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)

NCT03019588 | Terminated Phase 3 Results DMC

• 2 other identifiers: 3475-063MK-3475-063
• Study Type: interventional
• Target: 94
• Locations: 4 countries
• Sites: 36

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.

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)

Outcome Measures

Primary Outcomes (2)

• Overall Survival (OS)

  OS is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up.

  Up to approximately 50 months

• Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  PFS is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. PFS as assessed by blinded independent central review will be presented.

  Up to approximately 50 months

Secondary Outcomes (3)

• Objective Response Rate (ORR) Per RECIST 1.1

  Up to approximately 50 months

• Number of Participants Who Experience an Adverse Event (AE)

  Up to approximately 50 months

• Number of Participants Who Discontinue Study Treatment Due to an AE

  Up to approximately 25 months

Study Arms (2)

Pembrolizumab 200 mg

EXPERIMENTAL

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).

Biological: Pembrolizumab

Paclitaxel 80 mg/m^2

ACTIVE COMPARATOR

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.

Drug: Paclitaxel

Interventions

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475

Pembrolizumab 200 mg

Paclitaxel DRUG

IV infusion

Paclitaxel 80 mg/m^2

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (36)

Beijing Cancer Hospital ( Site 0022)

Beijing, Beijing Municipality, China

Location

Fuzhou General Hospital of Nanjing Military Command ( Site 0023)

Fuzhou, Fujian, China

Location

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

Changzhou, Jiangsu, China

Location

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

Nanjing, Jiangsu, China

Location

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

Changchun, Jilin, China

Location

Tangdu Hospital ( Site 0030)

Xi’an, Shanxi, China

Location

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

Hangzhou, Zhejiang, China

Location

301 Hospital ( Site 0008)

Beijing, China

Location

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

Beijing, China

Location

Peking Union Medical College Hospital ( Site 0011)

Beijing, China

Location

Xiangya Hospital Central -South University ( Site 0021)

Changsha, China

Location

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

Hangzhou, China

Location

The First Affiliated Hospital of Zhejiang University ( Site 0004)

Hangzhou, China

Location

Harbin Medical University Cancer Hospital ( Site 0020)

Harbin, China

Location

Anhui Provincial Hospital ( Site 0017)

Hefei, China

Location

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

Hefei, China

Location

The Second Hospital of Anhui Medical University ( Site 0013)

Hefei, China

Location

Jiangsu Cancer Hospital ( Site 0003)

Nanjing, China

Location

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

Shanghai, China

Location

Ruijin Hospital, Shanghai Jiaotong University ( Site 0018)

Shanghai, China

Location

Shanghai East Hospital ( Site 0033)

Shanghai, China

Location

Shanghai Tenth People's Hospital ( Site 0026)

Shanghai, China

Location

Zhongshan Hospital affiliated to Fudan University ( Site 0005)

Shanghai, China

Location

Shanghai First People's Hospital ( Site 0027)

Songjiang, China

Location

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

Wuhan, China

Location

University Malaya Medical Centre (UMMC) ( Site 0126)

Kuala Lumpur, Kuala Lumpur, Malaysia

Location

National Cancer Center ( Site 0202)

Goyang-si, Gyeonggi-do, 4130, South Korea

Location

CHA Bundang Medical Center CHA University ( Site 0203)

Seongnam-si, Gyeonggi-do, 4130, South Korea

Location

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

Suwon, Gyeonggi-do, 4130, South Korea

Location

Asan Medical Center ( Site 0204)

Seoul, 4130, South Korea

Location

Kangbuk Samsung Hospital ( Site 0205)

Seoul, 4130, South Korea

Location

Severance Hospital Yonsei University Health System ( Site 0206)

Seoul, 4130, South Korea

Location

Chang Gung Medical Foundation - Kaohsiung ( Site 0227)

Kaohsiung City, Taiwan

Location

China Medical University Hospital. ( Site 0226)

Taichung, Taiwan

Location

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

Taipei, Taiwan

Location

MacKay Memorial Hospital ( Site 0229)

Taipei, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 34878659 DERIVED

Related Links

• Merck Oncology Clinical Trial Information

MeSH Terms

Conditions

Stomach Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Paclitaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

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 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2017
• First Posted: January 12, 2017
• Study Start: February 16, 2017
• Primary Completion: June 29, 2021
• Study Completion: June 29, 2021
• Last Updated: March 30, 2023
• Results First Posted: March 30, 2023

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share

Locations

TW (4); KR (6); MY (1); CN (25)