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

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.