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)

NCT03382600 | Completed Phase 2 Results

• 3 other identifiers: 3475-659MK-3475-659KEYNOTE-659
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 25

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.

Conditions

Gastric Cancer

Outcome Measures

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)

  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.

  Up to ~36 months

Secondary Outcomes (12)

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

  Up to ~36 months

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

  Up to ~36 months

• DOR According to iRECIST Assessed by BICR

  Up to ~36 months

• Disease Control Rate (DCR) According to RECIST 1.1 Assessed by BICR

  Up to ~36 months

• DCR According to iRECIST 1.1 Assessed by BICR

  Up to ~36 months

Study Arms (2)

Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1)

EXPERIMENTAL

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.

Biological: Pembrolizumab; Drug: Oxaliplatin; Drug: TS-1

Pembrolizumab + Cisplatin +TS-1 (Cohort 2)

EXPERIMENTAL

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; Drug: TS-1; Drug: Cisplatin

Interventions

Pembrolizumab BIOLOGICAL

200 mg Q3W on Day 1 by IV infusion

Also known as: MK-3475

Pembrolizumab + Cisplatin +TS-1 (Cohort 2); Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1)

Oxaliplatin DRUG

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

Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1)

TS-1 DRUG

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

Pembrolizumab + Cisplatin +TS-1 (Cohort 2); Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1)

Cisplatin DRUG

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

Pembrolizumab + Cisplatin +TS-1 (Cohort 2)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (25)

National Cancer Center Hospital East ( Site 0001)

Kashiwa, Chiba, 277-8577, Japan

Location

National Hospital Organization Shikoku Cancer Center ( Site 0024)

Matsuyama, Ehime, 791-0280, Japan

Location

Gunma Prefectural Cancer Center ( Site 0005)

Ohta, Gunma, 373-8550, Japan

Location

Hokkaido University Hospital ( Site 0006)

Sapporo, Hokkaido, 060-8648, Japan

Location

Hyogo Cancer Center ( Site 0016)

Akashi, Hyōgo, 673-8558, Japan

Location

Kobe City Medical Center General Hospital ( Site 0015)

Kobe, Hyōgo, 650-0047, Japan

Location

Ibaraki Prefectural Central Hospital ( Site 0018)

Kasama, Ibaraki, 309-1793, Japan

Location

Kitasato University Hospital ( Site 0019)

Sagamihara, Kanagawa, 252-0375, Japan

Location

Kanagawa Cancer Center ( Site 0003)

Yokohama, Kanagawa, 241-8515, Japan

Location

Tohoku University Hospital ( Site 0023)

Sendai, Miyagi, 980-8574, Japan

Location

Kindai University Hospital ( Site 0013)

Sayama, Osaka, 589-8511, Japan

Location

Osaka University Hospital ( Site 0010)

Suita, Osaka, 565-0871, Japan

Location

Saitama Cancer Center ( Site 0004)

Kitaadachi-gun, Saitama, 362-0806, Japan

Location

Shizuoka Cancer Center Hospital and Research Institute ( Site 0020)

Sunto-gun, Shizuoka, 411-8777, Japan

Location

Jichi Medical University Hospital ( Site 0009)

Shimotsuke, Tochigi, 329-0498, Japan

Location

Chiba Cancer Center ( Site 0012)

Chiba, 260-8717, Japan

Location

National Hospital Organization Kyushu Cancer Center ( Site 0017)

Fukuoka, 811-1395, Japan

Location

Kyushu University Hospital ( Site 0014)

Fukuoka, 812-8582, Japan

Location

Gifu University Hospital ( Site 0021)

Gifu, 501-1194, Japan

Location

Kochi Health Sciences Center ( Site 0022)

Kochi, 781-8555, Japan

Location

Kumamoto University Hospital ( Site 0002)

Kumamoto, 860-8556, Japan

Location

Osaka International Cancer Institute ( Site 0011)

Osaka, 541-8567, Japan

Location

National Cancer Center Hospital ( Site 0025)

Tokyo, 104-0045, Japan

Location

Tokyo Metropolitan Komagome Hospital ( Site 0008)

Tokyo, 113-8677, Japan

Location

The Cancer Institute Hospital of JFCR ( Site 0007)

Tokyo, 135-8550, Japan

Location

Related Publications (2)

• https://pubmed.ncbi.nlm.nih.gov/35701865/

  RESULT

• Kawazoe A, Yamaguchi K, Yasui H, Negoro Y, Azuma M, Amagai K, Hara H, Baba H, Tsuda M, Hosaka H, Kawakami H, Oshima T, Omuro Y, Machida N, Esaki T, Yoshida K, Nishina T, Komatsu Y, Han SR, Shiratori S, Shitara K. Safety and efficacy of pembrolizumab in combination with S-1 plus oxaliplatin as a first-line treatment in patients with advanced gastric/gastroesophageal junction cancer: Cohort 1 data from the KEYNOTE-659 phase IIb study. Eur J Cancer. 2020 Apr;129:97-106. doi: 10.1016/j.ejca.2020.02.002. Epub 2020 Mar 4.

  PMID: 32145474 DERIVED

Related Links

• Merck Oncology Clinical Trials Information

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

pembrolizumab; Oxaliplatin; titanium silicide; Cisplatin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2017
• First Posted: December 26, 2017
• Study Start: March 26, 2018
• Primary Completion: May 30, 2021
• Study Completion: May 30, 2021
• Last Updated: June 11, 2024
• Results First Posted: December 1, 2023

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share

Locations

JP (25)