RAPA-201 T Cell Therapy for Relapsed, Refractory Multiple Myeloma

This clinical trial evaluates autologous rapamycin-resistant Th1/Tc1 (RAPA-201) cells for therapy of relapsed, refractory multiple myeloma (RRMM). The study population of RRMM patients is defined by: relapse after ≥ 3 prior regimens; exposure to ≥ 2 proteasome inhibitors (PI) (e.g. bortezomib), ≥ 2 immunomodulatory agents (IMiD) (e.g. lenalidomide), and ≥ 1 anti-CD38 monoclonal antibody (e.g., daratumumab); and refractory status to ≥ 1 PI agent and ≥ 1 IMiD agent. The primary study objective is to determine the overall response rate, as evaluated by IMWG criteria, of RAPA-201 cells and a pentostatin-cyclophosphamide (PC) host conditioning regimen in patients with RRMM. A sample size of 22 patients was selected to determine whether RAPA-201 therapy represents an active regimen in RRMM, as defined by a response rate (≥ partial remission) consistent with a 35% rate.

Multiple myeloma (MM) is an incurable cancer characterized by clonal proliferation of plasma cells. MM is the second most common form of hematologic malignancy in the United States, with approximately 11,000 individuals dying from the disease in 2014. Due in part to the aging population, MM prevalence will dramatically increase in the next few decades. MM management has many FDA-approved options for the up-front setting, maintenance therapy, and therapy at second or third relapse. For patients with relapsed MM, therapy typically consists of triplet regimens approved by the U.S. Food and Drug Administration (FDA), including the KRd, DRd, and DPd regimens. Although triplet regimens are improved relative to prior therapies, they typically provide a progression-free survival of less than two years and cause substantial toxicities. Few standard, effective options exist for patients with MM who have more advanced disease and higher levels of drug refractoriness. In contrast to drug and monoclonal antibody therapy, which are essentially non-curative, T cell therapy can cure MM, as evidenced by long- term survival in recipients of allogeneic hematopoietic cell transplantation. The promise of T cell therapy against MM is further exemplified by high response rates using gene-modified autologous CAR-T cell therapy directed against the BCMA target. However, CAR-T therapy is limited by variable tumor cell target expression, which compromises response durability leading to relapse. Furthermore, CAR-T cell products are expensive to manufacture, with the financial burden further complicated by frequent inpatient hospital monitoring and treatment of potentially lethal toxicities that include cytokine storm and neurologic damage. Thus, a great need exists to develop novel T cell therapies for RRMM that are safe, cost effective, and curative. We will evaluate one such promising candidate, namely, autologous rapamycin-resistant Th1/Tc1 cells (RAPA-201).