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)

NCT ID: NCT03382600

Last Updated: 2024-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-26
• Study Completion Date: 2021-05-30

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.

Detailed Description

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).

Conditions

Gastric Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: BIOLOGICAL

200 mg Q3W on Day 1 by IV infusion

Oxaliplatin

Intervention Type: DRUG

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

TS-1

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: BIOLOGICAL

200 mg Q3W on Day 1 by IV infusion

TS-1

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

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

Interventions

Pembrolizumab

200 mg Q3W on Day 1 by IV infusion

Intervention Type: BIOLOGICAL

Oxaliplatin

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

Intervention Type: DRUG

TS-1

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

Intervention Type: DRUG

Cisplatin

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

Intervention Type: DRUG

Other Intervention Names

MK-3475

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

National Cancer Center Hospital East ( Site 0001)

Kashiwa, Chiba, Japan

National Hospital Organization Shikoku Cancer Center ( Site 0024)

Matsuyama, Ehime, Japan

Gunma Prefectural Cancer Center ( Site 0005)

Ohta, Gunma, Japan

Hokkaido University Hospital ( Site 0006)

Sapporo, Hokkaido, Japan

Hyogo Cancer Center ( Site 0016)

Akashi, Hyōgo, Japan

Kobe City Medical Center General Hospital ( Site 0015)

Kobe, Hyōgo, Japan

Ibaraki Prefectural Central Hospital ( Site 0018)

Kasama, Ibaraki, Japan

Kitasato University Hospital ( Site 0019)

Sagamihara, Kanagawa, Japan

Kanagawa Cancer Center ( Site 0003)

Yokohama, Kanagawa, Japan

Tohoku University Hospital ( Site 0023)

Sendai, Miyagi, Japan

Kindai University Hospital ( Site 0013)

Sayama, Osaka, Japan

Osaka University Hospital ( Site 0010)

Suita, Osaka, Japan

Saitama Cancer Center ( Site 0004)

Kitaadachi-gun, Saitama, Japan

Shizuoka Cancer Center Hospital and Research Institute ( Site 0020)

Sunto-gun, Shizuoka, Japan

Jichi Medical University Hospital ( Site 0009)

Shimotsuke, Tochigi, Japan

Chiba Cancer Center ( Site 0012)

Chiba, , Japan

National Hospital Organization Kyushu Cancer Center ( Site 0017)

Fukuoka, , Japan

Kyushu University Hospital ( Site 0014)

Fukuoka, , Japan

Gifu University Hospital ( Site 0021)

Gifu, , Japan

Kochi Health Sciences Center ( Site 0022)

Kochi, , Japan

Kumamoto University Hospital ( Site 0002)

Kumamoto, , Japan

Osaka International Cancer Institute ( Site 0011)

Osaka, , Japan

National Cancer Center Hospital ( Site 0025)

Tokyo, , Japan

Tokyo Metropolitan Komagome Hospital ( Site 0008)

Tokyo, , Japan

The Cancer Institute Hospital of JFCR ( Site 0007)

Tokyo, , Japan

Countries

Japan

References

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

Reference Type: 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.

Reference Type: DERIVED

PMID: 32145474 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://merckoncologyclinicaltrials.com

Merck Oncology Clinical Trials Information

Other Identifiers

MK-3475-659

Identifier Type: OTHER

Identifier Source: secondary_id

KEYNOTE-659

Identifier Type: OTHER

Identifier Source: secondary_id

3475-659

Identifier Type: -

Identifier Source: org_study_id