NCT02453594 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2024-10-29

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Percentage of Participants Discontinuing Study Drug Due to AEs

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Progression-free Survival (PFS) Based on BICR

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outcome · POSTED

Progression-free Survival (PFS) Assessed by the Investigator

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outcome · POSTED

Duration of Response (DOR) Based on BICR

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outcome · POSTED

Duration of Response (DOR) Assessed by the Investigator

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outcome · POSTED

Overall Survival (OS)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Biological: pembrolizumab
label
Cohort 1
type
EXPERIMENTAL
description
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.
intervention Names
Biological: pembrolizumab
label
Cohort 2
type
EXPERIMENTAL
description
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.
intervention Names
Biological: pembrolizumab
label
Cohort 3
type
EXPERIMENTAL

interventions

arm Group Labels
Cohort 1
Cohort 2
Cohort 3
description
IV infusion
name
pembrolizumab
other Names
MK-3475
KEYTRUDA®
type
BIOLOGICAL

Study design

allocation

NON_RANDOMIZED

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 211
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Overall Response Rate (ORR) by BICR Based on IWG Criteria
time Frame
Up to approximately 99 months
description
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
measure
Percentage of Participants Experiencing at Least One Adverse Event (AE)
time Frame
Up to 27 months
description
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
measure
Percentage of Participants Discontinuing Study Drug Due to AEs
time Frame
Up to 24 months

secondary Outcomes

description
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.
measure
Overall Response Rate (ORR) by BICR Based on Lugano Criteria
time Frame
Up to approximately 99 months
description
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.
measure
Overall Response Rate (ORR) Assessed by Investigator Based on IWG Criteria
time Frame
Up to approximately 99 months
description
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.
measure
Complete Remission Rate (CRR) by BICR Based on IWG Criteria
time Frame
Up to approximately 99 months
description
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.
measure
Complete Remission Rate (CRR) by BICR Based on Lugano Criteria
time Frame
Up to approximately 99 months
description
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.
measure
Complete Remission Rate (CRR) Assessed by Investigator Based on IWG Criteria
time Frame
Up to approximately 99 months
description
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.
measure
Progression-free Survival (PFS) Based on BICR
time Frame
Up to approximately 99 months
description
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.
measure
Progression-free Survival (PFS) Assessed by the Investigator
time Frame
Up to approximately 99 months
description
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.
measure
Duration of Response (DOR) Based on BICR
time Frame
Up to approximately 99 months
description
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.
measure
Duration of Response (DOR) Assessed by the Investigator
time Frame
Up to approximately 99 months
description
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.
measure
Overall Survival (OS)
time Frame
Up to approximately 99 months

Full study description

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.

Source references

references

citation
Armand P, Zinzani PL, Lee HJ, Johnson NA, Brice P, Radford J, Ribrag V, Molin D, Vassilakopoulos TP, Tomita A, von Tresckow B, Shipp MA, Herrera AF, Lin J, Kim E, Chakraborty S, Marinello P, Moskowitz CH. Five-year follow-up of KEYNOTE-087: pembrolizumab monotherapy for relapsed/refractory classical Hodgkin lymphoma. Blood. 2023 Sep 7;142(10):878-886. doi: 10.1182/blood.2022019386.
pmid
37319435
type
RESULT
citation
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pmid
40668662
type
DERIVED
citation
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pmid
31409671
type
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citation
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pmid
31395089
type
DERIVED
citation
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pmid
31012356
type
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citation
Chen R, Zinzani PL, Fanale MA, Armand P, Johnson NA, Brice P, Radford J, Ribrag V, Molin D, Vassilakopoulos TP, Tomita A, von Tresckow B, Shipp MA, Zhang Y, Ricart AD, Balakumaran A, Moskowitz CH; KEYNOTE-087. Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. J Clin Oncol. 2017 Jul 1;35(19):2125-2132. doi: 10.1200/JCO.2016.72.1316. Epub 2017 Apr 25.
pmid
28441111
type
DERIVED