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 |
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Recruitment Status :
Completed
First Posted : December 26, 2017
Results First Posted : December 1, 2023
Last Update Posted : December 29, 2023
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Sponsor:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC
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Brief Summary:
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Gastric Cancer | Biological: Pembrolizumab Drug: Oxaliplatin Drug: TS-1 Drug: Cisplatin | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 100 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential 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 |
| Actual Primary Completion Date : | May 30, 2021 |
| Actual Study Completion Date : | May 30, 2021 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Stomach Cancer
| Arm | Intervention/treatment |
|---|---|
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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, and will continue for up to ~3 years.
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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 |
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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, and will continue for up to ~3 years.
|
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 :
- 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 Outcome Measures :
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
- 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.
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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
Locations
Show 25 study locations
Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
| Study Director: | Medical Director | Merck Sharp & Dohme LLC |
Study Documents (Full-Text)
Documents provided by Merck Sharp & Dohme LLC:
Documents provided by Merck Sharp & Dohme LLC:
Study Protocol and Statistical Analysis Plan [PDF] November 27, 2017
Additional Information:
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications of Results:
Phase IIb study of pembrolizumab combined with S-1 + oxaliplatin or S-1 + cisplatin as first-line chemotherapy for gastric cancer - PubMed (nih.gov)
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Merck Sharp & Dohme LLC |
| ClinicalTrials.gov Identifier: | NCT03382600 |
| Other Study ID Numbers: |
3475-659 MK-3475-659 ( Other Identifier: Merck ) KEYNOTE-659 ( Other Identifier: Merck ) |
| First Posted: | December 26, 2017 Key Record Dates |
| Results First Posted: | December 1, 2023 |
| Last Update Posted: | December 29, 2023 |
| Last Verified: | December 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf |
| URL: | http://engagezone.msd.com/ds_documentation.php |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Stomach Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases |
Stomach Diseases Pembrolizumab Oxaliplatin Antineoplastic Agents Antineoplastic Agents, Immunological Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action |