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

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.