UPDATED RESULTS FROM PHASE I TRIALS ASSESSING A NKG2D CAR T-CELL APPROACH IN RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA AND MYELODYSPLASTIC SYNDROME PATIENTS
Author(s): ,
David A. Sallman
Affiliations:
Moffitt Cancer Center,Tampa,United States
,
Marco Davila
Affiliations:
Moffitt Cancer Center,Tampa,United States
,
Jason B. Brayer
Affiliations:
Moffitt Cancer Center,Tampa,United States
,
Tessa Kerre
Affiliations:
Gent University Hospital,Ghent,Belgium
,
Xavier Poiré
Affiliations:
Cliniques Universitaires Saint-Luc, Université Catholique de Louvain,Brussels,Belgium
,
Violaine Havelange
Affiliations:
Cliniques Universitaires Saint-Luc, Université Catholique de Louvain,Brussels,Belgium
,
Philippe Lewalle
Affiliations:
Institut Jules Bordet, Université Libre de Bruxelles,Brussels,Belgium
,
Samer Al-Homsi
Affiliations:
New York University School of Medicine,New York,United States
,
Enkhtsetseg Purev
Affiliations:
UCHealth University of Colorado Hospital,Denver,United States
,
Eunice S. Wang
Affiliations:
Roswell Park Comprehensive Cancer Center,Buffalo,United States
,
Panagiota A. Sotiropoulou
Affiliations:
Celyad,Mont-Saint-Guibert,Belgium
,
Nathalie Braun
Affiliations:
Celyad,Mont-Saint-Guibert,Belgium
,
Caroline Lonez
Affiliations:
Celyad,Mont-Saint-Guibert,Belgium
Anne Flament
Affiliations:
Celyad,Mont-Saint-Guibert,Belgium
EHA Library. Sallman D. Jun 15, 2019; 266829; PS1212
David Sallman
David Sallman
Contributions
Abstract

Abstract: PS1212

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
CYAD-01 cells are chimeric antigen receptor (CAR) T cells based on the NKG2D receptor fused to the intracellular domain of CD3ζ, and bind ligands (MICA/B, ULBP1-6) expressed by a large variety of malignancies, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

Aims
A comprehensive clinical program was developed with the objective to define the optimal CYAD-01 treatment in relapsed/refractory (r/r) AML/MDS patients (pts).

Methods

The Phase I THINK trial (NCT03018405) assesses the safety and clinical activity of multiple CYAD‑01 infusions without preconditioning chemotherapy in various malignancies, including r/r AML, MDS and multiple myeloma (MM). 3 dose levels (DL) were evaluated in the dose escalation segment (3x108, 1x109 and 3x109 T-cells/inf.). 1st cycle of treatment consists of 3 CYAD-01 infusions every 2 weeks and a 2nd cycle of 3 CYAD-01 infusions with a 2 week-interval in case of no progressive disease (PD) after the 1st cycle. Additional cohorts aim to provide a dense treatment schedule at the same DL (3x 1 CYAD-01 every week + 3x 1 CYAD-01 every 2 weeks). The Phase I/II DEPLETHINK study (NCT03466320) evaluates the safety and preliminary efficacy of 1 CYAD-01 infusion administered after preconditioning with cyclophosphamide and fludarabine to pts with r/r AML/MDS. A 2nd cycle of 3 CYAD-01 without preconditioning is administered in case of no PD after 1st treatment. 3 DL (1x108, 3x108 and 1x109 cells/inf.) and 2 intervals between preconditioning and CYAD-01 infusion are evaluated in the dose escalation segment. Data as of February 20, 2019 are presented.

Results

THINK study: 16 pts were enrolled in the dose-escalation segment of the hematological cohort, now completed. 4 pts were enrolled in cohorts with the dense schedule. In total, 7 pts experienced grade (G) 3/4 treatment-related adverse events (AEs). Cytokine release syndrome (CRS) occurred in 10 pts with only 2 G3 CRS (at DL2) and 1 G4 CRS (at DL3), which resolved with early tocilizumab treatment. No treatment-related neurotoxicity AEs have been observed.

Out of 12 pts who received at least 3 CYAD-01 infusions in the dose-escalation segment, 2 pts with MM did not have evidence of clinical response. For pts with r/r AML/MDS, 4/10 pts had overall response (OR) at D29 with 1 complete remission (CR) with partial hematologic recovery (CRh) for 16 months in a r/r AML pt at DL-1, 2 CR with incomplete hematologic recovery (CRi) for 1 month in AML pts at DL-1 and DL-3, and 1 marrow CR (mCR) for 1 month in an MDS pt at DL-3. 2 AML pts at DL-2 had stable disease (SD) with bone marrow (BM) blast percentage decrease upon 1st treatment cycle and further reduction upon 2nd treatment cycle. Two other AML pts in DL-3 achieved SD for at least 2 months. 2 AML pts did not show evidence of clinical response. 

DEPLETHINK study: 6 pts were enrolled in the first 2 cohorts which evaluated 1x108 cells/inf. In total, there were 3 G3/4 treatment-related AE observed in the same pt. Five CRS occurred in 4 pts: 3 G1/2 after the 1st infusion and 2 CRS during 2nd cycle (1 G4 CRS and 1 G1), which resolved with tocilizumab treatment. At the 1st cohort, 2 pts reached a stable disease (SD) at D36, allowing the initiation of the 2nd cycle of 3 CYAD-01 infusions.

Conclusion

Altogether, results obtained to date in both phase 1 trials demonstrate the safety of CYAD-01 with or without preconditioning chemotherapy in patients with r/r hematological malignancies. A promising OR rate of 40% at D29 was seen in pts with r/r AML/MDS in the THINK study. The DEPLETHINK study is still accruing.

 

Session topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical

Keyword(s): Acute myeloid leukemia, Adoptive immunotherapy

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies