Study of Pembrolizumab (MK-3475) in Participants With Relapsed or Refractory Classical Hodgkin Lymphoma (MK-3475-087/KEYNOTE-087)
- Registration Number
- NCT02453594
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
This is a study of pembrolizumab (MK-3475) for participants with relapsed/refractory classical Hodgkin Lymphoma (RRcHL) who: 1) have failed to achieve a response or progressed after autologous stem cell transplant (auto-SCT) and have relapsed after treatment with or failed to respond to brentuximab vedotin (BV) post auto-SCT or 2) were unable to achieve a Complete Response (CR) or Partial Response (PR) to salvage chemotherapy and did not receive auto-SCT, but have relapsed after treatment with or failed to respond to BV or 3) have failed to achieve a response to or progressed after auto-SCT and have not received BV post auto-SCT.
The primary study hypothesis is that treatment with single agent pembrolizumab will result in a clinically meaningful overall response rate.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 211
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cohort 1 pembrolizumab Participants with RRcHL who failed to achieve a response or progressed after auto-SCT and have relapsed after treatment with or failed to respond to BV post auto-SCT received pembrolizumab, 200 mg, intravenously (IV) every 3 weeks (Q3W) on Day 1 of each 21-day cycle for up to 24 months. Cohort 2 pembrolizumab Participants with RRcHL who were unable to achieve CR or PR to salvage chemotherapy and did not receive auto-SCT, but have relapsed after treatment with or failed to respond to BV received pembrolizumab, 200 mg, IV Q3W on Day 1 of each 21-day cycle for up to 24 months. Cohort 3 pembrolizumab Participants with RRcHL who failed to achieve a response to or progressed after auto-SCT and have not received BV post auto-SCT received pembrolizumab, 200 mg, IV Q3W on Day 1 of each 21-day cycle for up to 24 months. These participants may or may not have received BV as part of primary treatment or salvage treatment.
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) by BICR Based on IWG Criteria Up to approximately 99 months ORR is the percentage of participants who had a complete response (CR) or partial response (PR) prior to disease progression based on the International Working Group (IWG) criteria using blinded independent central review (BICR). CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. The point estimate and 95% 2-sided exact confidence interval (CI) used the Clopper-Pearson method. An exact binomial test was conducted for each cohort versus a fixed control rate for each cohort. It is hypothesized that ORR will be greater than 20% in each of the 3 cohorts.
Percentage of Participants Experiencing at Least One Adverse Event (AE) Up to 27 months An adverse event (AE) is any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study
Percentage of Participants Discontinuing Study Drug Due to AEs Up to 24 months An AE is any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study
- Secondary Outcome Measures
Name Time Method Overall Response Rate (ORR) by BICR Based on Lugano Criteria Up to approximately 99 months ORR is the percentage of participants who had a CR or PR prior to disease progression based on the Lugano criteria using BICR. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. The point estimate and 95% 2-sided exact confidence interval (CI) used the Clopper-Pearson method. An exact binomial test was conducted for each cohort versus a fixed control rate for each cohort.
Progression-free Survival (PFS) Based on BICR Up to approximately 99 months PFS is the time from first dose to the first documented progressive disease (PD) or death due to any cause, whichever occurs first based on BICR. For those who have PD, the true date of disease progression was approximated by the date of the first assessment at which PD is objectively documented per IWG criteria, regardless of discontinuation of study drug. Death is always considered as a confirmed PD event. The non-parametric Kaplan-Meier method was used to estimate the PFS curve with missing data censored at last assessment.
Progression-free Survival (PFS) Assessed by the Investigator Up to approximately 99 months PFS is the time from first dose to the first documented progressive disease (PD) or death due to any cause, whichever occurs first assessed by the investigator based on the IWG criteria. For those who have PD, the true date of disease progression was approximated by the date of the first assessment at which PD is objectively documented per IWG criteria, regardless of discontinuation of study drug. Death is always considered as a confirmed PD event. The non-parametric Kaplan-Meier method was used to estimate the PFS curve with missing data censored at last assessment.
Duration of Response (DOR) Based on BICR Up to approximately 99 months DOR for the subgroup of participants who achieved a CR or PR by independent central review, is the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of PD or to death due to any cause, whichever comes first based on BICR. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. The analysis used the Kaplan-Meier method, with participants with response censored at their last assessment, and there was no progressive disease at the time of the last disease assessment.
Duration of Response (DOR) Assessed by the Investigator Up to approximately 99 months DOR for the subgroup of participants who achieved a CR or PR by independent central review, is the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of PD or to death due to any cause, whichever comes first assessed by the investigator based on the IWG criteria. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. The analysis used the Kaplan-Meier method, with participants with response censored at their last assessment, and there was no progressive disease at the time of the last disease assessment.
Overall Survival (OS) Up to approximately 99 months OS is the time from the first dose to death due to any cause. The Kaplan-Meier method was used to estimate the survival curve, separately by Cohort with missing data censored at last assessment.
Overall Response Rate (ORR) Assessed by Investigator Based on IWG Criteria Up to approximately 99 months ORR is the percentage of participants who had a CR or PR prior to disease progression assessed by the investigator using IWG criteria. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. The point estimate and 95% 2-sided exact confidence interval (CI) used the Clopper-Pearson method. An exact binomial test was conducted for each cohort versus a fixed control rate for each cohort.
Complete Remission Rate (CRR) by BICR Based on Lugano Criteria Up to approximately 99 months CRR is the percentage of participants with complete remission as demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes based on the Lugano criteria using BICR. The analysis consisted of the point estimate and 95% 2-sided exact CI, separately by Cohort using the Clopper-Pearson method. Additional analyses were based on site assessment and by central review using the Lugano (2014) criteria.
Complete Remission Rate (CRR) by BICR Based on IWG Criteria Up to approximately 99 months CRR is the percentage of participants with complete remission as demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes based on the IWG criteria using BICR. The analysis consisted of the point estimate and 95% 2-sided exact CI, separately by Cohort using the Clopper-Pearson method. Additional analyses were based on site assessment and by central review using the Lugano (2014) criteria.
Complete Remission Rate (CRR) Assessed by Investigator Based on IWG Criteria Up to approximately 99 months CRR is the percentage of participants with complete remission as demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes assessed by the investigator using IWG criteria. The analysis consisted of the point estimate and 95% 2-sided exact CI, separately by Cohort using the Clopper-Pearson method. Additional analyses were based on site assessment and by central review using the Lugano (2014) criteria.