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)

• ClinicalTrials.gov Identifier: NCT03019588
• Recruitment Status: Terminated
• First Posted: January 12, 2017
• Results First Posted: March 30, 2023
• Last Update Posted: March 30, 2023
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: January 11, 2017
• First Posted Date: January 12, 2017
• Results First Submitted Date: June 21, 2022
• Results First Posted Date: March 30, 2023
• Last Update Posted Date: March 30, 2023
• Actual Study Start Date: February 16, 2017
• Actual Primary Completion Date: June 29, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 21, 2022)

• Overall Survival (OS) [ Time Frame: Up to approximately 50 months ]
  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.
• Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to approximately 50 months ]
  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.

Original Primary Outcome Measures (submitted: January 11, 2017)

• OS [ Time Frame: Up to 2 years ]
• PFS [ Time Frame: Up to 2 years ]

Current Secondary Outcome Measures (submitted: June 21, 2022)

• Objective Response Rate (ORR) Per RECIST 1.1 [ Time Frame: Up to approximately 50 months ]
  ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1.
• Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 50 months ]
  An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
• Number of Participants Who Discontinue Study Treatment Due to an AE [ Time Frame: Up to approximately 25 months ]
  An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Original Secondary Outcome Measures (submitted: January 11, 2017)

• Objective Response Rate (ORR) per RECIST 1.1 [ Time Frame: Up to 2 years ]
• Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to 27 months ]
• Number of Participants Who Discontinue Study Treatment Due to an AE [ Time Frame: Up to 2 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Gastric Neoplasms
• Gastroesophageal Junction Adenocarcinoma

Intervention

• Biological: Pembrolizumab
  IV infusion
  Other Name: MK-3475
• Drug: Paclitaxel
  IV infusion

Study Arms

• Experimental: 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).
  Intervention: Biological: Pembrolizumab
• Active Comparator: 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.
  Intervention: Drug: Paclitaxel

• Publications *: 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: April 1, 2022): 94
• Original Estimated Enrollment (submitted: January 11, 2017): 360
• Actual Study Completion Date: June 29, 2021
• Actual Primary Completion Date: June 29, 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China, Korea, Republic of, Malaysia, Taiwan

Administrative Information

• NCT Number: NCT03019588
• Other Study ID Numbers: 3475-063; MK-3475-063 ( Other Identifier: Merck Protocol Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: June 2022