Pembrolizumab and Brentuximab Vedotin in Subjects With Relapsed/Refractory T-cell Lymphoma

June 9, 2026 updated by: Tarsheen Sethi, Yale University

Phase 2 Study of Pembrolizumab and Brentuximab Vedotin in Subjects With Relapsed/Refractory CD30 Positive T-cell Lymphoma

This is a single arm, open label, multicenter study phase 2 study of pembrolizumab and brentuximab in subjects with relapsed/refractory CD30 positive T-cell lymphoma (including peripheral T-cell lymphoma and cutaneous T-cell lymphoma) who have received at least one prior therapy. We hypothesize that this combination is effective and will produce an overall response rate of ~55%. Pembrolizumab and brentuximab will be administered for 16 cycles in subjects with responsive disease. Pembrolizumab will be continued for an additional 19 cycles (total 35 cycles). Response assessments will occur at pre-specified intervals. For the primary endpoint the response assessment after 3 cycles will be taken into consideration. Dose adjustments for specific toxicities with either drug are detailed in the protocol. Based on statistical analysis 32 subjects will need to be accrued to evaluate for disease response based on historical control.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

CD30- Positive Peripheral T cell (PTCL) and Cutaneous T cell Lymphomas (CTCL):

T-cell Non-Hodgkin Lymphoma (NHL) includes a clinically heterogeneous group of mature T-cell lymphomas accounting for 10-12% of all NHL. Peripheral T- cell Lymphoma (PTCL) present with clinically aggressive disease with a poor outcome [with the exception of ALK+ Anaplastic Large Cell Lymphomas (ALCL)] and patients experience a high incidence of relapsed/ refractory disease that poses a therapeutic challenge. Despite progress in the past decade in understanding the biology of T-cell lymphomas, with the use of next generation sequencing and molecular profiling of archived tissue samples, there is yet an unmet need in therapeutic options. Amidst the wide range of T-cell lymphoma histologies, PTCL NOS is the most common histological subtype followed by ALCL, angioimmunoblastic lymphoma (AITL) and cutaneous T-cell lymphoma (CTCL). The other histological subtypes (Enteropathy associated T-cell Lymphoma, hepatosplenic T cell lymphoma, NK/T cell lymphoma etc.) account for <5% of T-cell subtypes. Unfortunately, the rare subtypes of T-cell Lymphoma are usually excluded from later phase trials due to their dismal prognosis.

Therapeutic Challenge in Relapsed/ Refractory PTCL and CTCL:

For patients with disease relapse following upfront chemotherapy, stem cell transplantation (SCT) is an option. However, this type of aggressive approach is only feasible in a minority of patients. Despite the advances in the therapeutic arsenal, most of these agents have a modest response rate of 20-30%. More than half of these patients who do respond initially, will ultimately relapse. Conventional chemotherapy in combination with novel agents has been under clinical evaluation with minor improvements in response rates compared with historical controls. Therefore, the urge to optimize therapy by incorporating newer treatments such as novel agents that have a more targeted approach continues to be critically important.

CTCL presents as a chronic disease with a poor prognosis in advanced stage disease. While recently approved agents have expanded the treatment repertoire for CTCL, there is still a need for additional agents as median response with current options averaging about a year(1).

In this context, the efficacy of the novel combination of CD30 directed antibody Brentuximab and PD-1 inhibitor Pembrolizumab in PTCL and CTCL is not known.

Study Type

Interventional

Enrollment (Estimated)

32

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Recruiting
        • Yale Smilow Cancer Hospital
        • Principal Investigator:
          • Tarsheen Sethi, MD
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Dana Farber Cancer Institute
        • Contact:
        • Sub-Investigator:
          • David Fisher, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of T-cell Non-Hodgkin lymphoma (T-NHL) will be enrolled in this study.
  2. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

  4. Histologically confirmed T-cell Non-Hodgkin lymphoma (T-NHL), including:

    • Peripheral T-cell lymphoma not other specified (PTCL nos)
    • Angioimmunoblastic T-cell lymphoma (AITL)
    • Anaplastic large-cell lymphoma (ALCL)
    • Natural killer (NK)/T-cell lymphoma (nodal or extranodal)
    • Cutaneous T-cell lymphoma (CTCL), including mycosis fungoides (MF)/sezary syndrome
    • Transformed T-cell lymphoma
    • Enteropathy-associated T-cell lymphoma (EATL);
    • Subcutaneous panniculitis-like T-cell lymphoma (SCPTCL)
    • Hepatosplenic T- cell lymphomas.
  5. Presence of CD30 (>1%) by IHC on a previous biopsy sample
  6. Relapsed/refractory disease having failed at least one prior systemic therapy Note: Single agent Brentuximab could have been a prior line of therapy EXCEPT those with ≥ grade 2 side effects leading to treatment discontinuation or those refractory to Brentuximab
  7. For patients with peripheral T-cell lymphoma (PTCL): At least one measurable target lesion ≥1.5 cm

