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)

NCT ID: NCT03019588

Last Updated: 2023-03-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-16
• Study Completion Date: 2021-06-29

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.

Conditions

Gastric Neoplasms; Gastroesophageal Junction Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pembrolizumab 200 mg

Participants receive pembrolizumab 200 mg intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: BIOLOGICAL

IV infusion

Paclitaxel 80 mg/m^2

Participants receive paclitaxel 80 mg/m\^2 IV infusion on Days 1, 8 and 15 of each 4-week cycle for up to approximately 2 years.

Group Type: ACTIVE_COMPARATOR

Paclitaxel

Intervention Type: DRUG

IV infusion

Interventions

Pembrolizumab

IV infusion

Intervention Type: BIOLOGICAL

Paclitaxel

IV infusion

Intervention Type: DRUG

Other Intervention Names

MK-3475

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.

• Minimum Eligible Age: 18 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

Beijing Cancer Hospital ( Site 0022)

Beijing, Beijing Municipality, China

Fuzhou General Hospital of Nanjing Military Command ( Site 0023)

Fuzhou, Fujian, China

The First People's Hospital of Changzhou ( Site 0024)

Changzhou, Jiangsu, China

Nanjing 81 PLA Hospital, Dept. of Oncology ( Site 0001)

Nanjing, Jiangsu, China

Jilin Province Cancer Hospital, Department of Chemotherapy ( Site 0002)

Changchun, Jilin, China

Tangdu Hospital ( Site 0030)

Xi’an, Shanxi, China

2nd Affil Hosp of Zhejiang University College of Medicine ( Site 0014)

Hangzhou, Zhejiang, China

301 Hospital ( Site 0008)

Beijing, , China

307 Hospital of PLA, Dept. of Oncology ( Site 0006)

Beijing, , China

Peking Union Medical College Hospital ( Site 0011)

Beijing, , China

Xiangya Hospital Central -South University ( Site 0021)

Changsha, , China

Sir Sun Sun Shaw Hosp, Zhejiang Univ,Oncology dept. ( Site 0016)

Hangzhou, , China

The First Affiliated Hospital of Zhejiang University ( Site 0004)

Hangzhou, , China

Harbin Medical University Cancer Hospital ( Site 0020)

Harbin, , China

Anhui Provincial Hospital ( Site 0017)

Hefei, , China

The First Affiliated Hospital of Anhui Medical University ( Site 0012)

Hefei, , China

The Second Hospital of Anhui Medical University ( Site 0013)

Hefei, , China

Jiangsu Cancer Hospital ( Site 0003)

Nanjing, , China

Renji Hospital Shanghai Jiaotong University School of Medicine ( Site 0028)

Shanghai, , China

Ruijin Hospital, Shanghai Jiaotong University ( Site 0018)

Shanghai, , China

Shanghai East Hospital ( Site 0033)

Shanghai, , China

Shanghai Tenth People's Hospital ( Site 0026)

Shanghai, , China

Zhongshan Hospital affiliated to Fudan University ( Site 0005)

Shanghai, , China

Shanghai First People's Hospital ( Site 0027)

Songjiang, , China

Tongji Medical College Huazhong Uinversity Of Science and Technology ( Site 0025)

Wuhan, , China

University Malaya Medical Centre (UMMC) ( Site 0126)

Kuala Lumpur, Kuala Lumpur, Malaysia

National Cancer Center ( Site 0202)

Goyang-si, Gyeonggi-do, South Korea

CHA Bundang Medical Center CHA University ( Site 0203)

Seongnam-si, Gyeonggi-do, South Korea

The Catholic University of Korea, St. Vincent's Hospital ( Site 0201)

Suwon, Gyeonggi-do, South Korea

Asan Medical Center ( Site 0204)

Seoul, , South Korea

Kangbuk Samsung Hospital ( Site 0205)

Seoul, , South Korea

Severance Hospital Yonsei University Health System ( Site 0206)

Seoul, , South Korea

Chang Gung Medical Foundation - Kaohsiung ( Site 0227)

Kaohsiung City, , Taiwan

China Medical University Hospital. ( Site 0226)

Taichung, , Taiwan

Koo Foundation Sun Yat-Sen Cancer Center ( Site 0228)

Taipei, , Taiwan

MacKay Memorial Hospital ( Site 0229)

Taipei, , Taiwan

Countries

China; Malaysia; South Korea; Taiwan

References

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.

Reference Type: DERIVED

PMID: 34878659 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://keynoteclinicaltrials.com/

Merck Oncology Clinical Trial Information

Other Identifiers

MK-3475-063

Identifier Type: OTHER

Identifier Source: secondary_id

3475-063

Identifier Type: -

Identifier Source: org_study_id