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)
Study Details
Study Description
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 |
|---|---|---|
|
Phase 3 |
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 Design
Arms and Interventions
| 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 Names:
|
| 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
|
Outcome Measures
Primary Outcome Measures
- Overall Survival (OS) [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.
- Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [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
- Objective Response Rate (ORR) per RECIST 1.1 [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.
- Number of Participants Who Experience an Adverse Event (AE) [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.
- Number of Participants Who Discontinue Study Treatment Due to an AE [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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Has histologically or cytologically-confirmed diagnosis of gastric or GEJ adenocarcinoma.
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Has metastatic disease or locally advanced, unresectable disease.
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Has measurable disease as defined by RECIST 1.1 as determined by investigator.
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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.
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Has experienced documented objective radiographic or clinical disease progression during or after first-line therapy containing any platinum/fluoropyrimidine doublet.
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Is willing to provide tissue for PD-L1 biomarker analysis.
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Has PD-L1 positive tumor (based on analysis of sample provided to core lab).
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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.
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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.
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Demonstrates adequate organ function.
Exclusion Criteria:
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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.
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Has squamous cell or undifferentiated gastric cancer.
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Has active autoimmune disease that has required systemic treatment in past 2 years.
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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.
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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.
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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.
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Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
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Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
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Has an active infection requiring systemic therapy.
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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.
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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).
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Has a known history of Human Immunodeficiency Virus (HIV) infection.
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Has known active Hepatitis B or C virus infection.
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Has received a live vaccine within 30 days of planned start of study treatment.
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Has known allergy or hypersensitivity to paclitaxel or any components used in the paclitaxel preparation or other contraindication for taxane therapy.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Cancer Hospital ( Site 0022) | Beijing | Beijing | China | |
| 2 | Fuzhou General Hospital of Nanjing Military Command ( Site 0023) | Fuzhou | Fujian | China | |
| 3 | The First People's Hospital of Changzhou ( Site 0024) | Changzhou | Jiangsu | China | |
| 4 | Nanjing 81 PLA Hospital, Dept. of Oncology ( Site 0001) | Nanjing | Jiangsu | China | |
| 5 | Jilin Province Cancer Hospital, Department of Chemotherapy ( Site 0002) | Changchun | Jilin | China | |
| 6 | Tangdu Hospital ( Site 0030) | XI An | Shanxi | China | |
| 7 | 2nd Affil Hosp of Zhejiang University College of Medicine ( Site 0014) | Hangzhou | Zhejiang | China | |
| 8 | 301 Hospital ( Site 0008) | Beijing | China | ||
| 9 | 307 Hospital of PLA, Dept. of Oncology ( Site 0006) | Beijing | China | ||
| 10 | Peking Union Medical College Hospital ( Site 0011) | Beijing | China | ||
| 11 | Xiangya Hospital Central -South University ( Site 0021) | Changsha | China | ||
| 12 | Sir Sun Sun Shaw Hosp, Zhejiang Univ,Oncology dept. ( Site 0016) | Hangzhou | China | ||
| 13 | The First Affiliated Hospital of Zhejiang University ( Site 0004) | Hangzhou | China | ||
| 14 | Harbin Medical University Cancer Hospital ( Site 0020) | Harbin | China | ||
| 15 | Anhui Provincial Hospital ( Site 0017) | Hefei | China | ||
| 16 | The First Affiliated Hospital of Anhui Medical University ( Site 0012) | Hefei | China | ||
| 17 | The Second Hospital of Anhui Medical University ( Site 0013) | Hefei | China | ||
| 18 | Jiangsu Cancer Hospital ( Site 0003) | Nanjing | China | ||
| 19 | Renji Hospital Shanghai Jiaotong University School of Medicine ( Site 0028) | Shanghai | China | ||
| 20 | Ruijin Hospital, Shanghai Jiaotong University ( Site 0018) | Shanghai | China | ||
| 21 | Shanghai East Hospital ( Site 0033) | Shanghai | China | ||
| 22 | Shanghai Tenth People's Hospital ( Site 0026) | Shanghai | China | ||
| 23 | Zhongshan Hospital affiliated to Fudan University ( Site 0005) | Shanghai | China | ||
| 24 | Shanghai First People's Hospital ( Site 0027) | Songjiang | China | ||
| 25 | Tongji Medical College Huazhong Uinversity Of Science and Technology ( Site 0025) | Wuhan | China | ||
| 26 | CHA Bundang Medical Center CHA University ( Site 0203) | Seongnam si | Gyeonggi Do | Korea, Republic of | 4130 |
| 27 | National Cancer Center ( Site 0202) | Goyang-si | Gyeonggi-do | Korea, Republic of | 4130 |
| 28 | The Catholic University of Korea, St. Vincent's Hospital ( Site 0201) | Suwon | Gyeonggi-do | Korea, Republic of | 4130 |
| 29 | Asan Medical Center ( Site 0204) | Seoul | Korea, Republic of | 4130 | |
| 30 | Kangbuk Samsung Hospital ( Site 0205) | Seoul | Korea, Republic of | 4130 | |
| 31 | Severance Hospital Yonsei University Health System ( Site 0206) | Seoul | Korea, Republic of | 4130 | |
| 32 | University Malaya Medical Centre (UMMC) ( Site 0126) | Kuala Lumpur | Wilayah Persekutuan | Malaysia | |
| 33 | Chang Gung Medical Foundation - Kaohsiung ( Site 0227) | Kaohsiung | Taiwan | ||
| 34 | China Medical University Hospital. ( Site 0226) | Taichung | Taiwan | ||
| 35 | Koo Foundation Sun Yat-Sen Cancer Center ( Site 0228) | Taipei | Taiwan | ||
| 36 | MacKay Memorial Hospital ( Site 0229) | Taipei | Taiwan |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 3475-063
- MK-3475-063