FDA Lifts Clinical Hold on KEYNOTE-B79 Trial of a Novel CAR T-Cell Agent in mCRC

The CYAD-101-002 trial may resume after the FDA lifted the partial clinical hold to evaluate risk to study patients with metastatic colorectal cancer.

The FDA has lifted the clinical hold on the phase 1b CYAD-101-002 trial (KEYNOTE-B79; NCT04991948), which is evaluating the safety and clinical activity of the investigational chimeric antigen receptor (CAR T)-cell therapy CYAD-101 when given in addition to FOLFOX (leucovorin, 5-fluorouracil, and oxaliplatin) and followed by pembrolizumab (Keytruda) in patients with unresectable metastatic colorectal cancer (mCRC), according to Celyad Oncology SA.1

The voluntary pause was initially placed on February 28, 2022, and put on clinical hold in March 2022 by the FDA due to insufficient information to evaluate risk to study participants and to further examine reports of 2 fatalities that presented with 2 pulmonary findings which occurred on the study.2

Now that changes have been made to the eligibility criteria of the trial, the lift has occurred, allowing for the dosing and enrollment of patients in the KEYNOTE-B79 trial to continue.

“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 TCR inhibitory molecule [TIM] 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,” said Charles Morris, MD, chief medical officer of Celyad Oncology, in the press release.

CYAD-101 is an investigational, non-gene edited allogeneic CAR T candidate designed to co-express the chimeric antigen receptor based on NKG2D. NKG2D is a receptor which is expressed on natural killer (NK) cells and binds to 8 stress-induced ligands (NKG2DL) expressed by a broad range of tumor cells and the novel inhibitory peptide TIM. TIM is engineered to reduce signaling of the TCR complex by interfering with a component of the TCR complex.3

Within the open-label, phase 1b trial, investigators aim to evaluates the TIM-based allogeneic NKG2D CAR T-cell investigational therapy, CYAD-101, with pembrolizumab, an anti-PD-1 therapy, in patients with refractory mCRC with microsatellite stable (MSS) and/or mismatch-repair proficient disease.

Enrollment in the trial is open to patients aged 18 years and older with historically proven metastatic adenocarcinoma of the colon or rectum, an ECOG performance status of 0 or 1, and acceptable organ, hepatic, renal, pulmonary, cardiac functions, and who had a tumor biopsy at screening.4

Patients enrolled in the trial will be given CYAD-101 and a FOLFOX infusion which will be administered concurrently followed by pembrolizumab. The primary end points of the trial include the occurrence of dose limiting toxicities and objective response rate at the tumor assessment on day 94.

The study is estimated to enroll 34 patients and has a study completion date set for May 25, 2038.

References:
  1. Celyad oncology announces FDA lifts clinical hold of CYAD-101-002 phase 1b trial. News release. Celyad Oncology SA. August 1, 2022. Accessed August 1, 2022. https://yhoo.it/3QbEqGo
  2. Celyad Oncology announces voluntary pause of CYAD-101-002 phase 1b trial. News release. Celyad Oncology SA; February 28, 2022. Accessed August 1, 2022. https://bit.ly/3JsC4kb
  3. Celyad Oncology SA. Pipeline. Accessed August 1, 2022. https://bit.ly/3BvkE4s
  4. Phase 1b study to evaluate the addition of a pembrolizumab treatment after treatment with CYAD-101 with a FOLFOX preconditioning in metastatic colorectal cancer patients. ClinicalTrials.gov. Updated March 9, 2022. Accessed August 1, 2022. https://clinicaltrials.gov/ct2/show/NCT04991948