A Phase I/II Study of GDA-201, Cryopreserved Nicotinamide-Enhanced Allogeneic Natural Killer Cells, in Patients with Relapsed/Refractory B-Cell Lymphoma

Document Type

Conference Proceeding

Publication Date

2-1-2024

Publication Title

Transplantation and Cellular Therapy

Keywords

cyclophosphamide, fludarabine, interleukin 2, nicotinamide, rituximab, adult, aged, B cell lymphoma, chimeric antigen receptor T-cell immunotherapy, clinical article, cohort analysis, conference abstract, controlled study, cytokine release syndrome, diffuse large B cell lymphoma, drug therapy, ex vivo study, female, follicular lymphoma, graft rejection, graft versus host reaction, human, low drug dose, male, mantle cell lymphoma, marginal zone lymphoma, maximum tolerated dose, multicenter study, natural killer cell, neurotoxicity, neutropenia, oxidative stress, phase 1 clinical trial, phase 2 clinical trial, refractory disease, side effect, special situation for pharmacovigilance, therapy

Abstract

Background: GDA-201 consists of metabolically enhanced ex-vivo expanded allogeneic Natural Killer (NK) cells, manufactured using nicotinamide-based expansion technology. GDA-201 cells exhibit improved homing to lymphoid organs, decreased expression of inhibitory checkpoints, augmented resistance to oxidative stress and competent cytotoxicity. We have previously shown that a fresh formulation of GDA-201 in combination with rituximab was well tolerated and demonstrated clinical efficacy with long term responses in patients (pts) with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL). This is a phase I/II open label, multicenter study evaluating the safety and efficacy of allogeneic cryopreserved GDA-201 in pts with R/R B-NHL (NCT05296525). Methods: The primary objective was to determine the maximal tolerated dose of GDA-201 based on dose limiting toxicities (DLTs). Eligible pts were adults with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma (HGBCL), mantle cell lymphoma (MCL), and marginal zone B-cell lymphoma (MZL) who received ≥2 previous lines of therapy and were ineligible for or had relapsed / refractory disease after CAR-T cell therapy. Response was assessed using Lugano criteria. GDA-201 was administered with rituximab after fludarabine/cyclophosphamide lymphodepletion, followed by low dose IL-2. Pts were enrolled using a 3X3 dose escalation design comprising four dose cohorts (2.5x107, 5 x107, 1x108 and 2x108 cells/kg). Results: Ten pts (5 male, 5 female), median age 64.5 years (range: 40-78), with DLBCL/HGBCL (n=6), MZL (n=2), FL (n=1), and MCL (n=1) were enrolled in 3 dose cohorts up to 1x108 cells/kg. Pts had a median of 6 prior lines of therapy (range: 3-8); 6 pts relapsed after CAR-T cell therapy, and 4 pts relapsed after hematopoietic cell transplant (autologous: 2, allogeneic: 2). There were no infusion reactions, DLTs, or related serious adverse events. The most common grade 3-4 adverse event was neutropenia, reported in all pts. Two pts at 1x108 cells/kg had cytokine release syndrome (1 grade 1, 1 grade 2). No cases of immune effector cell associated neurotoxicity syndrome or graft versus host disease were reported. One pt died of disease progression. Two pts had complete response, 2 pts had partial response and one had stable disease. Responders included 3 pts who had relapsed after CAR-T. Response appears to be dose dependent with 2/3 pts in Cohort 3 responding. Cohort 4, at the target GDA-201 dose level of 2x108 cells/kg, is currently enrolling. Conclusion: GDA-201 with rituximab was well tolerated in doses up to 1x108 cells/kg and demonstrated evidence of clinical efficacy in pts with R/R B-cell NHL including in the post-autologous CAR-T setting.

PubMed ID

Not assigned.

Volume

30

Issue

2

First Page

S196

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