Breyanzi
lisocabtagene maraleucel
Species
no relevantMouse
Longest study
14 wk
Genotox
Not conducted Not conducted
Carcinogenicity
Not conducted Not conducted
Repro
Not conducted Not conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
No relevant species; in vitro and NSG mouse xenograft only
“In particular, suitable animal models are not available for accurately assessing the non-clinical characteristics of a human cell-based product such as JCAR017.”
Why that species
FMC63 scFv binds human CD19 only; no mouse or NHP cross-reactivity
“The results support that JCAR017 is specific for human CD-19 binding and lacks species cross-reactivity, in particular towards mouse and non-human primate.”
Surrogate molecule
No surrogate; human product tested in immunodeficient xenograft mice
“The lack of conventional in vivo studies and the use of immune-deficient Raji Burkitt’s lymphoma-bearing NOD/SCID IL-2Rγnull mice model are justified and appropriate to investigate autologous cell-based products.”
Study lengthopen answer page →
Longest pivotal study
14 weeks
“periods (0-100 days), in contrast with the control group (died by day 10-11).”
Pivotal GLP studies
None; traditional single/repeat-dose, genotox, carcinogenicity, DART and local tolerance studies not conducted
“In this light, traditional toxicity, including single and repeat-dose toxicity, genotoxicity, carcinogenicity, reproductive and developmental toxicity, and local tolerance studies were deemed of negligible utility and thus were not conducted.”
Route in tox
Intravenous (xenograft pharmacology)
“JCAR017 is an autologous cell-based product administered by intravenous infusion.”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (traditional); lentiviral integration site mapping instead
“Traditional genotoxicity assays and carcinogenicity assessments were not performed for JCAR017.”
Carcinogenicity
Not conducted (ICH S9); GLP in vitro 60-day IL-2-independent growth study instead
“Consistent with regulatory guidance under “Nonclinical Evaluation for Anticancer Pharmaceuticals” (ICH S9, 2009) carcinogenicity studies were not conducted.”
Reproductive & developmental
Not conducted (no survival in immunocompetent rodents; GvHD in immunodeficient mice)
“JCAR017 does not survive in immunocompetent rodents and induces graft-versus-host disease in immunocompromised mice; therefore, traditional DART studies were not conducted.”
Safety pharmacology
Not conducted (no species cross-reactivity)
“The autologous cell-based JCAR017 T products lack species cross-reactivity thus in all NC studies performed safety pharmacology was deemed not practical and of negligible utility.”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
No NOAEL; long-term safety in animals limited; tissue cross-reactivity showed off-target recognition of low concern
“Animal studies to assess the long-term safety of JCAR017 were limited because the JCAR017 does not survive in immunocompetent rodents and induces graft-versus-host disease in immunocompromised mice.”
Risksopen answer page →
Immune & cytokine safety
In vitro CD19-specific IFN-γ, IL-2, TNF-α release; EGFRt allows cetuximab-mediated CAR-T depletion
“These data provide support for administration of commercially available antibodies targeting the truncated EGFR domain on the surface of JCAR017 to reduce/eliminate the CAR T cells in vivo, if necessary.”
Biodistribution & persistence
No biodistribution studies; persistence assessed in xenograft PD study
“No biodistribution studies with JCAR017 were conducted.”
Modality-specific risk
Insertional mutagenesis/oncogenic transformation from lentiviral transduction; no preferential integration found
“The risk of insertional mutagenesis with lentiviral transduction of the T cells, leading to malignant transformation, was studied using unbiased, genome-wide bioinformatics methods.”