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Brentuximab Vedotin

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Immunologic Factors

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.

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.

Brentuximab vedotin

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.

Maxime Oriol, BS

Julie Holub

Kylie Boyhen

Tarsheen Sethi, MD

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 \~65%. Pembrolizumab and brentuximab will be administered for 16 cycles in patients with responsive disease. Pembrolizumab will be continued for an additional 19 cycles (total 35 cycles). Response assessments will occur at pre-specified intervals. Dose adjustments for specific toxicities with either drugs are detailed in the protocol. Based on statistical analysis 43 subjects will need to be accrued to evaluate for disease response based on historical control.

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.

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

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

As assessed by the Lugano criteria for PTCL(16) and the global response score for CTCL(17)

As assessed by using the NCI Common Terminology Criteria for Adverse Events version 5 (CTCAE v5) for grading

Defined as the time from enrollment to earliest of progression, death or follow-up

Defined as the time from enrollment to death or last follow-up

Defined as interval from initiation of chemotherapy to premature discontinuation for any reason.

Defined as the interval from response initiation (when either CR or PR is first determined) to progression or death, whichever occurs first.

Defined as the time from treatment initiation to tumor progression.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pembrolizumab and Brentuximab Vedotin in Subjects With Relapsed/Refractory T-cell Lymphoma	NCT05313243	T-Cell Lymphoma	Brentuximab ved... Pembrolizumab	18 Years -	Yale University
Pembrolizumab and Brentuximab Vedotin in Subjects With Relapsed/Refractory T-cell Lymphoma	NCT05313243	T-Cell Lymphoma	Brentuximab ved... Pembrolizumab	18 Years -	Yale University

Spots Global Cancer Trial Database for cd30 positive