An analysis of a first-in-human study of NEXI-001 donor-derived antigen-specific CD8+ T-cell treatment of relapsed AML after allogeneic hematopoietic cell transplantation (HCT).

Authors

null

Monzr M. Al Malki

City of Hope, Duarte, CA

Monzr M. Al Malki , Sumithira Vasu , Dipenkumar Modi , Suzanne D Afonso-Smith , Sojung Kim , Emily Lu , Guido Marcucci , Mathias Oelke , Robert D. Knight , Juan Carlos Varela

Organizations

City of Hope, Duarte, CA, The Ohio State University, Columbus, OH, Karmanos Cancer Institute/Wayne State University, Detroit, MI, NexImmune, Inc, Denville, NJ, NexImmune, Inc, Gaithersburg, MD, City of Hope National Medical Center, Duarte, CA, NexImmune, Gaithersburg, MD, Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, MA, MA

Research Funding

Pharmaceutical/Biotech Company
NexImmune, Inc

Background: NEXI-001 is a non-genetically engineered donor-derived cellular therapy product consisting of > 90% CD3+/CD4- T cells that includes significant numbers of CD8+ T cells that are of early memory subtypes and target 5 specific HLA 02.01-restricted peptides from the WT1, PRAME, and Cyclin A1 antigens that are commonly expressed on AML blasts and leukemic stem cells. Methods: AML patients who relapse after allogeneic HCT have a high unmet medical need. These patients have a poor prognosis (2-year survival rate < 10%) and few treatment options. Currently 11 patients have completed the 4-week dose-limiting toxicity (DLT) period in the 3+3 design of the dose-escalation stage of this NEXI-001 phase I trial. The following doses of NEXI-001 T cells were administered during the DLT period: Cohort 1, 4 patients received an infusion of 50M (million) to 100M T cells; Cohort 2, 4 patients received an infusion of 200M T cells; and Cohort 3, 3 patients received infusions of 200M T cells on Days 1, 8, and 15. Results: The NEXI-001 antigen-specific T cells were found to persist and expand in peripheral blood, traffic to bone marrow, and maintain a less differentiated immunophenotype in blood and bone marrow for ≥3 months. No DLTs have occurred. NEXI-001-related adverse events have included grade 2 cytokine release syndrome (2), grade 1 diarrhea (2), grade 2 orthostatic hypotension (1), and a grade 3 GvHD of the gut in week 3 of the first NEXI-001 cycle that resolved within 72 hours with corticosteroid treatment. Clinical activity consisting of the following have occurred in patients within each cohort; neutrophil and platelet count recovery resulting in decreased transfusions and decreases in blasts in peripheral blood and bone marrow. A patient who achieved an MRD- remission following bridging therapy and then was administered a single infusion of 200M NEXI-001 T cells has continued to remain in CR at 6 months of follow-up. A patient in Cohort 3 who relapsed after alloHCT with extramedullary disease manifested by a pleural effusion has achieved a 45% decrease of the symptomatic moderate effusion at baseline to an asymptomatic small effusion after the administration of three 200M NEXI-001 T cells on Days 1, 8, and 15 of the first 4-week cycle. The patient remains asymptomatic at 3 months of follow-up with no detectable AML blasts in peripheral blood or bone marrow and a stable small effusion. A PET scan of the chest showed no areas of increased uptake. Conclusions: Early results indicate that the antigen-specific NEXI-001 T cells have the potential to enhance GvL effects and is tolerated with easily manageable side effects. Greater clinical activity has been observed with increased doses of the NEXI-001 T cells. The trial remains ongoing, and the data support an Expansion Cohort of the study that will allow for a more complete assessment of clinical activity. Clinical trial information: NCT04284228.

Disclaimer

This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org

Abstract Details

Meeting

2023 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Track

Hematologic Malignancies

Sub Track

Acute Leukemia

Clinical Trial Registration Number

NCT04284228

Citation

J Clin Oncol 41, 2023 (suppl 16; abstr 7043)

DOI

10.1200/JCO.2023.41.16_suppl.7043

Abstract #

7043

Poster Bd #

173

Abstract Disclosures