A prospective phase I/IIa trial to evaluate the safety and efficacy of GTA002, an off-the-shelf, ex vivo-cultured allogeneic NK cell preparation in patients with acute myeloid leukemia in complete morphological remission who have measurable residual disease.

Abstract

TPS7053 Background: Acute myeloid leukemia (AML) is a malignant disease with poor long-term prognosis in patients who cannot achieve morphological and molecular remission. Although insights into AML biology and treatment modalities have improved over recent years and even though many patients achieve morphological complete remission (CR), most are still relapsing. These relapses are due to residual leukemia stem cells that can be identified as minimal/measurable residual disease (MRD), with MRD serving as a predictive factor for relapse and mortality. Elimination of MRD in patients having reached CR is seen as essential for optimal and persistent clinical responses. A promising approach is the development of adoptive immunotherapies aimed at directly eradicating tumor cells using T-cells or natural killer (NK) cells. NK cells are part of the body’s innate immune system and play a key role in controlling viral infections and conducting tumor immunosurveillance. Furthermore, NK cells can be applied clinically in an allogeneic setting, enabling the supply of high numbers of immune effector cells, which were not exposed to cytotoxic chemotherapeutics. A proprietary ex vivo expansion and differentiation method in a fully closed, automated manufacturing platform was developed to generate GTA002, an “off-the-shelf” (allogeneic), cryopreserved NK cell preparation, generated from CD34+ hematopoietic stem and progenitor cells derived from umbilical cord blood. The safety and tolerability of the product was already demonstrated in a Phase I trial in elderly patients with AML (PMLA25) (Dolstra et\xa0al. 2017). Methods: We are currently conducting a prospective 2-stage, open-label, single arm, multicenter Phase I/IIa trial to evaluate the safety and efficacy of GTA002 in 33 adults with AML who are in CR with MRD and who are not proceeding to allogeneic HSCT (ClinicalTrials.gov Identifier: NCT04632316). Patients enrolled in the clinical trial receive a lymphodepleting conditioning regimen consisting of cyclophosphamide and fludarabine (Cy/Flu) followed by up to 3 NK cell infusions 4 days apart and will be followed up for 12 months. The dose escalation stage of the trial will assess the safety and tolerability of repeat NK cell infusions in a 3+3 design with 3 cohorts and a cumulative dose range of 325 to 3,000 x106 viable NK cells. The expansion stage will evaluate the safety, tolerability and efficacy of NK cell infusions in 24 additional subjects. The primary efficacy endpoint is the cumulative incidence of the MRD response and secondary efficacy endpoints include the duration of the MRD response, event-free survival, overall survival and cumulative incidence of relapse. Enrollment in the first cohort (one single NK cell infusion) started in December 2020. Clinical trial information: EudraCT number 2019-003686-17.