Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02684292




Registration number
NCT02684292
Ethics application status
Date submitted
12/02/2016
Date registered
17/02/2016
Date last updated
19/08/2022

Titles & IDs
Public title
Study of Pembrolizumab (MK-3475) vs. Brentuximab Vedotin in Participants With Relapsed or Refractory Classical Hodgkin Lymphoma (MK-3475-204/KEYNOTE-204)
Scientific title
A Phase III, Randomized, Open-label, Clinical Trial to Compare Pembrolizumab With Brentuximab Vedotin in Subjects With Relapsed or Refractory Classical Hodgkin Lymphoma
Secondary ID [1] 0 0
163337
Secondary ID [2] 0 0
3475-204
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hodgkin Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Hodgkin's

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - pembrolizumab
Other interventions - brentuximab vedotin

Experimental: Pembrolizumab - Participants receive pembrolizumab 200 mg administered intravenously (IV) on Day 1 of each 3-week cycle for up to 35 cycles.

Active Comparator: Brentuximab vedotin - Participants receive BV 1.8 mg/kg (maximum 180 mg per dose) IV on Day 1 of each 3-week cycle for up to 35 cycles.


Other interventions: pembrolizumab
IV infusion

Other interventions: brentuximab vedotin
IV infusion
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS)
Timepoint [1] 0 0
Up to approximately 40 months
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to approximately 40 months
Secondary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
Up to approximately 40 months

Eligibility
Key inclusion criteria
- Has relapsed (disease progression after most recent therapy) or refractory (failure to
achieve Complete Response [CR] or Partial Response [PR] to most recent therapy)
classical Hodgkin Lymphoma.

- Has responded (achieved a CR or PR) to BV or BV-containing regimens, if previously
treated with BV.

- Has measurable disease defined as =1 lesion that can be accurately measured in =2
dimensions with spiral computed tomography (CT) scan or combined CT/positron emission
tomography (PET) scan. Minimum measurement must be >15 mm in the longest diameter or
>10 mm in the short axis.

- Is able to provide an evaluable core or excisional lymph node biopsy for biomarker
analysis from an archival (>60 days) or newly obtained (within 60 days) biopsy at
Screening (Visit 1).

- Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
Performance Scale.

- Has adequate organ function

- Female participants of childbearing potential must be willing to use an adequate
method of contraception for the course of the study through 120 days (for participants
receiving pembrolizumab) or 180 days (for participants receiving BV) after the last
dose of study drug.

- Male participants of childbearing potential must be willing to use an adequate method
of contraception starting with the first dose of study drug through 120 days (for
participants receiving pembrolizumab) or 180 days (for participants receiving BV)
after the last dose of study drug.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Has hypersensitivity to the active substance or to any of the excipients in BV or
pembrolizumab.

- Is currently participating in or has participated in a study of an investigational
agent and is currently receiving study therapy or has participated in a study of an
investigational agent and has received study therapy or used an investigational device
within 4 weeks of the first dose of study drug.

- Has a diagnosis of immunosuppression or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of study
drug.

- Has had a prior monoclonal antibody (mAb) within 4 weeks prior to first dose of study
drug in the study or who has not recovered (i.e., = Grade 1 or at baseline) from
adverse events (AEs) due to agents administered more than 4 weeks earlier.

- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
including investigational agents within 4 weeks prior to study Day 1 or who has not
recovered (i.e., = Grade 1 or at baseline) from AEs due to a previously administered
agent.

- Has undergone prior allogeneic hematopoietic stem cell transplantation within the last
5 years. Note: Participants who have had a transplant greater than 5 years ago are
eligible as long as there are no symptoms of graft-versus-host disease (GVHD).

- Has a known additional malignancy that is progressing or requires active treatment in
the last 3 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. Participants with previously treated brain metastases may participate
provided they are radiologically stable (i.e., without evidence of progression by
repeat imaging), clinically stable and without requirement of steroid treatment for
=14 days prior to the first dose of study drug.

- Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e., with the use of disease modifying agents, corticosteroids, or immunosuppressive
drugs).

- Has a history of (non-infectious) pneumonitis that required steroids, or current
pneumonitis.

- Has an active infection requiring intravenous systemic therapy.

- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.

- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 120 days
(for participants receiving pembrolizumab) or 180 days (for participants receiving BV)
after the last dose of study drug.

- Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1),
anti-PD-ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137, or cytotoxic
T-lymphocyte-associated protein 4 (CTLA-4) antibody (including ipilimumab) or OX-40
(Tumor necrosis factor receptor superfamily, member 4 [TNFRSF4]), or any other
antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.

- Has a known history of human immunodeficiency virus (HIV)

- Has active hepatitis B (HBV) or hepatitis C (HCV).

- Has a known history of active tuberculosis (TB; Bacillus tuberculosis).

- Has received a live vaccine within 30 days prior to first dose of study drug.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/05/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
18/07/2025
Actual
Sample size
Target
Accrual to date
Final
304
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate pembrolizumab (MK-3475) in the treatment of
participants with relapsed or refractory Classical Hodgkin Lymphoma. Participants will be
randomized to receive either pembrolizumab or brentuximab vedotin (BV) for up to 35
three-week cycles of treatment.

The primary hypotheses of this study are that treatment with pembrolizumab prolongs
Progression-free Survival (PFS) and Overall Survival (OS) in participants with relapsed or
refractory Classical Hodgkin Lymphoma compared to treatment with BV.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02684292
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02684292