Decnupaz (pivekimab sunirine): how was the first human dose set?

Precedia/Antibody-drug conjugates/Decnupaz/First dose

Decnupaz: how was the first human dose set?

pivekimab sunirine · CD123

First-in-human starting dose

Not stated in public reviews

Why it's blank

The public FDA and EMA reviews of Decnupaz 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 ADCs

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: FDA: no NOAEL in 13-week (thymic atrophy ≥0.01 mg/kg); single-dose max nonlethal 0.4 mg/kg; marrow, GI, skin, thymus (FDA multi-discipline review, p. 61)

Full method, every step sourced →

NOAEL / key findings

FDA: no NOAEL in 13-week (thymic atrophy ≥0.01 mg/kg); single-dose max nonlethal 0.4 mg/kg; marrow, GI, skin, thymus

“Adverse toxicity was observed at all doses since even the lowest tested dose of 0.01 Ab mg/kg produced thymic atrophy in males.”

✓ VerifiedFDA multi-discipline review, p. 61Source ↗

Summary across all 14 ADCs →

Decnupaz: how was the first human dose set?

Same question, other ADCs

Elahere

Enhertu

Kadcyla

Zynlonta

Adcetris

Besponsa

Datroway

Emrelis

Mylotarg

Padcev

Polivy

Tivdak

Trodelvy