Celyad Announces Complete Data from Discontinued CAR in Patients With AML, MDS, MM

Celyad Oncology’s first-generation autologous chimeric antigen receptor (CAR) T-cell therapy CYAD-01 did not significantly improve clinical outcomes in patients with relapsed/refractory acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or multiple myeloma (MM) in the phase 1 THINK study (NCT03018405).¹ The data, from the now-completed study, reinforce the clinical futility of CYAD-01 that led the company to discontinue development of it in December 2020.²

THINK registered 25 participants between February 2017 and October 2018. After 7 patients had manufacturing failures and 2 had screening failures, 16 were treated with CYAD-01: 3 with MM and 3 with AML were treated at dose level 1 (DL1), 3 with AML were treated at DL2, and 6 with AMK and 1 with MDS were treated at DL3. Participants had a median follow-up of 118 days (interquartile range, 46-180).

Investigators observed that 7 participants (44%) had grade 3 or 4 treatment-related AEs and 5 participants (31%) had grade 3 or 4 cytokine release syndrome (CRS). One participant in DL3 had a dose-limiting toxicity of CRS, but altogether the maximum tolerated dose was not reached, and no treatment-related deaths occurred. Three of 12 (25%) evaluable patients with AML or MDS had an objective response. Two patients with AML were able to receive an allogeneic hematopoietic stem-cell transplantation after CYAD-01 treatment and continue to have remission at 5 and 61 months follow-up.

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“These phase 1 data support the proof-of-concept of targeting NKG2D ligands by CAR T-cell therapy. Further clinical studies with NKG2D-based CAR T-cells are warranted, potentially via combinatorial antigen targeted approaches, to improve anti-tumor activity,” first author David A. Sallman, MD, hematologist/oncologist, Moffitt Cancer Center, and colleagues concluded.¹

CYAD-01 was Celyad’s first autologous CAR T-cell therapy candidate. Celyad also shelved its second autologous candidate, CYAD-02, for similar indications, in 2022. Although the company later shifted its focus to developing allogeneic CAR T-cell therapies, insufficient clinical activity once again led to the discontinuation of the allogeneic CYAD-101 in October 2022, followed by serious AEs seen in Celyad’s last remaining clinical-stage program, CYAD-211 for treating MM, which the company then decided to discontinue instead of changing eligibility criteria in December 2022.³ With no remaining clinical programs, Celyad made several organizational changes to cut costs and plans to focus on discovery research around NKG2D, B7-H6 and shRNA platforms.

“In summary, while our clinical results have not lived up to expectations, we are hopeful for the many patients who have been successfully treated in these programs and the solid foundation it has created to move these therapies further. We believe that our clinical accomplishments, strengthened with the current and future research efforts, can lead to commercially successful products,” the company wrote in a letter to stakeholders.³

REFERENCES

1. Sallman DA, Kerre T, Havelange V, et al. CYAD-01, an autologous NKG2D-based CAR T-cell therapy, in relapsed or refractory acute myeloid leukaemia and myelodysplastic syndromes or multiple myeloma (THINK): haematological cohorts of the dose escalation segment of a phase 1 trial. Lancet Haematol. Published online February 07, 2023. doi: 10.1016/S2352-3026(22)00378-7
2. Celyad Oncology Provides Updates on Allogeneic and Autologous CAR T Programs at 62nd ASH Annual Meeting and Exposition. News release. Celyad Oncology. December 7, 2020. https://celyad.com/2020/12/07/celyad-oncology-provides-updates-on-allogeneic-and-autologous-car-t-programs-at-62nd-ash-annual-meeting-and-exposition/
3. Letter to Shareholders. News release. Celyad Oncology. March 3, 2023. https://celyad.com/2023/03/01/letter-to-shareholders/