by BICR. iRECIST is a modification to RECIST that takes into account unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression.

  6. Time to Response (TTR) according to RECIST 1.1 assessed by BICR [ Time Frame: Up to ~2 years ]
    TTR is defined as the time from the date of enrollment day to the first date of confirmed CR (disappearance of all lesions) or PR (≥30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters). Responses are according to RECIST 1.1 as assessed by BICR.

  7. TTR according to iRECIST 1.1 assessed by BICR [ Time Frame: Up to ~2 years ]
    TTR is defined as the time from the date of enrollment day to the first date of confirmed CR (disappearance of all lesions) or PR (≥30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters). Responses are according to iRECIST 1.1 as assessed by BICR. iRECIST is a modification to RECIST that takes into account unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression.

  8. Progression-free Survival (PFS) according to RECIST 1.1 assessed by BICR [ Time Frame: Up to ~2 years ]
    PFS is defined as the time from the date of enrollment day to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 as assessed by BICR.

  9. PFS according to iRECIST 1.1 assessed by BICR [ Time Frame: Up to ~2 years ]
    PFS is defined as the time from the date of enrollment day to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to iRECIST 1.1 as assessed by BICR. iRECIST is a modification to RECIST that takes into account unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression.

  10. Overall survival (OS) [ Time Frame: Up to ~2 years ]
    OS is defined as the time from the date of enrollment day to death due to any cause. Participants without documented death at the time of the final analysis will be censored at the date of the last follow-up.

  11. Adverse events (AEs) [ Time Frame: From time of allocation up to 30 days following cessation of study treatment (up to ~2 years) ]
    The number of participants that experience an AE will be reported for each arm. An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment

  12. Treatment discontinuations due to AEs [ Time Frame: From time of allocation up to 30 days following cessation of study treatment (up to ~2 years) ]
    The number of participants that discontinue study drug due to an AE will be reported for each arm. An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Has histologically- or cytologically-confirmed diagnosis of locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma
  • Has a PD-L1 positive tumor as determined by immunohistochemistry (IHC) at a central laboratory
  • Has measurable disease as defined by RECIST 1.1 as determined by investigator assessment. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
  • Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test at the timing of enrollment
  • Participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication
  • Has adequate organ function

Exclusion Criteria:

  • Has squamous cell or undifferentiated gastric cancer
  • HER2-positive status
  • Has had previous therapy for locally advanced, unresectable or metastatic gastric/GEJ cancer
  • A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation
  • Has received prior therapy with a platinum-based anti-cancer drug
  • Has had major surgery, open biopsy or significant traumatic injury within 28 days prior to enrollment, or anticipation of the need for major surgery during the course of study treatment
  • Has had radiotherapy within 14 days of enrollment
  • Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
  • Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years with use of disease modifying agents, corticosteroids, or immunosuppressive drugs
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
  • Has any active infection requiring systemic therapy
  • Will be on flucytosine at the time of enrollment
  • Has grade ≥ 2 peripheral sensory neuropathy
  • Has poorly controlled diarrhea (e.g., watery stool, uncontrollable bowel movement with drugs, grade ≥ 2 and number of defecations, ≥ 5/day)
  • Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage within 2 weeks prior to enrollment
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with participation for the full duration of the trial, or is not in the best interest of the participant, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
  • Has received prior therapy with an anti-programmed death (PD)-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
  • Has known history of human immunodeficiency virus (HIV) [HIV1/2 antibodies]
  • Has a known history of Hepatitis B
  • Has received live vaccine within 30 days of the planned start of study therapy
  • Is currently participating in and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of trial treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03382600


