Epkinly
epcoritamab
Species
Monkey
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
“The nonclinical toxicity profile of epcoritamab was established in a series of nonclinical safety studies in cynomolgus monkeys, the only cross-reactive toxicology species.”
Why that species
Similar affinity for human and monkey CD3/CD20; no binding to dog, pig, rat, mouse CD20; CD3 not expected in other species
“The epcoritamab binding data indicates that among the species tested, the cynomolgus monkey is the only pharmacologically relevant species for toxicology studies.”
Surrogate molecule
No surrogate; clinical molecule tested in monkey
“We agree that the cynomolgus monkey is a pharmacologically relevant nonclinical species to assess the toxicity of epcoritamab, and general toxicology studies in other species are not warranted.”
Study lengthopen answer page →
Longest pivotal study
5 weeks
“The toxicity and toxicokinetics (TK) of epcoritamab were evaluated in a 5-week toxicity study in cynomolgus monkeys.”
Pivotal GLP studies
GLP 5-week monkey study (weekly IV, single IV, monthly SC) with 6-week recovery; 3-month study waived (ADA)
“Study: A 5-Week Toxicity Study of GEN3013 by Intravenous Infusion and Subcutaneous Injection in Cynomolgus Monkeys with Bioavailability, Local Tolerance, and a 6 Week Recovery Period / 503484 / eCTD location 4.2.3.2”
Route in tox
IV infusion (weekly or single) and SC injection (Days 1 and 29)
“Monkeys were administered epcoritamab as a once weekly (QW x 5) IV infusion (0 [control], 0.01, 0.1, or 1 mg/kg), a single IV infusion (0.1 or 1 mg/kg), or a once monthly (Days 1 and 29) subcutaneous (SC) injection (0.1, 1, or 10 mg/kg).”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (ICH S6(R1), ICH S9)
“Genotoxicity studies were not conducted for epcoritamab per ICHS6(R1) and ICH S9 guidance.”
Carcinogenicity
Not conducted (ICH S6(R1), S1A, S9)
“Carcinogenicity studies were not conducted for epcoritamab per ICHS6(R1), ICH S1A, and ICH S9 guidance.”
Reproductive & developmental
Not conducted; EFD waived due to monkey immunogenicity; WOE assessment; no reproductive organ findings in 5-week study
“An EFD toxicity study of epcoritamab in cynomolgus monkeys was waived for phase 3 trials and registration of epcoritamab across ICH regions (FDA, EMEA, and PMDA) given the high potential for immunogenicity of epcoritamab in cynomolgus monkeys.”
Safety pharmacology
Incorporated into pivotal 5-week monkey study (CNS, respiratory, CV)
“No specific safety pharmacology studies have been conducted with epcoritamab.”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
NOAEL 0.1 mg/kg IV, 10 mg/kg SC; cytokine-related clinical signs, one death at 1 mg/kg IV; lymphoid depletion
“In the pivotal 5-week study (503484), the NOAEL in the IV repeat dosing group was 0.1 mg/kg, while the NOAEL in the SC dosing group was 10 mg/kg.”
Risksopen answer page →
Immune & cytokine safety
Dose-dependent first-dose cytokine release (lower with SC); strong neutralizing ADA at ≤0.1 mg/kg IV
“Dose-dependent increases in the plasma cytokines IL-2, IL-6, IL-8, IL-10, IL-15, IFN-γ, TNF-α, and MCP-1 were observed in all epcoritamab-treated groups after the first dose.”
Biodistribution & persistence
No ADME studies; target-mediated drug disposition; SC bioavailability 85% (males) / 49% (females)
“Epcoritamab displayed a clear pattern of target-mediated drug disposition, with faster clearance of drug at low doses compared with high doses.”
Modality-specific risk
First-dose cytokine release (CRS-like signs, mortality at ≥1 mg/kg IV); SC dosing lowered Cmax and cytokine peaks
“These findings were considered associated with elevated cytokine levels, primarily following the first dose.”