  8. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

    • Not a woman of childbearing potential (WOCBP)
    • A woman of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test during screening within 72 hours prior to receiving first dose of protocol-indicated treatment, and must agree to follow instructions for using acceptable contraception from the time of signing consent, and at least 120 days (4 months) after her final dose of pembrolizumab.
  9. A male participant must agree to use contraception during the treatment period and for at least at least 120 days (4 months) after the final dose of pembrolizumab. and refrain from donating sperm during this period.
  10. Adequate organ and bone marrow function resulted ≤ 10 days prior to first dose of protocol-indicated treatment:

Exclusion Criteria:

  1. Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
  2. Patients with adult T-cell leukemia/ lymphoma (ATLL)

  3. Has received prior systemic anti-cancer therapy including investigational agents ≤ 4 weeks prior to first dose of study treatment on Cycle 1, Day 1. Could consider shorter interval for kinase inhibitors or other short half-life drugs.

    Note: concurrent use of bexarotene or vorinostat (where the dose has been stable for the 8 weeks prior to initiating therapy on trial) is permitted for CTCL. Concurrent use of topical steroids or therapies for CTCL is allowed.

    Participants must have recovered from all AEs due to previous therapies to ≤ Grade 1 or to baseline value (i.e. condition prior to initiation of the therapy associated with the AE). Participants with ≤Grade 2 neuropathy as AE may be eligible.

    If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.

  4. Pregnant or breast-feeding females. A WOCBP who has a positive urine pregnancy test at screening. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
  5. Has received radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
  6. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  7. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.

  8. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.

    Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.

  9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.

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

    Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.

  11. Active uncontrolled infection requiring systemic therapy (patients must be afebrile for ≥ 48 hours off antibiotics prior to first protocol treatment). If fever is attributed to tumor fever (B symptom) then this criteria would not apply.
  12. Active myocarditis, regardless of etiology; or New York Heart Association (NYHA) functional classification III-IV heart failure.
  13. Known active 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 for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
  14. Disease free of prior malignancies for ≥ 1 year with exception of currently treated basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast. (Other malignancies will require advance discussion and agreement between the investigator and the sponsor-investigator regarding risk of recurrence.)
  15. Known severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  16. Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.
  17. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
  18. Has a history or current evidence of any condition (e.g. renal disease that would preclude treatment or obstructive pulmonary disease and history of bronchospasm), therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  19. Clinically significant history of liver disease, including current alcohol abuse or cirrhosis.
  20. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  21. Has a known history of active TB (Bacillus Tuberculosis).
  22. Prior allogeneic stem cell transplant within last 5 years or active graft vs. host disease (GVHD).
  23. Patients with grade 2 or higher peripheral neuropathy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Brentuximab vedotin (brentuximab) and pembrolizumab

All subjects are scheduled to receive up to 16 cycles of combinatorial treatment with brentuximab + pembrolizumab, followed by up to 19 additional cycles of pembrolizumab monotherapy.

After receiving 35 total doses of pembrolizumab (i.e. scheduled for 16 doses in the combinatorial setting and 8 doses as monotherapy), a subject's pembrolizumab treatment will be complete.
Drug: Brentuximab vedotin
Brentuximab vedotin is an antibody-drug conjugate medication used to treat relapsed or refractory Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL), a type of T cell non-Hodgkin lymphoma. It selectively targets tumor cells expressing the CD30 antigen, a defining marker of Hodgkin lymphoma and ALCL.
Other Names:
  • Adcetris
Drug: Pembrolizumab
Pembrolizumab is a humanized antibody used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast cancer.
Other Names:
  • Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The best overall response with the combination of brentuximab and pembrolizumab.
Time Frame: 3 cycles (63 Days)
As assessed by the Lugano criteria for PTCL(16) and the global response score for CTCL(17)
3 cycles (63 Days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurrence of toxicity
Time Frame: 2 Years
As assessed by using the NCI Common Terminology Criteria for Adverse Events version 5 (CTCAE v5) for grading
2 Years
Progression free survival (PFS)
Time Frame: 2 Years
Defined as the time from enrollment to earliest of progression, death or follow-up
2 Years
Overall survival (OS)
Time Frame: 2 Years
Defined as the time from enrollment to death or last follow-up
2 Years
Time to treatment failure
Time Frame: 2 Years
Defined as interval from initiation of chemotherapy to premature discontinuation for any reason.
2 Years
Duration of response
Time Frame: 2 Years
Defined as the interval from response initiation (when either CR or PR is first determined) to progression or death, whichever occurs first.
2 Years
Time to progression
Time Frame: 2 Years
Defined as the time from treatment initiation to tumor progression.
2 Years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yale University

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Principal Investigator: Tarsheen Sethi, MD, Yale University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 10, 2023

Primary Completion (Estimated)

April 30, 2028

Study Completion (Estimated)

July 30, 2028

Study Registration Dates

First Submitted

March 28, 2022

First Submitted That Met QC Criteria

March 28, 2022

First Posted (Actual)

April 6, 2022

Study Record Updates

Last Update Posted (Actual)

June 11, 2026

Last Update Submitted That Met QC Criteria

June 9, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2000029793
  • No NIH funding (Other Identifier: 11.16.23)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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