First Non-Gene Edited CAR-T to Partner with Merck’s Blockbuster Against Colorectal Cancer

By Judy Ya-Hsuan Lin

Microsatellite stable (MSS) metastatic colorectal cancer (mCRC) was treated with traditional chemotherapy until the advent of immunotherapy. CYAD-101 is the first and ongoing investigational immunotherapy for MSS mCRC, developed by clinical-stage biotech, Celyad Oncology, based in Belgium. CYAD-101 is a non-gene edited, allogeneic CAR T candidate engineered to co-express a chimeric antigen receptor-based on NKG2D, a receptor expressed on natural killer (NK) cells that binds to eight stress-induced ligands and the novel inhibitory peptide TIM (TCR Inhibitory Molecule). The development of CAR T therapies for cancer is what Celyad has been focusing on since 2007. Celyad has a pipeline for allogeneic and autologous CAR T cell therapy candidates to treat both hematological malignancies and solid tumors.

According to the results of alloSHRINK Phase 1 trial presented at the Society for Immunotherapy of Cancer (SITC) 34th Annual Meeting last year, CYAD-101 demonstrated an absence of graft-versus-host disease thanks to the expression of TIM, which reduced signaling of the TCR complex responsible for graft-versus-host disease, when administered concurrently with FOLFOX chemotherapy. Additionally, two patients achieved a partial response, and nine patients achieved stable disease, indicating a disease control rate of 73%. The overall safety and clinical activity data were human leukocyte antigen (HLA)-independent, indicating that CYAD-101 can be applied in a broad patient population regardless of the HLA haplotype.

This year, Celyad decides to further examine CYAD-101’s efficacy in refractory mCRC patients with MSS or mismatch-repair proficient (pMMR) disease, by combining with the anti-PD-1 drug Keytruda developed by Merck & Co., Inc. They will collaborate in the Phase Ib KEYNOTE-B79 clinical study. The combination of CYAD-101 and Keytruda will be followed by FOLFIRO, a chemotherapy regimen for the treatment of colorectal cancer. This brings Celyad to No. 3 in Zacks Stock Rank.

Filippo Petti, CEO of Celyad, said, “we are extremely pleased to enter into this clinical collaboration with MSD, as we believe the mechanism of actions of CYAD-101 and KEYTRUDA are highly complementary and could help to drive meaningful clinical benefit in patients with advanced metastatic colorectal cancer, in particular with microsatellite stable disease where a high unmet medical need exists.”

“The collaboration with MSD adds an important dimension to our clinical program for CYAD-101 for the treatment of mCRC and provides us with (the) opportunity to build upon the encouraging clinical activity we’ve reported to date from the ongoing alloSHRINK trial,” he added.

Editor: Rajaneesh K. Gopinath, Ph.D.

Related Article: ASCO 2020: Celyad’s Off the Shelf CAR-T Cell Therapy Shows Promise against Colorectal Cancer

References

1. https://celyad.com/2020/09/29/celyad-oncology-announces-clinical-trial-collaboration-to-evaluate-cyad-101-with-keytruda-pembrolizumab-in-patients-with-microsatellite-stable-mcrc/

Author

Judy Ya-Hsuan Lin

Success is the ability to go from one failure to another with no loss of enthusiasm.