Celyad Announces Positive Data and Updates for CAR T Candidates

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The phase 1b KEYNOTE-B79 trial of CYAD-101 for mCRC is expected to initiate in Q4 2021.

Celyad Oncology announced positive data from its phase 1 IMMUNICY-1 trial evaluating CYAD-211 in relapsed/refractory multiple myeloma (R/R MM) as well as updates on its chimeric antigen receptor T cells (CAR T) pipeline.

CYAD-211 showed dose-dependent engraftment up to dose level 3 of 300 x 106 cells per infusion with no Graft-versus-Host disease (GvHD) reported to date. Meanwhile, investigational new drug (IND) submission for CYAD-203 is expected in mid-2022 and CYAD-101 has shown efficacy in advanced metastatic colorectal cancer (mCRC).

“We believe the advances we’re making may address many of the current modality limitations and have the potential to provide real-world benefits for patients, including more accessible CAR T cell treatment options, if approved. This continued technological innovation, which is currently being validated in ongoing clinical studies, establishes Celyad Oncology as a leader in this adoptive cell therapy space," said Filippo Petti, chief executive officer, Celyad Oncology, in a statement.

CYAD-211 for Relapsed/Refractory Multiple Myeloma

CYAD-211 is an shRNA-based allogenic CAR T candidate that expresses a B-cell maturation antigen targeting chimeric antigen receptor while using shRNA to deregulate expression of the CD3ζ component of the T-cell receptor. It is currently being evaluated in the phase 1 IMMUNICY trial for the treatment of R/R MM following 3 consecutive days of cyclophosphamide (300 mg/m2) and fludarabine (30 mg/m2) conditioning.

Preliminary data from the IMMUNICY-1 trial was presented at the European Hematology Association 2021 congress in June. These data demonstrated no dose limiting toxicity, GvHD, or CAR T-cell related encephalopathy syndrome with treatment of the 30 x 106 and 100 x 106 cells per infusion dosages of CYAD-211. Two of the 5 evaluable patients treated with those dosages achieved a partial response and CYAD-211 cells were detected by polymerase chain reaction-based methods in all 6 patients with evidence of a dose-dependent increase in cell engraftment.

More recent data from the first patient dosed with 300 x 106 cells per infusion showed that dose dependent engraftment has continued with no GvHD to date. Enrollment for IMMUNICY-1 is ongoing and Celyad plans to explore higher preconditioning regimen doses for future cohorts. Additional data from IMMUNICY-1 is expected in early Q4 2021.

CYAD-203 for Solid Tumors

CYAD-203 is shRNA-based and the company’s first “armored” CAR T candidate engineered to express the cytokine interleukin-18 (IL-18) with the NKG2D CAR receptor. The candidate is designed to take advantage of IL’18’s proinflammatory cytokine activity to directly potentiate the anti-cancer activity of CAR T cells while also altering the balance of pro- and anti-inflammatory cells within tumor tissue. IND-enabling studies are being conducted with CYAD-203 and the company hopes to be able to submit the IND application in mid-2022.

WATCH NOW: Mitigating Adverse Events in CAR T-Cell Therapy: Mounzer Agha, MD

CYAD-101 for Advanced Metastatic Colorectal Cancer

CYAD-101 is an allogenic TIM-based NKG2D CAR T for the treatment of mCRC. Data from the dose-escalation segment of the alloSHRINK phase 1 trial evaluating the treatment following FOLFOX (combination of 5-fluorouracil, leucovorin and oxaliplatin) preconditioning chemotherapy supports evidence of clinical activity in solid tumors. Further data from the dose expansion cohort of 1 x 109 cells per infusion of CYAD-101 following FOLFIRI (combination of 5-fluorouracil, leucovorin and irinotecan) preconditioning chemotherapy demonstrated that the treatment was generally well-tolerated. No dose limiting toxicities or evidence of GvHD was seen and 9 of 10 patients with mCRC showed stable disease at first tumor assessment.

Data also showed support of using FOLFOX precondition rather than FOLFIRI preconditioning, with shorter persistence of CYAD-101 cells seen after FOLFIRI preconditioning. The phase 1b KEYNOTE-B79 trial, which is planned to initiate in Q4 2021 will use FOLFOX as preconditioning chemotherapy. The trial will evaluate CYAD-101 with pembrolizumab (Keytruda; Merck) in patients with mCRC and microsatellite stable/mismatch-repair proficient disease.

“We are ushering in a new era of allogeneic CAR T candidates using novel technological advances, including our proprietary shRNA platform for allogeneic CAR T production and now the addition of our 'armored' CAR capabilities with co-expression of the cytokine IL-18,” Petti added.

Celyad also recently entered into a licensing agreement with Moffitt Cancer Center to use their antibody directed to Tumor-associated glycoprotein. The company plans to use the antibody to form a T cell engager to be used with their proprietary shRNA platform for solid tumor targets. TAG-72 has previously been shown to be expressed in a wide variety of epithelial malignant tissues such as breast, colon, and pancreatic cells.

REFERENCE
Celyad Oncology presents updates on allogeneic CAR T clinical candidates and shRNA-based preclinical concepts at research & development day. News release. Celyad Oncology. July 20, 2021. https://www.businesswire.com/news/home/20210720005854/en/Celyad-Oncology-Presents-Updates-on-Allogeneic-CAR-T-Clinical-Candidates-and-shRNA-based-Preclinical-Concepts-at-Research-Development-Day
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