CAR-T, FDA

FDA gives Cellectis a green light to relaunch off-the-shelf CAR-T studies — with several strings attached

Two months after the FDA forced Cellectis $CLLS to hit the brakes on a pair of clinical trials for their off-the-shelf CAR-T UCART123, regulators have followed up with a green light to resume testing. But they’re adding some key safety measures to try to reduce any outstanding risks for patients in these high profile studies.

Cellectis CEO André Choulika

The trial halt came on the death of the first patient dosed with UCART123. Now investigators can begin again. But there are some extraordinary strings that are now attached:

  •  The cohort dose level has been limited to 6.25×104 UCART123 cells/kg.
  • Enrollment has to be staggered, with a 28-day gap between enrollment of 2 patients in the 2 studies, evidently to better control how many patients are exposed to risk.
  • The cyclophosphamide dose of the lympho-depleting regimen — for prepping patients — has been reined in to 750 mg/m²/day over three days with a maximum daily dose of 1.33 grams of cyclophosphamide.
  • Regulators want to make sure there’s no uncontrolled fever after lymphodepletion.
  •  The next three patients in each protocol has to be under 65 years of age.

Share of Cellectis, helmed by CEO André Choulika, shot up 24%.

Paris-based Cellectis was forced into a halt back on September 4, after a patient died on the launch of trials for acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm.

The last time there was a trial halt in CAR-T, the FDA waited just days to give Juno Therapeutics a signal to get their study for JCAR015 relaunched, only to see several of the next set of patients die. That first halt came with no new limits aside from a restriction on the treatment regimen used to prep patients for a personalized CAR-T. The second halt led to the elimination of JCAR015 as a viable drug candidate.

While the first generation of personalized CAR-T drugs using patients’ cells has been beset from the beginning with signs of cytokine release syndrome and neurotoxicity, regulators and developers have grown steadily more confident of their ability to screen patients and lower risks. Cellectis, which is using a new approach to develop universal CAR-T drugs that can attack liquid cancers, has a whole new set of demands to meet as investigators look for the next big step forward in the field.

And they’ll be scrutinized every step of the way back.



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