The phase 1b KEYNOTE-B79 trial is investigating the allogeneic cell therapy in participants with metastatic colorectal cancer.
Celyad Oncology has voluntarily paused their phase 1b KEYNOTE-B79 clinical trial (NCT04991948) following the report of 2 patient deaths with similar findings.1
The trial, which is evaluating treatment with their investigational CAR T-cell therapy CYAD-101 administered with pembrolizumab (Keytruda; MSD/Merck & Co.) in participants with refractory metastatic colorectal cancer (mCRC) with microsatellite stable (MSS)/mismatch-repair proficient disease, recently dosed its first patient in December 2021.
“Our primary commitment is to maintain patient safety, which is why we decided to place the trial on hold while we investigate these events,” said Filippo Petti, chief executive officer, Celyad Oncology, in a statement. “We are working diligently to better understand these events.”
Two participant fatalities have been recorded thus far, both of whom presented with similar pulmonary findings. Notably, no dose-limiting toxicities were recorded among the 25 participants who were treated in the alloSHRINK phase 1 trial, according to Petti. The company said it is currently investigating the reports and also evaluating any similar events in other treated patients participating in the study.
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 supported evidence of clinical activity in solid tumors. No evidence of graft-versus-host disease was seen and 9 of 10 patients with mCRC showed stable disease at first tumor assessment.
The TCR inhibitory molecule-base allogeneic NKG2D CAR T-cell therapy, which was the first non-gene-edited, “off the shelf” allogeneic cell therapy clinical program to be accepted by the FDA back in 2018, is being investigated in combination with MSD’s anti-PD-1 therapy pembrolizumab after “preclinical data and translational data from our prior phase 1 study of CYAD-101 suggest that there may be an additive benefit with pembrolizumab as an anti-PD-1 checkpoint inhibitor when combined with CYAD-101 in colorectal cancer,” Charles Morris, MD, Celyad chief medical officer, said in a prior statement.2
Further details of the study design were recently presented at the 2022 ASCO GI Symposium, January 20-22, 2022. KEYNOTE-B79 is evaluating the safety and efficacy of 3, bi-weekly, 1x109-cell infusions of CYAD-101 after FOLFOX preconditioning across 5 sites in the US and Europe. Participants will start 200 mg pembrolizumab treatment 3 weeks after last infusion, which will continue every 3 weeks for up to 2 years. The trial is enrolling participants with MSS/mismatch-repair proficient, relapsed/refractory mCRC after at least 1 metastatic line of therapy that included FOLFOX chemotherapy. The trial’s primary end points include safety and efficacy via the occurrence of dose-limiting toxicities (DLTs) and objective response rate (ORR). ORR will be evaluated 6 weeks after first pembrolizumab treatment. Preliminary data from the trial were initially expected to read-out in the second half of 2022.
Celyad is informing regulatory agencies of the findings and noted that they may require additional actions from the company before moving forward.
“We anticipate no impact on our shRNA-based candidates, including CYAD-211 currently under investigation for the treatment of multiple myeloma,” Petti noted.