Celyad ($CYAD) has posted data from a Phase I dose-escalation trial of its NKG2D CAR-T cells. None of the participants experienced objective responses at doses Celyad thinks are 50 times below efficacious levels, but the company sees the safety profile and short-term CAR-T cell persistence as positives as it heads deeper into development.
Mont-Saint-Guibert, Belgium-based Celyad gave its experimental therapy to 11 patients with either acute myeloid leukemia (AML) or multiple myeloma. The myeloma patients had undergone five or more lines of treatment, including at least one autologous stem cell-transplant, prior to enrolling in the study. Among the six participants with AML, the median proportion of immature white blood cells--myeloblasts--in the bone marrow was 50%.
Ten participants completed the 28-day assessment without dose-limiting toxicities. And no subjects experienced cytokine release syndrome, cell-related neurotoxicity, autoimmunity or CAR-T-related death. Two-fifths of participants suffered a toxicity of grade three or greater. Grade four adverse events included intracochlear bleed, neutropenia and thrombocytopenia. Celyad thinks the toxicities were linked to disease progression, not its therapy.
The safety data are one of the positives Celyad has taken away from the trial. The other relates to the persistence of the cell therapy. Celyad’s approach, which entails engineering T cells to express antigens found on natural killer cells, is designed to yield a therapy with a half-life more like a drug than rival CAR-Ts. Celyad thinks this will make it easier to predict and control the safety of its therapy. Data from the Phase I suggest the CAR-T cells will typically disappear within one week.
Celyad is now waiting for regulators on both sides of the Atlantic to approve the protocol for its next trial. The Phase I/IIa multiple dose trial will look for signs of clinical activity in seven types of solid and hematological cancer. This will provide an early hint of whether Celyad’s CAR-T cells work. The Phase I lacked objective responses to provide such a hint, although Celyad CEO Christian Homsy thinks the data contain cause for optimism. Homsy took to Twitter to make his case.
“We had two clinical responders at doses 100 times lower than expected and two more patients to be disclosed at ASH,” Homsey wrote.
The ASH abstract refers to a patient with p53-mutated AML with 50% myeloblasts at the start of the study who survived for four months. And another subject who entered partial response six months after treatment.