Clinical trial NCT03019588: Efficacy and Safety Study of Pembrolizumab (MK-3475) Versus Paclitaxel in Asian Participants With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma Who Progressed After First-line Therapy With Platinum and Fluoropyrimidine (MK-3475-063/KEYNOTE-063)
Official title: A Phase III, Randomized, Open-label Clinical Trial of Pembrolizumab (MK-3475) Versus Paclitaxel in Asian Subjects With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma Who Progressed After First-Line Therapy With Platinum and Fluoropyrimidine
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Gastric Neoplasms
Gastroesophageal Junction Adenocarcinoma
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1)
Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-01-12
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study will compare the efficacy and safety of treatment with pembrolizumab (MK-3475) versus paclitaxel in Asian, programmed death-ligand 1 (PD-L1) positive participants with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma who have progressed after failure of any combination chemotherapy containing a platinum and a fluoropyrimidine agent.

The primary study hypotheses are that pembrolizumab prolongs Overall Survival (OS) compared to paclitaxel and that pembrolizumab prolongs Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) assessed by blinded central radiologists' review compared to paclitaxel.

Detailed description: Once the participant has achieved the study objective or the study has ended, the participant will be discontinued from the study and may be enrolled in an extension study to continue protocol-defined assessments and treatment. Enrollment in the extension study will be conditional on participant consent. Treatment with pembrolizumab or paclitaxel will continue until documented disease progression, unacceptable adverse event(s), intercurrent illness that prevents further administration of treatment, investigator's decision to discontinue the participant, participant withdraws consent, pregnancy of the participant, participant receives 35 administrations (approximately 2 years) of pembrolizumab, or administrative reasons requiring cessation of treatment.

Eligibility criteria: Inclusion Criteria:

* Has histologically or cytologically-confirmed diagnosis of gastric or GEJ adenocarcinoma.
* Has metastatic disease or locally advanced, unresectable disease.
* Has measurable disease as defined by RECIST 1.1 as determined by investigator.
* Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 3 days prior to the first dose of study treatment.
* Has experienced documented objective radiographic or clinical disease progression during or after first-line therapy containing any platinum/fluoropyrimidine doublet.
* Is willing to provide tissue for PD-L1 biomarker analysis.
* Has PD-L1 positive tumor (based on analysis of sample provided to core lab).
* Female participants of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study treatment for the pembrolizumab arm and through 180 days after the last dose of study treatment for the paclitaxel arm.
* Male participants should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study treatment for the pembrolizumab arm and through 180 days after the last dose of study treatment for the paclitaxel arm.
* Demonstrates adequate organ function.

Exclusion Criteria:

* Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of trial treatment.
* Has squamous cell or undifferentiated gastric cancer.
* Has active autoimmune disease that has required systemic treatment in past 2 years.
* Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the first dose of trial treatment or who has not recovered (i.e., ≤ Grade 1 or at Baseline) from AEs due to agents administered more than 4 weeks earlier.
* Has had prior chemotherapy, targeted small molecule therapy, radiation therapy, or any other agents used as systemic treatment for cancer, within 2 weeks prior to the first dose of trial treatment or who has not recovered (i.e., ≤ Grade 1 or at Baseline) from AEs due to a previously administered agent.
* Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
* Has an active infection requiring systemic therapy.
* 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 for the pembrolizumab arm and through 180 days after the last dose of study treatment for the paclitaxel arm.
* Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\], OX-40, CD137).
* Has a known history of Human Immunodeficiency Virus (HIV) infection.
* Has known active Hepatitis B or C virus infection.
* Has received a live vaccine within 30 days of planned start of study treatment.
* Has known allergy or hypersensitivity to paclitaxel or any components used in the paclitaxel preparation or other contraindication for taxane therapy.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 50 months
measure: Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to approximately 50 months
Secondary outcomes:
measure: Objective Response Rate (ORR) Per RECIST 1.1
timeFrame: Up to approximately 50 months
measure: Number of Participants Who Experience an Adverse Event (AE)
timeFrame: Up to approximately 50 months
measure: Number of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 25 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital ( Site 0022)
state: Beijing
city: Fuzhou
country: China
facility: Fuzhou General Hospital of Nanjing Military Command ( Site 0023)
state: Fujian
city: Changzhou
country: China
facility: The First People's Hospital of Changzhou ( Site 0024)
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing 81 PLA Hospital, Dept. of Oncology ( Site 0001)
state: Jiangsu
city: Changchun
country: China
facility: Jilin Province Cancer Hospital, Department of Chemotherapy ( Site 0002)
state: Jilin
city: XI An
country: China
facility: Tangdu Hospital ( Site 0030)
state: Shanxi
city: Hangzhou
country: China
facility: 2nd Affil Hosp of Zhejiang University College of Medicine ( Site 0014)
state: Zhejiang
city: Beijing
country: China
facility: 301 Hospital ( Site 0008)
city: Beijing
country: China
facility: 307 Hospital of PLA, Dept. of Oncology ( Site 0006)
city: Beijing
country: China
facility: Peking Union Medical College Hospital ( Site 0011)
city: Changsha
country: China
facility: Xiangya Hospital Central -South University ( Site 0021)
city: Hangzhou
country: China
facility: Sir Sun Sun Shaw Hosp, Zhejiang Univ,Oncology dept. ( Site 0016)
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University ( Site 0004)
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital ( Site 0020)
city: Hefei
country: China
facility: Anhui Provincial Hospital ( Site 0017)
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University ( Site 0012)
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University ( Site 0013)
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital ( Site 0003)
city: Shanghai
country: China
facility: Renji Hospital Shanghai Jiaotong University School of Medicine ( Site 0028)
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University ( Site 0018)
city: Shanghai
country: China
facility: Shanghai East Hospital ( Site 0033)
city: Shanghai
country: China
facility: Shanghai Tenth People's Hospital ( Site 0026)
city: Shanghai
country: China
facility: Zhongshan Hospital affiliated to Fudan University ( Site 0005)
city: Songjiang
country: China
facility: Shanghai First People's Hospital ( Site 0027)
city: Wuhan
country: China
facility: Tongji Medical College Huazhong Uinversity Of Science and Technology ( Site 0025)
city: Seongnam si
country: Korea, Republic of
facility: CHA Bundang Medical Center CHA University ( Site 0203)
state: Gyeonggi Do
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center ( Site 0202)
state: Gyeonggi-do
city: Suwon
country: Korea, Republic of
facility: The Catholic University of Korea, St. Vincent's Hospital ( Site 0201)
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center ( Site 0204)
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital ( Site 0205)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System ( Site 0206)
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre (UMMC) ( Site 0126)
state: Wilayah Persekutuan
city: Kaohsiung
country: Taiwan
facility: Chang Gung Medical Foundation - Kaohsiung ( Site 0227)
city: Taichung
country: Taiwan
facility: China Medical University Hospital. ( Site 0226)
city: Taipei
country: Taiwan
facility: Koo Foundation Sun Yat-Sen Cancer Center ( Site 0228)
city: Taipei
country: Taiwan
facility: MacKay Memorial Hospital ( Site 0229)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Chung HC, Kang YK, Chen Z, Bai Y, Wan Ishak WZ, Shim BY, Park YL, Koo DH, Lu J, Xu J, Chon HJ, Bai LY, Zeng S, Yuan Y, Chen YY, Gu K, Zhong WY, Kuang S, Shih CS, Qin SK. Pembrolizumab versus paclitaxel for previously treated advanced gastric or gastroesophageal junction cancer (KEYNOTE-063): A randomized, open-label, phase 3 trial in Asian patients. Cancer. 2022 Mar 1;128(5):995-1003. doi: 10.1002/cncr.34019. Epub 2021 Dec 8.