Ceylad said on Monday that it’s gotten promising early clinical results at the 3-month follow-up of the first dose-level in the solid tumor arm of the THINK trial (THerapeutic Immunotherapy with CAR-T NKR-2).
As the company said in its press release, at the first 3 x 108 cell dose-level administered to a total of three patients with metastatic cancer, the two colorectal cancer (mCRC) patients, who were progressing after at least two prior chemotherapy regimens, achieved a confirmed Stable Disease (SD) according to RECIST criteria at three months. According to recent studies conducted on similar patient populations, the company said, median progression free survival in these patients under standard of care is between 1.9 and 3.2 months. The third patient, a refractory pancreatic patient, was in progression at the same time point. Ceylad said that no toxicity signals were observed in any of the patients.
Christian Homsy, CEO of Celyad said: “We are pleased to have observed these encouraging preliminary results in such a late stage population. Despite being dosed only at a tenth of the expected efficacious dose based on animal experiments, the results show a stabilization of the disease. We look forward to the next stages of the trial.”
Dr. Frédéric Lehmann, Vice President Clinical Development and Medical Affairs at Celyad said: “These early results in the two heavily pre-treated mCRC patients are encouraging, considering the dismal clinical outcome of the existing standard of care for this refractory patient population. Based on these preliminary results, we look forward to progressing our clinical development plan, including higher doses and longer follow-up in the THINK study, as well at starting the SHRINK (CAR-T NKR-2 cells in combination with chemotherapy) and LINK (loco-regional administration) clinical trials shortly.”
Ceylad further said that patients in the second dose of the solid tumor arm (1 x 109) are currently being enrolled and treated. CAR-T NKR-2 cells have so far showed a safety profile that could allow an outpatient clinical approach.
The hematological cancer dose escalation arm, including relapsing/refractory Acute Myeloid Leukemia (AML) and Multiple Myeloma (MM) patients, is progressing. The first dose patients have been registered and are being treated with no toxicity signals to date.
Furthermore, the THINK trial, conducted in the US and in Europe, includes two stages: a dose escalation and an extension stage. Ceylad explained that the dose escalation is being conducted in parallel in solid cancers (colorectal, pancreatic, ovarian, triple negative breast and bladder) and in hematologic (AML and MM) cancer groups, while the extension phase will evaluate in parallel each tumor type independently.
According to Ceylad ,the dose escalation design includes three dose levels adjusted to body weight: up to 3×108, 1×109 and 3×109 NKR-2 CAR T-cells. At each dose, the patients receive three successive administrations, two weeks apart, of NKR-2 CAR T-cells at the specified dose.
NKR-2 CAR T-cell therapy was designed to act as a targeted therapy with short term persistence and multiple injections in order to provide a better controlled and more predictable safety profile. The primary objective is to avoid uncontrolled in vivo cell expansion and long-term persistence thereby replacing this paradigm with well controlled pharmacokinetics, Ceylad concluded.