Tecartus
brexucabtagene autoleucel
Species
no relevantMouse
Longest study
30 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 syngeneic mouse surrogate CAR-T only
“Since the anti-CD19 scFv utilised for KTE-X19 does only recognise human CD19, a murine surrogate model was engineered for non-clinical proof-of-concept studies in immune competent mice.”
Why that species
scFv recognizes only human CD19; no relevant animal model
“Similar as the pharmacology evaluation, also the non-clinical safety evaluation of KTE-X19 has been severely limited due to the lack of a relevant animal model.”
Surrogate molecule
Yes: anti-murine CD19 CAR (1D3 scFv) T cells in syngeneic lymphoma mice
“This surrogate model used an anti-murine CD19 CAR construct that was similar to KTE-X19 with the exception of the scFv, which has been derived from the 1D3 mAb recognizing murine CD19.”
Study lengthopen answer page →
Longest pivotal study
30 weeks
“lack of normal splenic B cells was observed 63 days, 143 days, and 209 days (the last time point examined) after anti-murine CD19 CAR T-cell infusion”
Pivotal GLP studies
None; no GLP tox. Safety assessed in surrogate syngeneic mouse pharmacology model plus vector integration site analysis
“Therefore, no GLP-compliant formal toxicology studies were performed.”
Route in tox
Intravenous (adoptive transfer in mice after 5 Gy TBI)
“Murine T cells were transduced with the anti-murine CD19 CAR construct and adoptively transferred into syngeneic mice which underwent TBI at 5 Gy for lymphodepletion”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (traditional); vector integration site analysis performed instead
“Traditional genotoxicity studies were not conducted using KTE-X19, however, given the use of a murine γ-retroviral vector to stably integrate the anti-CD19 CAR into the T cell genome, a risk associated with insertional mutagenesis exists.”
Carcinogenicity
Not conducted
“No carcinogencity/tumorigenicity studies were conducted.”
Reproductive & developmental
Not conducted (product characteristics, safety profile)
“No animal reproductive and developmental toxicity studies were conducted with KTE-X19, which is acceptable based on the product characteristics and safety profile.”
Safety pharmacology
Not conducted
“No secondary pharmacodynamics studies, safety pharmacology studies and pharmacodynamic drug interaction studies were conducted.”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
No NOAEL; surrogate mice showed prolonged B-cell aplasia (on-target/off-tumour) without overt toxicity
“Notably, this complete and prolonged absence of B cells was not accompanied by any evidence of overt toxicity.”
Risksopen answer page →
Immune & cytokine safety
CRS, neurotoxicity, MAS not investigated nonclinically; considered general CAR-T effects
“These toxic effects have also not been investigated in non-clinical studies which is fully acceptable considering that these effects are general effects of CAR T cells”
Biodistribution & persistence
No formal PK/biodistribution; surrogate CAR-T detected in spleen to ~1 week, not at Day 63
“Anti-murine CD19 CAR T cells were not detected in the spleens of treated mice at Day 63 after injection of CAR T cells; longer follow-up for anti-murine CD19 CAR T cells was not examined.”
Modality-specific risk
Insertional oncogenesis from gamma-retroviral vector (full-length LTRs); B-cell aplasia
“The combination of both the use of a γ-retroviral vector with full-length viral long terminal repeats (LTRs) and the high proliferative potential of the transduced T cells provides a certain risk of insertional oncogenesis”