NCT05313243

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

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 32 (estimated)
• Sponsor: Yale University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

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.

Conditions

• T-Cell Lymphoma

Interventions

Type	Name	Description
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.
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.

Timeline

• Start date: 2023-07-10
• Primary completion: 2028-04-30
• Completion: 2028-07-30
• First posted: 2022-04-06
• Last updated: 2025-03-20

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study