Clinical trial 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)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastric Cancer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-12-26
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: 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)
timeFrame: Up to ~36 months
Secondary outcomes:
measure: ORR According to Immune-related Response Evaluation Criteria In Solid Tumors (iRECIST) Assessed by BICR
timeFrame: Up to ~36 months
measure: Duration of Response (DOR) According to RECIST 1.1 Assessed by BICR
timeFrame: Up to ~36 months
measure: DOR According to iRECIST Assessed by BICR
timeFrame: Up to ~36 months
measure: Disease Control Rate (DCR) According to RECIST 1.1 Assessed by BICR
timeFrame: Up to ~36 months
measure: DCR According to iRECIST 1.1 Assessed by BICR
timeFrame: Up to ~36 months
measure: Time to Response (TTR) According to RECIST 1.1 Assessed by BICR
timeFrame: Up to ~36 months
measure: TTR According to iRECIST 1.1 Assessed by BICR
timeFrame: Up to ~36 months
measure: Progression-free Survival (PFS) According to RECIST 1.1 Assessed by BICR
timeFrame: Up to ~36 months
measure: PFS According to iRECIST 1.1 Assessed by BICR
timeFrame: Up to ~36 months
measure: Overall Survival (OS)
timeFrame: Up to ~36 months
measure: Number of Participants With ≥1 Adverse Event (AE)
timeFrame: Up to ~36 months
measure: Number of Participants Discontinuing From Study Treatment Due to AE(s)
timeFrame: Up to ~36 months
Other outcomes:
Locations:
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East ( Site 0001)
state: Chiba
city: Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center ( Site 0024)
state: Ehime
city: Ohta
country: Japan
facility: Gunma Prefectural Cancer Center ( Site 0005)
state: Gunma
city: Sapporo
country: Japan
facility: Hokkaido University Hospital ( Site 0006)
state: Hokkaido
city: Akashi
country: Japan
facility: Hyogo Cancer Center ( Site 0016)
state: Hyogo
city: Kobe
country: Japan
facility: Kobe City Medical Center General Hospital ( Site 0015)
state: Hyogo
city: Kasama
country: Japan
facility: Ibaraki Prefectural Central Hospital ( Site 0018)
state: Ibaraki
city: Sagamihara
country: Japan
facility: Kitasato University Hospital ( Site 0019)
state: Kanagawa
city: Yokohama
country: Japan
facility: Kanagawa Cancer Center ( Site 0003)
state: Kanagawa
city: Sendai
country: Japan
facility: Tohoku University Hospital ( Site 0023)
state: Miyagi
city: Osakasayama
country: Japan
facility: Kindai University Hospital ( Site 0013)
state: Osaka
city: Suita
country: Japan
facility: Osaka University Hospital ( Site 0010)
state: Osaka
city: Kitaadachi-gun
country: Japan
facility: Saitama Cancer Center ( Site 0004)
state: Saitama
city: Sunto-gun
country: Japan
facility: Shizuoka Cancer Center Hospital and Research Institute ( Site 0020)
state: Shizuoka
city: Shimotsuke
country: Japan
facility: Jichi Medical University Hospital ( Site 0009)
state: Tochigi
city: Chiba
country: Japan
facility: Chiba Cancer Center ( Site 0012)
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center ( Site 0017)
city: Fukuoka
country: Japan
facility: Kyushu University Hospital ( Site 0014)
city: Gifu
country: Japan
facility: Gifu University Hospital ( Site 0021)
city: Kochi
country: Japan
facility: Kochi Health Sciences Center ( Site 0022)
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital ( Site 0002)
city: Osaka
country: Japan
facility: Osaka International Cancer Institute ( Site 0011)
city: Tokyo
country: Japan
facility: National Cancer Center Hospital ( Site 0025)
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Komagome Hospital ( Site 0008)
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR ( Site 0007)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: https://pubmed.ncbi.nlm.nih.gov/35701865/
citation: 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.