The decision comes after a previous clinical hold delayed key medical milestones in the KEYNOTE-B79 trial.
This content originally appeared on our sister site, OncLive.
Celyad Oncology is no longer developing its investigational chimeric antigen receptor (CAR) T-cell therapy CYAD-101 for the treatment of unresectable metastatic colorectal cancer (mCRC).1
The program was previously put on clinical hold by the FDA in March 2022 due to insufficient information to evaluate risk to study participants and the phase 1b CYAD-101-002 trial (KEYNOTE-B79; NCT04991948) voluntarily paused in February 2022 to investigate 2 deaths.2 The hold was lifted in August 2022.3
No new safety concerns have led to the discontinuation, rather, Celyad stated that the decision was based on strategic, financial, and medical review, accounting for the costs associated with the development program and the delays in reaching key medical milestones due to the prior hold.
The trial was evaluating CYAD-101 with concurrent FOLFOX (leucovorin, 5-fluorouracil, and oxaliplatin) and followed by pembrolizumab (Keytruda) in patients with unresectable mCRC. Although the development of CYAD-101 has been discontinued, all patients currently enrolled in CYAD-101 trials will continue to receive their protocol-defined follow-up.
CYAD-101 was an investigational, non-gene edited allogeneic CAR T-cell product engineered to co-express the CAR based on NKG2D, which is expressed on natural killer cells and binds to lymphocyte receptor NKG2DL. NKG2DL is expressed on a wide range of tumor cells, as well as the inhibitory peptide TIM.4 TIM expression reduces signaling of the TCR complex by interfering with the CD3ζ component of the complex.
The evaluation of CYAD-211, an allogeneic short hairpin RNA (shRNA)–based, anti-BCMA CAR T-cell therapy for the treatment of relapsed/refractory multiple myeloma, will continue in the phase 1 IMMUNICY-1 trial (NCT04613557), according to the press release. The ongoing IMMUNICY-1 trial is investigating treatment of CYAD-211 following preconditioning with cyclophosphamide and fludarabine in patients with relapsed/refractory multiple myeloma.
CYAD-211 is engineered to co-express a BCMA CAR and a single shRNA hairpin, which interferes with the expression of the CD3ζ component of the TCR complex.4