Gastric Neoplasms, Gastroesophageal Junction Adenocarcinoma
Conditions
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)
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.
Interventions
BIOLOGICALPembrolizumab
IV infusion
DRUGPaclitaxel
IV infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Per RECIST 1.1 | 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) | 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 | 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. |
Countries
China, Malaysia, South Korea, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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). | 47 |
| 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. | 47 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 44 | 46 |
| Overall Study | Study terminated by Sponsor | 3 | 1 |
Baseline characteristics
| Characteristic | Paclitaxel 80 mg/m^2 | Total | Pembrolizumab 200 mg |
|---|---|---|---|
| Age, Continuous | 59.0 years STANDARD_DEVIATION 11.2 | 58.5 years STANDARD_DEVIATION 10.8 | 58.0 years STANDARD_DEVIATION 10.4 |
| Eastern Cooperative Oncology Group Performance Status (ECOG PS) ECOG = 0 | 12 Participants | 26 Participants | 14 Participants |
| Eastern Cooperative Oncology Group Performance Status (ECOG PS) ECOG = 1 | 35 Participants | 68 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants | 94 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 47 Participants | 94 Participants | 47 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 10 Participants | 25 Participants | 15 Participants |
| Sex: Female, Male Male | 37 Participants | 69 Participants | 32 Participants |
| Time to progression on first-line therapy < 6 months | 30 Participants | 60 Participants | 30 Participants |
| Time to progression on first-line therapy >= 6 months | 17 Participants | 34 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 44 / 47 | 46 / 47 |
| other Total, other adverse events | 46 / 47 | 43 / 44 |
| serious Total, serious adverse events | 13 / 47 | 14 / 44 |
Outcome results
Primary
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.
Time frame: Up to approximately 50 months
Population: Analysis population includes all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab 200 mg | Overall Survival (OS) | 8.4 Months |
| Paclitaxel 80 mg/m^2 | Overall Survival (OS) | 7.7 Months |
p-value: 0.2995% CI: [0.58, 1.36]Log Rank
Primary
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.
Time frame: Up to approximately 50 months
Population: Analysis population includes all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab 200 mg | Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 1.9 Months |
| Paclitaxel 80 mg/m^2 | Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 4.0 Months |
p-value: 0.995495% CI: [1.14, 2.74]Log Rank
Secondary
Number of Participants Who Discontinue Study Treatment Due to an AE
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.
Time frame: Up to approximately 25 months
Population: Analysis population includes all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab 200 mg | Number of Participants Who Discontinue Study Treatment Due to an AE | 2 Participants |
| Paclitaxel 80 mg/m^2 | Number of Participants Who Discontinue Study Treatment Due to an AE | 7 Participants |
Secondary
Number of Participants Who Experience an Adverse Event (AE)
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.
Time frame: Up to approximately 50 months
Population: Analysis population includes all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab 200 mg | Number of Participants Who Experience an Adverse Event (AE) | 46 Participants |
| Paclitaxel 80 mg/m^2 | Number of Participants Who Experience an Adverse Event (AE) | 43 Participants |
Secondary
Objective Response Rate (ORR) Per RECIST 1.1
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.
Time frame: Up to approximately 50 months
Population: Analysis population includes all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab 200 mg | Objective Response Rate (ORR) Per RECIST 1.1 | 12.8 Percentage of participants |
| Paclitaxel 80 mg/m^2 | Objective Response Rate (ORR) Per RECIST 1.1 | 19.1 Percentage of participants |
p-value: 0.788495% CI: [-21.6, 9.3]Z-test