FDA Lifts Clinical Hold on Trial Assessing CYAD-101 Plus Pembrolizumab and FOLFOX in Advanced CRC


Development on CYAD-101 as a treatment for patients with refractory/metastatic colorectal cancer continues after the FDA has lifted a clinical hold on the phase 1b CYAD-101-002 trial.

The FDA has lifted a clinical hold that was placed on the phase 1b CYAD-101-002 trial (NCT04991948), assessing the use of pembrolizumab (Keytruda) following treatment with CYAD-101 and leucovorin, fluorouracil, and oxaliplatin (FOLFOX) preconditioning for patients with refractory/metastatic colorectal cancer (CRC), according to a press release from Celyad Oncology.1

The hold on the CYAD-101-002 study, which was placed by the FDA in March 2022 due to concerns around patient risk,2 was lifted following adjustments to the trial’s eligibility criteria. In particular, the trial was paused voluntarily to assess 2 fatalities that occurred on the study.

“We are pleased that the FDA lifted the clinical hold on this trial. We remain confident in the potential development of not only the candidate itself, but the continued development with our proprietary TIM [TCR inhibitory model] technology. CYAD-101 is currently our only clinical candidate co-expressing NKG2D and TIM, and we hope to continue to showcase our expertise with our non-gene edited technologies and explore additional opportunities to utilize NKG2D in allogeneic CAR T, Charles Morris, MD, chief medical officer at Celyad Oncology, stated in the press release.

The study has an estimated enrollment of 34 patients who will receive CYAD-101, TIM–based allogeneic NKG2D chimeric antigen receptor T-cell therapy, and FOLFOX followed by pembrolizumab. The primary end points of the trial were the incidence of dose-limiting toxicities and objective response rate at day 94.

CYAD-101 was also assessed as part of the phase 1 alloSHRINK study (NCT03692429) in patients with unresectable metastatic CRC.3 Of the 15 patients included in the study, no grade 3 or higher adverse effects or graft-versus-host disease were identified following infusion. Moreover, the treatment induced 2 confirmed partial responses, with 1 patient being KRAS positive. Stable disease was reported in 9 patients, with 7 events lasting a minimum of 3 months. Median progression-free survival was 3.9 months. Although engraftment was observed following all infusions, relative systemic cytokine level was mostly altered via cell dose, with investigators believing that the scale of modulation could be associated with response.

“The preliminary translational analysis present intriguing observations that the modulation of systemic cytokine levels may be associated with dose which is uncommon in CAR T-cell therapies reported to date while limited T-cell clonal diversification in the best responding patient underscores the likely central role of the adoptively transferred T-cell in driving therapeutic response in this particular patient,” the study’s investigators concluded.


  1. Celyad Oncology announces FDA lifts clinical hold of CYAD-101-002 phase 1b Trial. News release. August 1, 2022. Accessed August 2, 2022. https://yhoo.it/3OZffWh
  2. Celyad Oncology announces clinical hold of CYAD-101-002 phase 1b trial. News release. Celyad Oncology. March 2, 2022. Accessed August 2, 2022. https://yhoo.it/36Q8DJv
  3. Prenen H, Dekervel J, Hendlisz A, et al. Updated data from alloSHRINK phase I first-in-human study evaluating CYAD-101, an innovative non-gene edited allogeneic CAR-T in mCRC. J Clin Oncol. 2021;39(suppl 3):74-74. doi:10.1200/JCO.2021.39.3_suppl.74
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