Clinical Hold Placed on Trial of CAR T-Cell Therapy for Metastatic Colorectal Cancer

The FDA has placed a clinical hold on a trial evaluating the safety and clinical activity of an investigational chimeric antigen receptor (CAR) T-cell therapy for the treatment of colorectal cancer.

The phase 1b CYAD-101-002 trial (KEYNOTE-B79; NCT04991948is investigating the CAR T-cell therapy CYAD-101 administered simultaneously in combination with FOLFOX (leucovorin, 5-fluorouracil, and oxaliplatin) and then followed by pembrolizumab (Keytruda) in patients with unresectable metastatic colorectal cancer (mCRC).¹ The FDA placed the hold because of insufficient information to analyze the risk to patients in the, according to a press release issued by Celyad Oncology.

On February 28, 2022, Celyad Oncology announced a voluntarily pause to the trial to further investigate 2 fatalities reported to have occurred in the study with similar pulmonary findings.² The product developer is currently evaluating any similar events in additional patients enrolled in the study.

“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 of Celyad Oncology, in a prior press release. “We are working diligently to better understand these events. In 25 patients previously treated with CYAD-101 in the alloSHRINK phase 1 trial [NCT03692429], which evaluated the TIM-based investigational candidate for the treatment of advanced mCRC, no dose-limiting toxicities [DLTs] were reported. Lastly, we anticipate no impact on our shRNA-based candidates, including CYAD-211, [which is] currently under investigation for the treatment of multiple myeloma.”

CYAD-101 is an investigational, non-gene edited allogeneic CAR T-cell therapy designed to co-express CAR based on NKG2D, which is expressed on natural killer cells that bind to NKG2DL that are expressed by a wide range of tumor cells and the inhibitory peptide TIM.³ TIM expression reduces signaling of the TCR complex by interfering with the CD3ζ component of the complex.

KEYNOTE-B79 enrolled patients with historically proven metastatic adenocarcinoma of the colon or rectum, an ECOG performance status of 0 or 1, and acceptable organ, hepatic, renal, pulmonary, and cardiac functions.⁴

Patients could not have received another investigational agent, device, or anticancer agent within 4 weeks of the first study treatment; filgrastim or similar growth factors within 7 days of the first study treatment; PD-1/PD-L1/PD-L2 agents or an agent directed to another stimulatory or co-inhibitory T-cell receptor; radiotherapy within 2 weeks before first study treatment; or a live vaccine within 30 days before first study treatment. Further, patients could not have a history of pneumonitis, or have undergone major surgery within 4 weeks prior to the first study treatment.

The primary outcome measures of the trial included occurrence of DLTs and objective response rate.

References

1. Celyad Oncology announces clinical hold of CYAD-101-002 phase 1b trial. News release. Celyad Oncology SA; March 2, 2022. Accessed March 2, 2022. https://bwnews.pr/3hzqpCV
2. Celyad Oncology announces voluntary pause of CYAD-101-002 phase 1b trial. News release. Celyad Oncology SA; February 28, 2022. Accessed March 2, 2022. https://bit.ly/3sAGXAZ
3. Celyad Oncology SA. Pipeline. Accessed March 2, 2022. https://bit.ly/3MhnKfy
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 August 5, 2021. Accessed March 2, 2022. https://clinicaltrials.gov/ct2/show/NCT04991948