Summary
Updated results from a phase I clinical study of GDA-201, an investigational, natural killer (NK) cell-based cancer immunotherapy for the treatment of patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) were revealed at the 2019 ASH Annual Meeting. Data from 22 patients in the ongoing study showed GDA-201 in combination with monoclonal antibodies was generally well-tolerated and demonstrated early evidence of clinical activity in heavily pre-treated patients, including five complete responses observed among nine patients with NHL. Researchers plan to initiate a phase I/II multi-dose, multi-center study of GDA-201 in patients with NHL in 2020.
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Original Article
NK Cell-Based Therapy for Multiple Myeloma & Non-Hodgkin Lymphoma
Oncology Times
Updated results from a phase I clinical study of GDA-201, an investigational, natural killer (NK) cell-based cancer immunotherapy for the treatment of patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) were revealed at the 2019 ASH Annual Meeting. Data from 22 patients in the ongoing study showed GDA-201 in combination with monoclonal antibodies was generally well-tolerated and demonstrated early evidence of clinical activity in heavily pre-treated patients, including five complete responses observed among nine patients with NHL. Researchers plan to initiate a phase I/II multi-dose, multi-center study of GDA-201 in patients with NHL in 2020.
“NK cells are increasingly recognized as a potential breakthrough approach in immunotherapy, and the data reported today provide early evidence that GDA-201 has the potential to be an important new treatment option,” said Veronica Bachanova, MD, PhD, Associate Professor of Medicine in the Division of Hematology, Oncology and Transplantation at the University of Minnesota and principal investigator of the study through the Masonic Cancer Center. “Given the population of heavily pre-treated patients with advanced disease, it’s particularly encouraging to witness multiple complete responses. I look forward to the continued development of this investigational therapy.”
New research was also presented on the mechanism of action of NAM-based cell expansion platform, which is designed to enhance the number and functionality of allogeneic donor cells. These data provide further scientific rationale for the favorable stem cell engraftment and patient outcomes observed in the phase I/II clinical study of omidubicel, a cell therapy currently in phase III clinical development as a potential lifesaving treatment option for patients in need of an allogeneic bone marrow transplant.
The oral presentation, “Results of a Phase 1 Trial of GDA-201, Nicotinamide-Expanded Allogeneic Natural Killer Cells (NAM-NK) in Patients with Refractory Non-Hodgkin Lymphoma (NHL) and Multiple Myeloma (MM)” (Abstract 777), described data from the phase I clinical study of GDA-201 in heavily pre-treated patients with advanced NHL and MM. Twenty-two patients were enrolled in the study, including nine patients with NHL and 13 patients with MM. Of these 22 patients, all were evaluable for safety and 21 were evaluable for response (NHL = 9; MM = 12).
In the study, cell therapy using GDA-201 with monoclonal antibodies was generally well-tolerated and demonstrated early evidence of clinical activity. Of the nine patients with NHL, five achieved a complete response and one achieved a partial response. Among the patients with MM, one patient achieved a complete response, and five patients achieved stable disease.
GDA-201 was generally well-tolerated, with no graft-versus-host disease (GvHD), tumor lysis syndrome, neurotoxicity, or marrow aplasia observed. No dose-limiting toxicities were observed. Hypertension and hematologic events were the most common grade 3/4 adverse events observed. Most non-hematologic toxicities were attributed to cyclophosphamide/fludarabine, which was used as a pre-conditioning treatment.
The poster presentation, “Nicotinamide (NAM) Modulates Transcriptional Signature of Ex Vivo Cultured UCB CD34+ Cells (Omidubicel) and Preserves Their Stemness and Engraftment Potential” (Abstract 3718), included transcriptome, transcription factor, and pathway analysis to elucidate the pathways leading to the preservation of engraftment after ex vivo expansion of CD34+ hematopoietic stem cells derived from umbilical cord blood (the starting point for omidubicel) compared to CD34+ cells grown in the absence of NAM.
Analyses showed that the presence of NAM reduced the expression of genes involved in the production of reactive oxygen and nitrogen species, suggesting that cell stress was minimized during expansion. In addition, NAM also decreased growth factor pathways responsible for activation and differentiation of hematopoietic stem cells, suggesting NAM expanded cells while keeping them in an undifferentiated state. The presence of NAM also led to a decrease in the expression of genes responsible for matrix-metallo proteinase secretion, simulating the microenvironment of the bone marrow. Additionally, NAM led to an increased expression of telomerase genes, which is believed to enable cells to remain in a more quiescent, stem-like state. These data provide further scientific rationale for the favorable stem cell engraftment and patient outcomes that were observed in the phase I/II clinical study of omidubicel.
GDA-201 (formerly known as NAM-NK) is being developed as an innate natural killer (NK) cell immunotherapy for the treatment of hematologic and solid tumors in combination with standard-of-care antibody therapies. NK cells have the ability to kill tumor cells, representing a novel immunotherapeutic approach to cancer treatment. GDA-201 is designed to address key limitations of NK cells by increasing the cytotoxicity and in vivo retention and proliferation in the bone marrow and lymphoid organs of NK cells expanded in culture. It is in phase I development in patients with refractory non-Hodgkin lymphoma and multiple myeloma.