Hodgkin LymphomaPhase 3NCT02684292
Study of Pembrolizumab (MK-3475) vs. Brentuximab Vedotin in Participants With Relapsed or Refractory Classical Hodgkin Lymphoma (MK-3475-204/KEYNOTE-204)
A Phase 3 study testing pembrolizumab and brentuximab vedotin in people with Hodgkin Lymphoma, run by Merck Sharp & Dohme LLC.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hodgkin Lymphoma
- What is being tested?
- pembrolizumab and brentuximab vedotin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 304 participants
- Where
- No sites listed yet
- Study dates
- 23 May 2016to 14 Jan 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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.
About this study
Official title: A Phase III, Randomized, Open-label, Clinical Trial to Compare Pembrolizumab With Brentuximab Vedotin in Subjects With Relapsed or Refractory Classical Hodgkin Lymphoma
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.
- Conditions
- Hodgkin Lymphoma
- Being tested
- pembrolizumab, brentuximab vedotin
- Keywords
- Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
- Medical subject headings
- Hodgkin Disease, Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pembrolizumabBiological
Also called MK-3475, KEYTRUDA®
IV infusion
brentuximab vedotinBiological
Also called ADCETRIS®
IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab | Experimental | Participants receive pembrolizumab 200 mg administered intravenously (IV) on Day 1 of each 3-week cycle for up to 35 cycles. Receives: Biological: pembrolizumab |
| Brentuximab vedotin | Active comparator | 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. Receives: Biological: brentuximab vedotin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS)
Measured: Up to approximately 40 months
Overall Survival (OS)
Measured: Up to approximately 40 months
Secondary outcomes (1)
Objective Response Rate (ORR)
Measured: Up to approximately 40 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2016 (estimated)
- Study start23 May 2016
- Primary completion14 Jan 2026
- Study completion14 Jan 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 304 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02684292
- Sponsor's protocol ID
- 3475-204
- Other IDs
- 163337, MK-3475-204, KEYNOTE-204, 2022-500400-22-00, U1111-1275-8432, 2015-005053-12, 2015
- Status last verified
- Feb 2026
- First submitted
- 12 Feb 2016
- Last updated
- 18 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
Kuruvilla J, Modi D, Santoro A, Paszkiewicz-Kozik E, Gasiorowski R, Johnson NA, Fogliatto LM, Goncalves I, de Oliveira J, Buccheri V, Perini GF, Goldschmidt N, Kriachok I, Sekiguchi N, Lin J, Yusuf R, Marinello P, Zinzani PL. Pembrolizumab in relapsed or refractory Hodgkin lymphoma: a post hoc analysis of KEYNOTE-204 by prior lines of therapy. Leuk Lymphoma. 2025 Sep;66(9):1710-1719. doi: 10.1080/10428194.2025.2502805. Epub 2025 Jun 23.
PubMed 40548833Kuruvilla J, Ramchandren R, Santoro A, Paszkiewicz-Kozik E, Gasiorowski R, Johnson NA, Fogliatto LM, Goncalves I, de Oliveira JSR, Buccheri V, Perini GF, Goldschmidt N, Kriachok I, Dickinson M, Komarnicki M, McDonald A, Ozcan M, Sekiguchi N, Zhu Y, Nahar A, Marinello P, Zinzani PL; KEYNOTE-204 investigators. Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study. Lancet Oncol. 2021 Apr;22(4):512-524. doi: 10.1016/S1470-2045(21)00005-X. Epub 2021 Mar 12.
PubMed 33721562
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomized, Open-label, Clinical Trial to Compare Pembrolizumab With Brentuximab Vedotin in Subjects With Relapsed or Refractory Classical Hodgkin Lymphoma
- ClinicalTrials.gov ID
- NCT02684292
- Acronym / sponsor ID
- 3475-204
- Conditions
- Hodgkin Lymphoma
- Keywords
- Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 304 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 23 May 2016 (actual)
- Primary completion
- 14 Jan 2026 (actual)
- Study completion
- 14 Jan 2026 (actual)
- First posted
- 17 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab | Experimental | Biological: pembrolizumabParticipants receive pembrolizumab 200 mg administered intravenously (IV) on Day 1 of each 3-week cycle for up to 35 cycles. |
| Brentuximab vedotin | Active comparator | Biological: brentuximab vedotinParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| pembrolizumabAlso: MK-3475, KEYTRUDA®IV infusion | Biological | Pembrolizumab |
| brentuximab vedotinAlso: ADCETRIS®IV infusion | Biological | Brentuximab vedotin |
Primary outcome
Progression-free Survival (PFS)
Time frame: Up to approximately 40 months
Overall Survival (OS)
Time frame: Up to approximately 40 months
1 secondary outcome
Objective Response Rate (ORR)
Time frame: Up to approximately 40 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2026.
- Derived from this study: PubMed 40548833Kuruvilla J, Modi D, Santoro A, Paszkiewicz-Kozik E, Gasiorowski R, Johnson NA, Fogliatto LM, Goncalves I, de Oliveira J, Buccheri V, Perini GF, Goldschmidt N, Kriachok I, Sekiguchi N, Lin J, Yusuf R, Marinello P, Zinzani PL. Pembrolizumab in relapsed or refractory Hodgkin lymphoma: a post hoc analysis of KEYNOTE-204 by prior lines of therapy. Leuk Lymphoma. 2025 Sep;66(9):1710-1719. doi: 10.1080/10428194.2025.2502805. Epub 2025 Jun 23.
- Derived from this study: PubMed 33721562Kuruvilla J, Ramchandren R, Santoro A, Paszkiewicz-Kozik E, Gasiorowski R, Johnson NA, Fogliatto LM, Goncalves I, de Oliveira JSR, Buccheri V, Perini GF, Goldschmidt N, Kriachok I, Dickinson M, Komarnicki M, McDonald A, Ozcan M, Sekiguchi N, Zhu Y, Nahar A, Marinello P, Zinzani PL; KEYNOTE-204 investigators. Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study. Lancet Oncol. 2021 Apr;22(4):512-524. doi: 10.1016/S1470-2045(21)00005-X. Epub 2021 Mar 12.
- Merck Oncology Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing pembrolizumab and brentuximab vedotin in people with Hodgkin Lymphoma, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) (time frame: Up to approximately 40 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02684292, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2026.