Carvykti
ciltacabtagene autoleucel
Species
no relevantMonkeyMouse
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; NCG mouse xenografts, non-GLP NHP pilot with autologous NHP CAR-T
“Therefore, animal studies evaluating the safety profile of CARVYKTI™ were limited due to lack of a pharmacologically relevant animal species.”
Why that species
Binding domain does not bind mouse or NHP BCMA
“In vitro data indicate that does not significantly bind to recombinant mouse or NHP BCMA expressed on cells.”
Surrogate molecule
Yes: autologous cynomolgus T cells transduced with the CAR vector (non-GLP pilot)
“NHP cilta-cel was manufactured from autologous Cynomolgus monkey peripheral blood samples following a similar manufacturing method that would be used for human T cells.”
Study lengthopen answer page →
Longest pivotal study
14 weeks
“Scheduled Sacrifice Time Points Day 98”
Pivotal GLP studies
No GLP tox; non-GLP cynomolgus pilot (n=2, single IV, 30 days) plus NCG mouse xenograft studies
“The applicant performed one in vivo non-GLP toxicology pilot study in Cynomolgus monkeys using autologous CAR-T cells manufactured with the second/ third generation hybrid LV developed by Legend.”
Route in tox
Intravenous infusion (after cyclophosphamide in NHP)
“The NHPs were infused with cyclophosphamide (22.3 mg/kg) on Day -3, followed by IV infusion of the CAR T cells on Day 0.”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (classical); lentiviral integration site analysis instead
“No classical genotoxicity studies have been performed.”
Carcinogenicity
Not conducted (ICH S9; no mouse BCMA cross-reactivity)
“As indicated in the ICH S9 guidance, carcinogenicity studies are not warranted to support marketing for therapeutics intended to treat advanced cancer.”
Reproductive & developmental
Not conducted; binding domain not detected in human reproductive organs
“Therefore, traditional DART studies were not conducted.”
Safety pharmacology
Not conducted (targeting domain does not bind mouse BCMA)
“The absence of safety pharmacology studies is therefore, acceptable.”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
No NOAEL; NHP 5 and 40x10^6 cells/kg: no adverse effects, transient mild blood count decreases
“There were no test article-related adverse effects on survival, clinical signs, body weights or body temperatures.”
Risksopen answer page →
Immune & cytokine safety
CRS, TLS, MAS not investigated nonclinically; off-target CLDN9 binding seen only on overexpressing cells
“These toxic effects have not been investigated in non-clinical studies which is acceptable considering that these effects are general effects of CAR T cells”
Biodistribution & persistence
No biodistribution studies; mouse CAR copies peaked ~Day 34-35, baseline by Day 48
“No biodistribution studies with JNJ-68284528 were conducted.”
Modality-specific risk
Insertional oncogenicity from lentiviral integration; off-target claudin-9 binding
“Based on this study, the risk of insertional oncogenicity is expected to be very low.”