Allogeneic CAR T-cell therapy safe, clinically active in metastatic colorectal cancer
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An allogeneic chimeric antigen T-cell therapy showed evidence of clinical activity among patients with metastatic colorectal cancer, according to results of a dose-escalation study presented at Gastrointestinal Cancers Symposium.
No patients treated so far in the trial have experienced a serious adverse event or developed graft-versus-host disease, according to the study investigators.
CYAD-101 (Celyad) is an investigational, non-gene edited allogeneic CAR T-cell therapy that targets the natural killer group 2D ligand (NKG2DL). The CAR co-expresses a T-cell receptor (TCR) inhibitory peptide, which interferes with signaling by the endogenous TCR to prevent GVHD, according to the manufacturer.
“CAR T cells have shown clinical efficacy in patients with advanced B-cell malignancies but, to date, have failed to deliver a clinically relevant impact on solid tumor indications,” Hans Prenen, MD, PhD, deputy head of the oncology department at University Hospital Antwerp in Belgium, said during his presentation. “Furthermore, clinical-grade manufacturing of autologous CAR T cells has inherent operational and medical limitations that allogeneic CAR T cell products — whereby cells from healthy donors are used to generate an off-the shelf-product — could overcome.”
Prenen and colleagues evaluated the safety and optimal dose of CYAD-101 produced from a single donor among patients with unresectable metastatic colorectal cancer as part of the phase 1 alloSHRINK study. The study included patients with relapsed or refractory disease who experienced progression after treatment with oxaliplatin-based chemotherapy, with or without irinotecan-based chemotherapy.
Patients received three infusions of CYAD-101 at one of three dose levels: 1 × 108, 3 × 108 or 1 × 109 T cells per infusion. Each infusion was preceded by standard FOLFOX preconditioning chemotherapy.
Fifteen patients had been treated in the study at the time of data reporting.
Results showed two patients had a partial response to therapy, including one patient with KRAS-mutant disease. Nine patients had stable disease, including seven with stable disease lasting 3 months or longer.
Among the nine patients who received the highest dose of CYAD-101, six had some evidence of tumor control according to RECIST version 1.1 criteria.
Investigators chose the highest dose level of 1 × 109 T cells per infusion as the recommended dose for subsequent studies.
Median PFS was 3.9 months (range, 1.2-8.1). Median OS was 10.58 months (range, 1.9-18.7)
Safety results showed no dose-limiting toxicities, grade 3 or greater adverse events or GVHD associated with CYAD-101 infusions.
“Our observations imply that modulation of the endogenous immune response may be an important mechanism of action of CYAD-101 in [patients with metastatic colorectal cancer],” Prenen said. “Further testing will be pursued in the ongoing expansion phase of the alloSHRINK clinical study to confirm our findings.”
Prenen also said there are plans to evaluate the clinical effectiveness of CYAD-101 in combination with other immunotherapies — including immune checkpoint inhibitors — in the KEYNOTE-B79 study, which is set to begin enrolling patients with refractory metastatic colorectal cancer later this year.
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Prenen H, et al. Abstract 74. Presented at: Gastrointestinal Cancers Symposium (virtual meeting); Jan. 15-17, 2021.
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