Amtagvi
lifileucel
Species
no relevantMouse
Longest study
none
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 animal studies with product; published murine and human TIL literature only
“No nonclinical studies were conducted with AMTAGVI. Instead, the applicant cited published nonclinical data evaluating similar murine and human tumor-derived T lymphocytes to provide support for AMTAGVI.”
Why that species
Omission of tox studies accepted given product characteristics and biological activity (autologous unmodified T cells)
“No toxicology studies were conducted for AMTAGVI. Given the characteristics and biological activity of AMTAGVI, this omission is acceptable.”
Surrogate molecule
Yes: published studies of similar murine (homologous) and human TILs used in lieu of product testing
“Instead, the applicant cited published nonclinical data evaluating similar murine and human tumor-derived T lymphocytes to provide support for AMTAGVI.”
Study lengthopen answer page →
Longest pivotal study
0 (no in vivo tox study)
“No toxicology studies were conducted for AMTAGVI.”
Pivotal GLP studies
None; five published pharmacology papers (TIL prognosis, expansion, cytotoxicity, murine tumor models) submitted in Module 4
“No nonclinical pharmacology studies were performed for AMTAGVI.”
Route in tox
Not applicable; no in vivo studies with product
“No nonclinical studies were conducted with AMTAGVI.”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (not warranted given product characteristics and biological activity)
“No genotoxicity studies were conducted for AMTAGVI. Given the characteristics and biological activity of AMTAGVI, this omission is acceptable.”
Carcinogenicity
Not conducted (expanded TILs free of tumor cells; residual tumor cell release controls; no clinical tumorigenicity signal)
“No tumorigenicity studies were conducted for AMTAGVI. This is acceptable since Studies #3 and #4 provided evidence that the expanded human TIL cultures in the studies were free of tumor cells.”
Reproductive & developmental
Not conducted (product characteristics and biological activity)
“No DART studies were conducted for AMTAGVI. Given the characteristics and biological activity of AMTAGVI, this omission is acceptable.”
Safety pharmacology
Not conducted; omission accepted
“No safety pharmacology studies were conducted for AMTAGV1. Given the characteristics and biological activity of AMTAGVI, this omission is acceptable.”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
No NOAEL; no toxicology studies; no target-organ findings available
“No toxicology studies were conducted for AMTAGVI. Given the characteristics and biological activity of AMTAGVI, this omission is acceptable.”
Risksopen answer page →
Immune & cytokine safety
No immunotox/cytokine studies; literature shows anti-CD3-activated TIL cytotoxicity specific to autologous tumor, not heterologous targets
“Compared to TILs expanded in 1000 U/ml of IL-2 alone, TILs activated with anti-CD3 + 50 U/ml of IL-2 demonstrated higher cytotoxicity against autologous tumor cells but not against Daudi, K562, or histologically matched heterologous tumor cells.”
Biodistribution & persistence
Not conducted; accepted based on known distribution of IV T cell products
“No nonclinical studies were conducted to evaluate distribution of AMTAGVI. Based on the available information on the in vivo distribution of intravenously administered T cell products, this omission is acceptable.”
Modality-specific risk
Residual tumor cell contamination/tumorigenicity of tumor-derived product; LD chemo and IL-2 toxicity deferred to approved labels
“AMTAGVI specifications also include measures to control residual tumor cell levels in the final drug product.”