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Completed

NCT Number: NCT03382600

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)

The purpose of this study is to estimate objective 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.

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Key information

Conditions

Gastric Cancer Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Neoplasms Neoplasms by Site Stomach Diseases Stomach Neoplasms

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

National Cancer Center Hospital East ( Site 0001), Kashiwa, Chiba, Japan

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About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Pembrolizumab

Biological

200 mg Q3W on Day 1 by IV infusion

Other names: MK-3475

Oxaliplatin

Drug

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

TS-1

Drug

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

Cisplatin

Drug

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

Primary outcomes

  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 ~36 months

    For the primary efficacy analysis, ORR was 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 SOD) per RECIST 1.1 as assessed by BICR.

Secondary outcomes

  1. ORR According to Immune-related Response Evaluation Criteria In Solid Tumors (iRECIST) Assessed by BICR

    Time frame: Up to ~36 months

    For the secondary efficacy analysis, ORR was defined as the percentage of participants whose best response based on imaging is CR (disappearance of all target lesions) or PR (≥30% decrease in the SOD of target lesions, taking as reference the baseline SOD) 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.

  2. Duration of Response (DOR) According to RECIST 1.1 Assessed by BICR

    Time frame: Up to ~36 months

    For participants who demonstrated complete response (CR, disappearance of all target lesions) or partial response (PR, ≥30% decrease in the SOD of target lesions) according to RECIST 1.1 as assessed by BICR, DOR was defined as the time from the earliest date of qualifying response (CR or PR) until earliest date of progressive disease (PD, ≥20% increase in the SOD of target lesions) or death from any cause, whichever came first. DOR was censored at the last tumor assessment date if a responder did not have PD or death.

  3. DOR According to iRECIST Assessed by BICR

    Time frame: Up to ~36 months

    For participants who demonstrated complete response (CR, disappearance of all target lesions) or partial response (PR, ≥30% decrease in the SOD of target lesions) according to iRECIST as assessed by BICR, DOR was defined as the time from the earliest date of qualifying response (CR or PR) until earliest date of progressive disease (PD, ≥20% increase in the SOD of target lesions) or death from any cause, whichever came first. DOR was censored at the last tumor assessment date if a responder did 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 ~36 months

    DCR was defined as the percentage of participants in the analysis population who have complete response (CR, disappearance of all target lesions), partial response (PR (≥30% decrease in the SOD of target lesions, taking as reference the baseline SOD), or stable disease (SD, neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD, ≥20% increase in the SOD of target lesions]). 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 ~36 months

    DCR was defined as the percentage of participants in the analysis population who have CR (disappearance of all target lesions), PR (≥30% decrease in the SOD of target lesions, taking as reference the baseline SOD), or stable disease (SD, neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD [≥20% increase in the SOD of target lesions]). 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 ~36 months

    TTR was defined as the time from the date of enrollment day to the first date of confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the SOD of target lesions, taking as reference the baseline SOD). 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 ~36 months

    TTR was defined as the time from the date of enrollment day to the first date of confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the SOD of target lesions, taking as reference the baseline SOD). 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 ~36 months

    PFS was defined as the time from the date of enrollment day to the first documented PD (defined as ≥20% increase in the SOD of target lesions) or death due to any cause, whichever occurred 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 ~36 months

    PFS was defined as the time from the date of enrollment day to the first documented PD (defined as ≥20% increase in the SOD of target lesions) or death due to any cause, whichever occurred 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 ~36 months

    OS was 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 were censored at the date of the last follow-up. For these participants, date of last follow up was last visit date instead of death date.

  11. Number of Participants With ≥1 Adverse Event (AE)

    Time frame: Up to ~36 months

    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. Number of Participants Discontinuing From Study Treatment Due to AE(s)

    Time frame: Up to ~36 months

    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.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study 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)

Important dates

Study start
2018
Primary completion
2021
Study completion
2021
First posted
Dec 26, 2017
Registry last updated
Jun 11, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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