Epkinly (epcoritamab): what was done before first-in-human, and what came after?

Precedia/Multispecific antibodies/Epkinly/Tox package

Epkinly: what was done before first-in-human, and what came after?

epcoritamab · CD20 x CD3

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

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.

First-in-human starting dose

Not stated in public reviews

Why it's blank

The public FDA and EMA reviews of Epkinly don't say how the first human dose was chosen. That rationale is in the IND, which is confidential, so it is missing for most approved products.

How it's usually set for multispecifics

ADCs with cytotoxic payloads follow the S9 rules (1/10 STD10 or 1/6 HNSTD of the ADC, scaled by body surface area). For immune agonists, a MABEL-based start dose should be considered instead.

“For example, for cytotoxic payloads, the starting clinical dose can be determined using either 1/10th the Severely Toxic Dose (STD) in 10% of animals (STD10) in rodents or 1/6th the Highest Non- Severely Toxic Dose (HNSTD) in non-rodents, for the ADC based on body surface area, depending on which is the most appropriate and/or sensitive species.”

✓ VerifiedICH 2018: ICH S9 Guideline: Nonclinical Evaluation for Anticancer…, p. 15Source ↗

This product's starting point

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 (EMA assessment report, p. 36)

Full method, every step sourced →

Longest repeat-dose systemic studies

Longest repeat-dose study and recovery

5-week IV/SC cynomolgus monkey study with 6-week recovery

“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”

✓ VerifiedFDA multi-discipline review, p. 53Source ↗

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”

✓ VerifiedFDA multi-discipline review, p. 53Source ↗

DART package

Species: DART

Not conducted; monkey EFD study waived due to high immunogenicity in cynomolgus monkeys; weight-of-evidence assessment

“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.”