Cellectis SA said the FDA has placed a clinical hold on a phase I study of UCART-CS1A, an allogenic CAR T-cell therapy it has been testing in patients with relapsed or refractory multiple myeloma, after one person enrolled in the study died from a case of treatment-emergent cardiac arrest.
Cellectis' chief medical officer, Carrie Brownstein, told BioWorld she supported the move, which formalized a decision she'd already taken with her team. "The best way to protect this potentially life-changing treatment, which I still strongly believe in, is to learn from what happened and understand it and adjust our studies to ensure that we're monitoring and mitigating for whatever it was that may have happened so that we can move forward," she said.
U.S.-listed shares of the Paris-based biotech (NASDAQ:CLLS) fell 14.3% on July 7 to close at $16.32.
The study, called MELANI-01, was designed as an open-label dose-escalation study. It's evaluating three doses of UCART-CS1A, an allogeneic, off-the-shelf, gene-edited T-cell candidate for the treatment of CS1/SLAMF7-expressing hematologic malignancies. Five patients have been enrolled to date, including the one who died. That individual had numerous lines of prior therapy, including autologous CAR T cells, the company said.
"This was an unexpected turn of events in the patient, who was actually doing much better at the time," Brownstein said. In the end, he had signs and symptoms consistent with cytokine release syndrome, but it's too early to determine exactly what happened, she said, calling it an evolving situation.
The man was the first and only participant in the study to receive dose level two of UCART-CS1A, or 3 million cells/kg. The other participants so far have all received dose level one, comprising 1 million cells/kg.
Generally speaking, the FDA has 30 days to provide the sponsor of an affected trial with an official list of deficiencies that triggered the hold. Sponsors then respond with a draft proposal of how to deal with the deficiencies. "My goal," Brownstein said, "is to be more proactive." Her team already started developing a risk mitigation plan prior to being notified of the hold.
Cellectis' team has decided to expand enrollment of patients at dose level one, "which may be the appropriate dose for further evaluation in the expansion portion of the trial and potentially the recommended phase II dose based on an assessment of the preliminary clinical and translational data," the company said.
Meanwhile, patient enrollment is ongoing in two other phase I dose-escalation trials: AMELI-01 evaluating UCART-123 in relapsed and refractory acute myeloid leukemia and BALLI-01 evaluating UCART-22 in relapsed and refractory B-cell acute lymphoblastic leukemia.