The FDA has lifted the clinical hold it placed on Cellectis’ CAR-T trials in September following the death of a patient. Cellectis is now a step closer to restarting enrollment in the studies yet faces new restrictions that will cap how quickly it gets back up to speed.
Following the recommendation of the data monitoring committee, Cellectis has agreed to drop the dose of its allogeneic CD123 CAR-T UCART123 and that of the cyclophosphamide used in the lympho-depleting regimen. Other changes include the capping of the maximum age of the next three patients at 65 years—an action Cellectis foreshadowed in comments about the wisdom of enrolling a 78-year-old in the trial—and the addition of new day 0 inclusion/exclusion criteria.
Many of the changes were predictable based on comments from Cellectis and the data monitoring committee, plus precedents from previous clinical holds. Fewer people saw the requirement for staggered enrollment across the acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN) trials coming, though.
The stipulation will see Cellectis stagger enrollment across the two phase 1 clinical trials in which it is testing the CAR-T. Cellectis must leave at least 28 days between the enrollment of patients in either study. That precaution gives investigators, Cellectis and the FDA a window in which to assess whether patients treated under the revised protocol are at risk of severe cytokine and capillary leak syndromes, the adverse events that affected the two subjects treated in the trial to date.
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Jefferies analyst Biren Amin also noted one change Cellectis and the FDA opted against making.
“Surprisingly, one potential change that was not implemented was requiring tumor debulking agents which would potentially control the magnitude of T-cell expansion,” Amin wrote in a note to investors.
Overall, the lifting of the clinical hold and protocol changes were seen positively by investors, sending Cellectis’ stock up 18% in after-hours trading. Those gains partly offset losses suffered over the past week in the wake of the publication of abstracts for the upcoming ASH Annual Meeting and Exposition. The stock was above its preclinical hold level before the recent sell-off.
Cellectis will now seek IRB clearance for the revised protocol before resuming enrollment in the AML and BPDCN clinical trials, which between them plan to to treat more than 200 people with the off-the-shelf CAR-T.
Results in those patients will dictate whether the changes mark the start of a brighter future for UCART123. Or, as happened with Juno after it made its considerably quicker exit from clinical hold, the resumption of the study proves to be a temporary reprieve for the CAR-T.