Abecma
idecabtagene vicleucel · BCMA CAR-TCountry not stated; first-in-human dose-finding study in patients with relapsed/refractory multiple myeloma (CRB-401)
Tregzi: what was done before first-in-human, and what came after?
allogeneic Treg immunotherapy with HSPC and T cells (Orca-T) · Allogeneic Treg + HSPC + Tcon
Before first-in-human
First-in-human: where
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Repeat-dose tox before first-in-human
None; first clinical study supported by clinical safety data from a similar product instead of toxicology studies
“No toxicology studies were conducted for TREGZI. This omission is acceptable, as the applicant provided safety data from a Phase 1/2 clinical study with a similar clinical product to support initiation of the Phase 1b study”
First-in-human starting dose
No nonclinical basis; Phase 1/2 clinical safety data with a similar product supported the Phase 1b dose levels
“This omission is acceptable, as the applicant provided safety data from a Phase 1/2 clinical study with a similar clinical product to support initiation of the Phase 1b study”
Longest repeat-dose systemic studies
Longest repeat-dose study and recovery
No toxicology studies (no repeat-dose study); clinical data from a similar product used instead
“No toxicology studies were conducted for TREGZI. This omission is acceptable, as the applicant provided safety data from a Phase 1/2 clinical study with a similar clinical product to support initiation of the Phase 1b study”
Pivotal GLP studies
No toxicology studies; xenogeneic GVHD POC study OBS-24-001 (18 studies, sublethally irradiated immunodeficient mice, human Tcons +/- Tregs)
“No toxicology studies were conducted for TREGZI.”
DART package
Species: DART
Not conducted; not warranted based on product characteristics, biological activity and safety profile
“No genotoxicity, carcinogenicity, and developmental and reproductive toxicity (DART) studies were conducted for TREGZI. These studies are not warranted based on the product characteristics, biological activity, and safety profile.”
Reproductive & developmental
Not conducted
“No animal reproductive and developmental toxicity studies have been conducted with TREGZI to assess whether it can cause fetal harm when administered to a pregnant woman.”
PPND / ePPND: when
No DART studies; not warranted based on product characteristics, biological activity and safety profile
“No genotoxicity, carcinogenicity, and developmental and reproductive toxicity (DART) studies were conducted for TREGZI. These studies are not warranted based on the product characteristics, biological activity, and safety profile.”
Carcinogenicity
Species: carcinogenicity
Not conducted; not warranted
“No genotoxicity, carcinogenicity, and developmental and reproductive toxicity (DART) studies were conducted for TREGZI. These studies are not warranted based on the product characteristics, biological activity, and safety profile.”
Carcinogenicity model
Not conducted; omission acceptable given product characteristics, biological activity and clinical safety data
“No nonclinical studies were conducted to evaluate carcinogenicity/tumorigenicity of TREGZI. Given the characteristics and biological activity of TREGZI, together with the clinical safety data for TREGZI, this omission is acceptable.”
Carcinogenicity timing
Not required (not warranted based on product characteristics, biological activity and safety profile)
“No genotoxicity, carcinogenicity, and developmental and reproductive toxicity (DART) studies were conducted for TREGZI. These studies are not warranted based on the product characteristics, biological activity, and safety profile.”
Same question, other cell therapies
Carvykti
ciltacabtagene autoleucel · BCMA CAR-TCountry not stated; first clinical trial in patients with relapsed/refractory multiple myeloma (LEGEND-2)
MACI
autologous cultured chondrocytes on porcine collagen membrane · Autologous chondrocytesOutside the United States: all clinical studies ex-US (countries not named)
Tecelra
afamitresgene autoleucel · MAGE-A4 TCR-TCountry not stated; first-in-human dose-escalation and expansion study in HLA-A*02 patients with MAGE-A4-positive advanced tumors
Yescarta
axicabtagene ciloleucel · CD19 CAR-TCountry not stated; initial dose-finding study NCI 09-C-0082 in patients with advanced B-cell malignancies
Zemcelpro
dorocubicel · UM171-expanded cord blood CD34+Canada: dose de-escalation study (Study 001) at 2 sites in patients needing allogeneic stem cell transplant
Alofisel
darvadstrocel · Allogeneic adipose MSCNot stated in public reviews
Amtagvi
lifileucel · TIL therapyNot stated in public reviews
Aucatzyl
obecabtagene autoleucel · CD19 CAR-TNot stated in public reviews
Breyanzi
lisocabtagene maraleucel · CD19 CAR-TNot stated in public reviews
ChondroCelect
characterised viable autologous cartilage cells · Autologous chondrocytesNot stated in public reviews
Ebvallo
tabelecleucel · EBV-specific allogeneic T cellsNot stated in public reviews
Encelto
revakinagene taroretcel · CNTF (encapsulated RPE cell implant)Not stated in public reviews
Gintuit
allogeneic cultured keratinocytes and fibroblasts in bovine collagen · Allogeneic keratinocytes + fibroblastsNot stated in public reviews
Holoclar
autologous corneal epithelial cells containing limbal stem cells · Autologous limbal stem cellsNot stated in public reviews
Kymriah
tisagenlecleucel · CD19 CAR-TNot stated in public reviews
Lantidra
donislecel · Allogeneic pancreatic isletsNot stated in public reviews
Laviv
azficel-T · Autologous fibroblastsNot stated in public reviews
Omisirge
omidubicel · Expanded cord blood HPCNot stated in public reviews
Provenge
sipuleucel-T · PAP-GM-CSF (autologous APC)Not stated in public reviews
Rethymic
allogeneic processed thymus tissue · Allogeneic thymus tissueNot stated in public reviews
Ryoncil
remestemcel-L · Allogeneic BM-MSCNot stated in public reviews
Spherox
spheroids of autologous matrix-associated chondrocytes · Autologous chondrocyte spheroidsNot stated in public reviews
StrataGraft
allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen · Allogeneic keratinocytes + fibroblastsNot stated in public reviews
Tecartus
brexucabtagene autoleucel · CD19 CAR-TNot stated in public reviews
Zalmoxis
allogeneic T cells modified with HSV-TK / dLNGFR (nalotimagene carmaleucel) · HSV-TK suicide-gene T cellsNot stated in public reviews