NEW YORK – Celyad Oncology said on Tuesday that it is partnering with Merck to conduct a study in which its investigational CAR T-cell therapy, CYAD-101, will be evaluated in combination with Merck's anti-PD-1 therapy pembrolizumab (Keytruda) in certain advanced colorectal cancer patients.
In the Phase Ib Keynoted-B79 trial, refractory and metastatic colorectal cancer patients will receive FOLFIRI as preconditioning chemotherapy before receiving CYAD-101 and pembrolizumab, and their tumors must be microsatellite stable or mismatch repair proficient.
Celyad, a Belgium and New York-based biotech company, is developing allogeneic and autologous CAR T-cell therapies for hematologic and solid cancers. Merck, known as MSD outside the US, markets pembrolizumab as a treatment for refractory solid tumors that have high microsatellite instability or mismatch repair deficiency. By combining CYAD-101 with pembrolizumab, the drugmakers hope to bolster the immune system's response to colorectal cancers that are microsatellite stable, since patients in this subgroup tend not to respond well to immunotherapy.
"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," Celyad CEO Filippo Petti said in a statement.
CYAD-101 is an investigational allogeneic CAR T-cell treatment that co-expresses a NKG2D-based chimeric antigen receptor and inhibits T-cell receptor signaling-associated graft-versus-host-disease (GvHD), which occurs when transplanted donor cells attack a patient's tissues. In June, Celyad presented initial data from the Phase I alloSHRINK trial involving 15 relapsed or refractory, metastatic colorectal cancer patients who had progressed after oxaliplatin-based or irinotecan-based chemotherapies.
Two patients achieved a partial response, including one patient who had a KRAS mutation, and nine patients had stable disease. None of the 15 patients had GvHD, though all reported treatment-related adverse events that were grade 1 or 2, with one patient experiencing grade 1 cytokine release syndrome. Based on these results, the company plans to evaluate CYAD-101 in an expansion cohort of refractory, metastatic colorectal cancer patients who have had FOLFIRI preconditioning in the fourth quarter.
"The collaboration with MSD adds an important dimension to our clinical program for CYAD-101 for the treatment of metastatic colorectal cancer and provides us with the opportunity to build upon the encouraging clinical activity we've reported to date from the ongoing alloSHRINK trial," said Petti.