Talvey
talquetamab
Species
Monkey
Longest study
4 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 (tool molecule for pivotal tox); no rodent tox
“Toxicology studies were not conducted in rodents due to the lack of talquetamab or JNJ-64024701 cross reactivity in these species.”
Why that species
Talquetamab binds cyno CD3 but not cyno GPRC5D (~100-fold lower activity); tool molecule binds cyno GPRC5D and CD3
“Due to the lack of cross reactivity of talquetamab to cynomolgus monkey GPRC5D, the tool molecule (JNJ-64024701) was developed.”
Surrogate molecule
Yes: monkey-cross-reactive GPRC5DxCD3 tool molecule JNJ-64024701 (same CD3 arm, different GPRC5D arm)
“The tool molecule has the same CD3 binding arm but different GPRC5D binding arm as talquetamab, and binding and in vitro functional activity against cGPRC5D-expressing cells consistent with talquetamab against hGPRC5D-expressing cells.”
Study lengthopen answer page →
Longest pivotal study
4 weeks
“The toxicity and toxicokinetics (TK) of JNJ-64024701 were evaluated in a GLP-compliant 1-month repeat”
Pivotal GLP studies
1-month GLP IV study of tool molecule in cynomolgus monkey (0, 10, 30 mg/kg weekly x4); non-GLP 4-week talquetamab tolerability study
“JNJ-64024701 (GCDB32 GPRC5DxCD3): A 1-Month GLP Intravenous Toxicity and Toxicokinetic Study in Cynomolgus Monkeys / Study T-2017-009”
Route in tox
IV in monkey tox (clinical route SC); SC local tolerance in rabbit
“This study evaluated the IV route of administration, whereas the intended clinical route of administration is SC injection.”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (ICH S6; biotechnology-derived product)
“Genotoxicity studies routinely conducted for pharmaceuticals have not been conducted and are not applicable to biotechnology-derived pharmaceuticals such as talquetamab per ICH S6.”
Carcinogenicity
Not conducted (ICH S9; advanced cancer)
“As indicated in the ICH S9 guidance, carcinogenicity studies are not warranted to support marketing for therapeutics intended to treat patients with advanced cancer.”
Reproductive & developmental
Not conducted (weight-of-evidence assessment; ADA limits exposure, no relevant species); reproductive organs examined in repeat-dose study
“We agree with the Applicant’s WOE-based approach for the assessment of reproductive and developmental toxicity.”
Safety pharmacology
Incorporated into 1-month GLP monkey study with tool molecule (CV, respiratory, CNS); no effects
“However, cardiovascular, respiratory, and observational CNS safety pharmacology endpoints were incorporated into the 1-month GLP repeat dose toxicity study conducted with the tool molecule in cynomolgus monkeys”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
No adverse effects up to 30 mg/kg weekly (highest dose); transient lymphocyte decrease, increased globulins, fibrinogen, IL-10
“No adverse effects on any toxicology or safety pharmacology parameter evaluated at up to the high dose of 30 mg/kg weekly”
Risksopen answer page →
Immune & cytokine safety
In vitro dose-dependent cytokine release (IL-6, IFN-g, TNF-a etc.); ADAs in 10/12 monkeys reduced exposure
“Antidrug antibodies (ADAs) were observed in 10/12 JNJ-64024701-treated monkeys, and ADA-positive animals exhibited decreased JNJ-64024701 exposure following repeated doses.”
Biodistribution & persistence
No distribution studies; IgG-like, confined mainly to vascular space; monkey half-life 9-12 days
“Traditional distribution studies were not conducted for talquetamab, which is an antibody with a molecular weight of 147 kDa.”
Modality-specific risk
On-target/off-tumor toxicity (GPRC5D in skin, hair follicles, tongue) and T-cell activation/cytokine release
“the purpose of this study was to assess the potential on-target/off-tumor toxicity of a CD3xGPRC5D bsAb.”