Study of Pembrolizumab (MK-3475) in Participants With Relapsed or Refractory Classical Hodgkin Lymphoma (MK-3475-087/KEYNOTE-087)

Merck Sharp & Dohme LLC211 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

211

Conditions

Hodgkin Lymphoma

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria: * Relapsed or refractory de novo classical Hodgkin lymphoma * Participant may have failed to achieve a response to, progressed after, or be ineligible for autologous stem cell transplant (auto-SCT) * Participant may have failed to achieve a response or progressed after treatment with brentuximab vedotin or may be brentuximab vedotin naïve * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Measurable disease * Adequate organ function Exclusion criteria: * Diagnosis of immunosuppression or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication * Prior monoclonal antibody within 4 weeks prior to study Day 1 or chemotherapy, targeted small molecular therapy, or radiation therapy within 2 weeks prior to study Day 1 * Prior allogeneic hematopoietic stem cell transplantation * Known clinically active central nervous system involvement * Known additional malignancy that is progressing or requires active treatment * Has a known history of Human Immunodeficiency Virus (HIV) * Has known active Hepatitis B (HBV) or Hepatitis C (HCV) * Active autoimmune disease requiring systemic treatment in past 2 years * Has a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis

Outcomes

Primary Outcomes

Overall Response Rate (ORR) by BICR Based on IWG Criteria

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.

Time frame: Up to approximately 99 months

Percentage of Participants Experiencing at Least One Adverse Event (AE)

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

Time frame: Up to 27 months

Percentage of Participants Discontinuing Study Drug Due to AEs

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

Time frame: Up to 24 months

Secondary Outcomes

Overall Response Rate (ORR) by BICR Based on Lugano Criteria

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.

Time frame: Up to approximately 99 months

Overall Response Rate (ORR) Assessed by Investigator Based on IWG Criteria

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.

Time frame: Up to approximately 99 months

Complete Remission Rate (CRR) by BICR Based on IWG Criteria

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.

Time frame: Up to approximately 99 months

Complete Remission Rate (CRR) by BICR Based on Lugano Criteria

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.

Time frame: Up to approximately 99 months

Complete Remission Rate (CRR) Assessed by Investigator Based on IWG Criteria

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.

Time frame: Up to approximately 99 months

Progression-free Survival (PFS) Based on BICR

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.

Time frame: Up to approximately 99 months

Progression-free Survival (PFS) Assessed by the Investigator

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.

Time frame: Up to approximately 99 months

Duration of Response (DOR) Based on BICR

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.

Time frame: Up to approximately 99 months

Duration of Response (DOR) Assessed by the Investigator

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.

Time frame: Up to approximately 99 months

Overall Survival (OS)

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.

Time frame: Up to approximately 99 months