P1, N=12, Recruiting, CytoMed Therapeutics Pte Ltd | Not yet recruiting --> Recruiting | Trial completion date: Dec 2023 --> Dec 2026 | Trial primary completion date: Mar 2023 --> Nov 2025

P1/2, N=17, Recruiting, Leucid Bio

P1, N=36, Recruiting, Zhejiang University

P=N/A, N=9, Recruiting, Zhejiang University

P=N/A, N=9, Terminated, Hangzhou Cheetah Cell Therapeutics Co., Ltd | Phase classification: P1 --> P=N/A | Recruiting --> Terminated; end

P1, N=9, Not yet recruiting, CytoMed Therapeutics Pte Ltd

P1, N=34, Recruiting, Celyad Oncology SA | Not yet recruiting --> Recruiting | Phase classification: P1b --> P1

P1, N=9, Recruiting, Hangzhou Cheetah Cell Therapeutics Co., Ltd

In clinical trials, CYAD-01 showed a good tolerability profile but with a disappointing level of clinical activity when combined with cyclophosphamide / fludarabine preconditioning (DEPLETHINK trial, NCT03466320)...The knockdown of MICA/MICB appears to have a positive contribution to the initial clinical activity of CYAD-02 as compared to that achieved with the first generation CYAD-01 CAR T, together with good safety and tolerability...One approach to further drive the potency of NKG2D-based CAR T cells would likely be armoring the CAR T through using the T cell as a vehicle to secrete cytokines alongside the CAR. Overall, shRNA knockdown technology provides a means to modify CAR T function and here shows that single shRNA can target two independent genes to enhance the phenotype of the CAR Ts.

P1b, N=34, Not yet recruiting, Celyad Oncology SA

Results As compared to CYAD-01, CYAD-02 cell expansion in vitro was 3-fold increased...The study evaluates three dose-levels of CYAD-02 (1x108, 3x108 and 1x109 cells/infusion), administered as a single infusion after non-myeloablative preconditioning chemotherapy (cyclophosphamide 300 mg/m²/day and fludarabine 30 mg/m²/day, daily for 3 days, CyFlu) according to a classical Fibonacci 3+3 design...This next generation NKG2D CAR T-cell product is currently investigated in the CYCLE-1 Phase I study in r/r AML/MDS patient population, a difficult to target disease due in part to the absence of truly AML-specific surface antigens, its rapid clinical progression and the absence of disease control by the CyFlu preconditioning. Both the anti-MICA and MICB shRNA hairpin and the OptimAb manufacturing process for CYAD-02 aim to improve CAR T-cell persistence and clinical responses.

Fifteen refractory metastatic CRC patients who had previously failed at least one line of oxaliplatin—containing therapy were treated with three doses of CYAD-101 cells given on Day 3 of three successive FOLFOX chemotherapy cycles. These early clinical results demonstrate the safety and tolerability of a non-gene edited predominantly CD4+ CAR-T therapeutic approach. The initial observations of clinical activity in metastatic CRC patients warrants the continued development of this therapy. Research Funding: Celyad SA