Tecvayli
teclistamab
Species
MonkeyRabbit
Longest study
5 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
Cynomolgus monkey only (rabbit used for SC local tolerance only)
“The cynomolgus monkey was selected as the only pharmacologically relevant species for the nonclinical PK and toxicology assessments of teclistamab based on cross-species comparisons of sequence homology, relative target-binding affinities, and functional activity in cell-based assays.”
Why that species
Binds monkey CD3 and BCMA (BCMA ~36-fold lower affinity); no rodent CD3 binding, rabbit not expected to bind
“The parental CD3 monoclonal antibody did not bind rodent CD3, and teclistamab is not expected to bind rabbit CD3 or BCMA due to low sequence similarity; thus, the cynomolgus monkey was determined to be a pharmacologically relevant species for toxicology studies.”
Surrogate molecule
No surrogate; clinical molecule tested in monkey
“The toxicity and toxicokinetics (TK) of teclistamab were evaluated in a 5-week repeat-dose toxicity study in cynomolgus monkeys.”
Study lengthopen answer page →
Longest pivotal study
5 weeks
“The toxicity and toxicokinetics (TK) of teclistamab were evaluated in a 5-week repeat-dose toxicity study in cynomolgus monkeys.”
Pivotal GLP studies
GLP 5-week weekly IV monkey study (1, 10, 30 mg/kg) with 8-week recovery; 3-month study waived; rabbit SC local tolerance
“Monkeys were administered teclistamab (0 [control], 1, 10, or 30 mg/kg/dose, IV) once weekly for five total doses followed by an 8-week recovery period.”
Route in tox
IV in monkey (clinical route SC); single SC dose in rabbit for local tolerance
“This study evaluated the IV route of administration, whereas the clinical route of administration is subcutaneous (SC).”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (ICH S6(R1))
“Genotoxicity studies were not conducted with teclistamab.”
Carcinogenicity
Not conducted (ICH S9, advanced cancer)
“Carcinogenicity studies were not conducted with teclistamab.”
Reproductive & developmental
Not conducted; weight-of-evidence assessment (BCMA biology, knockout mice); no reproductive tissue findings in 5-week study
“No reproductive and developmental toxicity studies were conducted for teclistamab.”
Safety pharmacology
Incorporated into 5-week GLP monkey study (CV, respiratory, observational CNS); no effects
“Separate safety pharmacology studies were not conducted with teclistamab; however, the 5-week GLP study in cynomolgus monkey incorporated cardiovascular, respiratory as well as observational CNS assessments (body temperature and clinical signs).”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
NOEL 30 mg/kg/week (highest dose); no PD activity or adverse effects in monkey
“The no-observed-effect level for 5 weekly IV doses of teclistamab-treated monkeys was 30 mg/kg , the highest dose tested”
Risksopen answer page →
Immune & cytokine safety
ADA in 21/30 monkeys (7 with reduced exposure); in vitro whole-blood cytokine release of IL-8, IFN-γ, TNF-α
“Antidrug antibodies (ADAs) were detected in 21/30 teclistamab-treated animals, and seven of these animals exhibited lower teclistamab exposure after dosing on Day 22 or Day 29.”
Biodistribution & persistence
No distribution studies; IgG expected confined mainly to vascular space
“Due to its molecular size, teclistamab is expected to be primarily confined to the vascular space with only limited distribution to the extracellular space, which is typical for IgG-based mAbs.”
Modality-specific risk
Cytokine release/T-cell activation by MOA; monkey uninformative (low BCMA affinity, few target cells, ADA)
“Teclistamab is expected to cause cytokine release due to the mechanism of action (MOA).”