Contacts
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
Japan
National Cancer Center Hospital East ( Site 0001) Recruiting
Kashiwa, Chiba, Japan, 277-8577
Contact: Study Coordinator    +81471331111      
National Hospital Organization Shikoku Cancer Center ( Site 0024) Recruiting
Matsuyama, Ehime, Japan, 791-0280
Contact: Study Coordinator    +81899991111      
Gunma Prefectural Cancer Center ( Site 0005) Recruiting
Ohta, Gunma, Japan, 373-8550
Contact: Study Coordinator    +81276380771      
Hokkaido University Hospital ( Site 0006) Recruiting
Sapporo, Hokkaido, Japan, 060-8648
Contact: Study Coordinator    +81117161161      
Hyogo Cancer Center ( Site 0016) Recruiting
Akashi, Hyogo, Japan, 673-8558
Contact: Study Coordinator    +81789291151      
Kobe City Medical Center General Hospital ( Site 0015) Recruiting
Kobe, Hyogo, Japan, 650-0047
Contact: Study Coordinator    +81783024321      
Ibaraki Prefectural Central Hospital ( Site 0018) Recruiting
Kasama, Ibaraki, Japan, 309-1793
Contact: Study Coordinator    +81296771121      
Kitasato University Hospital ( Site 0019) Recruiting
Sagamihara, Kanagawa, Japan, 252-0375
Contact: Study Coordinator    +81427788111      
Kanagawa Cancer Center ( Site 0003) Recruiting
Yokohama, Kanagawa, Japan, 241-8515
Contact: Study Coordinator    +81455202222      
Tohoku University Hospital ( Site 0023) Recruiting
Sendai, Miyagi, Japan, 980-8574
Contact: Study Coordinator    +81227177000      
Kindai University Hospital ( Site 0013) Recruiting
Osakasayama, Osaka, Japan, 589-8511
Contact: Study Coordinator    +81723660221      
Osaka University Hospital ( Site 0010) Recruiting
Suita, Osaka, Japan, 565-0871
Contact: Study Coordinator    +81668795111      
Saitama Cancer Center ( Site 0004) Recruiting
Kitaadachi-gun, Saitama, Japan, 362-0806
Contact: Study Coordinator    +81487221111      
Shizuoka Cancer Center Hospital and Research Institute ( Site 0020) Recruiting
Sunto-gun, Shizuoka, Japan, 411-8777
Contact: Study Coordinator    +81559895222      
Chiba Cancer Center ( Site 0012) Recruiting
Chiba, Japan, 260-8717
Contact: Study Coordinator    +81432645431      
National Hospital Organization Kyushu Cancer Center ( Site 0017) Recruiting
Fukuoka, Japan, 811-1395
Contact: Study Coordinator    +81925413231      
Kyushu University Hospital ( Site 0014) Recruiting
Fukuoka, Japan, 812-8582
Contact: Study Coordinator    +81926411151      
Gifu University Hospital ( Site 0021) Recruiting
Gifu, Japan, 501-1194
Contact: Study Coordinator    +81582306000      
Kochi Health Sciences Center ( Site 0022) Recruiting
Kochi, Japan, 781-8555
Contact: Study Coordinator    +81888373000      
Kumamoto University Hospital ( Site 0002) Recruiting
Kumamoto, Japan, 860-8556
Contact: Study Coordinator    +81963442111      
Osaka International Cancer Institute ( Site 0011) Recruiting
Osaka, Japan, 541-8567
Contact: Study Coordinator    +81669451181      
National Cancer Center Hospital ( Site 0025) Recruiting
Tokyo, Japan, 104-0045
Contact: Study Coordinator    +81335422511      
Tokyo Metropolitan Komagome Hospital ( Site 0008) Recruiting
Tokyo, Japan, 113-8677
Contact: Study Coordinator    +81338232101      
The Cancer Institute Hospital of JFCR ( Site 0007) Recruiting
Tokyo, Japan, 135-8550
Contact: Study Coordinator    +81335200111      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03382600     History of Changes
Other Study ID Numbers: 3475-659
First Posted: December 26, 2017    Key Record Dates
Last Update Posted: July 25, 2018
Last Verified: July 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Oxaliplatin
Pembrolizumab
Cisplatin
Antineoplastic Agents