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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)

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ClinicalTrials.gov Identifier: NCT03019588
Recruitment Status : Recruiting
First Posted : January 12, 2017
Last Update Posted : January 24, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.


Condition or disease Intervention/treatment Phase
Gastric Neoplasms Gastroesophageal Junction Adenocarcinoma Biological: Pembrolizumab Drug: Paclitaxel Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 360 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 16, 2017
Estimated Primary Completion Date : August 17, 2019
Estimated Study Completion Date : June 29, 2020

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Pembrolizumab 200 mg
Participants receive pembrolizumab 200 mg intravenous (IV) infusion on Day 1 of each 3-week cycle for up to approximately 2 years.
Biological: Pembrolizumab
IV infusion
Other Name: MK-3475
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.
Drug: Paclitaxel
IV infusion



Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to 2 years ]
    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 will be censored at the date of the last follow-up.

  2. Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to 2 years ]
    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.


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) per RECIST 1.1 [ Time Frame: Up to 2 years ]
    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.

  2. Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to 27 months ]
    An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of study treatment, whether or not considered related to the use of study treatment.

  3. Number of Participants Who Discontinue Study Treatment Due to an AE [ Time Frame: Up to 2 years ]
    An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of study treatment, whether or not considered related to the use of study treatment.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 must 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03019588


Contacts
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

  Show 36 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Additional Information:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03019588     History of Changes
Other Study ID Numbers: 3475-063
MK-3475-063 ( Other Identifier: Merck Protocol Number )
First Posted: January 12, 2017    Key Record Dates
Last Update Posted: January 24, 2018
Last Verified: January 2018

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

Keywords provided by Merck Sharp & Dohme Corp.:
PD1
PD-1
PDL1
PD-L1

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Stomach Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Stomach Diseases
Paclitaxel
Pembrolizumab
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action