Spiegel Discusses the Phase 2 Study Evaluating CRG-022 in R/R LBCL

Jay Spiegel, MD, assistant professor at the University of Miami Health System, discusses what led to the initiation of a phase 2 study (NCT05972720) evaluating CRG-022 (firicabtagene autoleucel; firi-cel), a CD22-directed autologous chimeric antigen receptor (CAR) T-cell therapy, for the treatment of patients with relapsed/refractory large B-cell lymphoma following treatment with CD19-directed CAR T-cell therapy.

The prospective, open-label, multicenter trial is assessing the safety, tolerability, efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of CRG-022 in this patient population.

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0:09 | This is a single-arm, phase 2 study for the purposes of registration testing firi-cel or CRG-022, which is a CD22-targeting CAR in relapsed/refractory diffuse large B-cell lymphoma. The primary end point is overall response rate and the secondary end points are progression-free and overall survival.

0:36 | So far, we are just talking about a trial that is in progress. Phase 2 is supposed to enroll 100 patients total, and about 20 patients have been enrolled to date. This is based on a phase 1 single institution study that I was a part of as a fellow at Stanford, where we tested the same CAR in patients with relapsed diffuse large B-cell lymphoma. Thirty-eight patients were treated.

1:09 | When you think about the kind of classic CAR T [adverse] effects, there was CRS, which was relatively common, but low grade, and neurotoxicity [which was] pretty uncommon, at least relative to axi-cel, severe neurotoxin with less than 5%, and this was typically managed with steroids or tocilizumab. The 1, I would say, relatively unique toxicity with this CAR that is different from other CARs is the incidence of [immune effector cell associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS)], which occurred at the higher dose level that we tested in about 1/3 of patients. That actually led us to reduce the dose to 1 million CARs per kg, which is the dose that was taken forward to phase 2. And in those patients, that happened about 10% of the time. That is something that in some cases required prolonged steroids and some other additional agents. The phase 1 study just was accepted for publication in the Lancet, so should be coming out pretty soon.