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

Precedia/Monoclonal antibodies/Unloxcyt/Tox package

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

cosibelimab · PD-L1

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 Unloxcyt 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 monoclonal antibodies

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 100 mg/kg once weekly (highest dose) in 13-week monkey study (FDA multi-discipline review, p. 55)

Full method, every step sourced →

Longest repeat-dose systemic studies

Longest repeat-dose study and recovery

13-week cynomolgus monkey (once-weekly IV slow bolus) with 10-week recovery

“CK-301: Once Weekly Intravenous Slow Bolus Injection Toxicity and Toxicokinetic Study in Cynomolgus Monkeys for 13 Weeks with a 10-Week Recovery Phase”

✓ VerifiedFDA multi-discipline review, p. 55Source ↗

Pivotal GLP studies

GLP 4-week and 13-week repeat-dose studies in cynomolgus monkeys, once-weekly IV slow bolus, 10-week recovery for 13-week study

“CK-301: Once Weekly Intravenous Slow Bolus Injection Toxicity and Toxicokinetic Study in Cynomolgus Monkeys for 13 Weeks with a 10-Week Recovery Phase”

✓ VerifiedFDA multi-discipline review, p. 55Source ↗

DART package

Species: DART

Not conducted; literature-based risk assessment instead

“A literature-based risk assessment of developmental and reproductive risk was conducted in lieu of performing developmental and reproductive toxicology studies.”