Lynozyfic (linvoseltamab): how was the first human dose set?

Precedia/Multispecific antibodies/Lynozyfic/First dose

Lynozyfic: how was the first human dose set?

linvoseltamab · BCMA x CD3

First-in-human starting dose

Not stated in public reviews

Why it's blank

The public FDA and EMA reviews of Lynozyfic 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: 5-week: HNSTD 10 mg/kg/wk; 9/14-week: NOAEL not determined (early sacrifice at all doses; multi-organ inflammation, peritonitis/pleuritis, body weight loss) (EMA assessment report, p. 36)

Full method, every step sourced →

NOAEL / key findings

5-week: HNSTD 10 mg/kg/wk; 9/14-week: NOAEL not determined (early sacrifice at all doses; multi-organ inflammation, peritonitis/pleuritis, body weight loss)

“In the 9- or 14-week study, a NOAEL could not be determined.”

✓ VerifiedEMA assessment report, p. 36Source ↗

Summary across all 18 multispecifics →

Lynozyfic: how was the first human dose set?

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