Lunsumio
mosunetuzumab · CD20 x CD3US, Republic of Korea, Canada: dose-escalation part (Group A) of study GO29781 in patients with R/R B-cell NHL
Elrexfio: what was done before first-in-human, and what came after?
elranatamab · BCMA 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 Elrexfio 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.”
This product's starting point
NOAEL / key findings: No NOAEL in 3-month SC study (immunosuppression, infections, moribundity at all doses); NOAEL 0.3 mg/kg/wk in 1-month studies (FDA multi-discipline review, p. 58)
Longest repeat-dose systemic studies
Longest repeat-dose study and recovery
3-month (13-week) SC cynomolgus monkey study (14 weekly doses), no recovery phase
“Cynomolgus monkeys (3/sex/group, 5-8 years of age, sexually mature, Mauritius origin) were administered elranatamab at 0, 0.3, 3 and 6 mg/kg SC, Q1W for 14 doses. Scheduled necropsy was performed on Day 93; one day after the last dose. A recovery period was not included.”
Pivotal GLP studies
GLP cynomolgus: 1-month IV (0.01-0.3 mg/kg/wk), 1-month SC (0.3 mg/kg/wk), 3-month SC (0.3, 3, 6 mg/kg/wk); no recovery
“Recovery was not assessed in any of the general toxicology studies.”
DART package
Species: DART
Not conducted (no stand-alone studies); reproductive organs assessed in repeat-dose monkey studies
“Stand-alone reproductive and development toxicity studies have not been conducted with elranatamab. Effects on reproductive organs were assessed as part of the repeat-dose toxicity studies.”
Reproductive & developmental
Not conducted (weight-of-evidence); reproductive organs assessed in 3-month monkey study, no effects
“Embryofetal developmental toxicity was evaluated using a weight of evidence (WOE) risk assessment”
PPND / ePPND: when
No PPND or other DART studies; reproductive organs assessed in monkey studies plus weight-of-evidence assessment
“No reproductive and/or developmental toxicity studies have been conducted with elranatamab. Effects on reproductive organs were assessed in pivotal studies using sexually mature male and female cynomolgus monkeys. Additionally, an integrated weight of evidence assessment was conducted to evaluate the potential for elranatamab to elicit developmental effects.”
Carcinogenicity
Species: carcinogenicity
Not conducted (ICH S9, ICH S6(R1))
“Carcinogenicity studies with elranatamab have not been conducted since they are generally not required for advanced cancer and protein-based biotherapeutics per ICH S9 and ICH S6(R1), respectively.”
Carcinogenicity model
Not conducted (ICH S9, ICH S6(R1))
“Carcinogenicity studies with elranatamab have not been conducted since they are generally not required for advanced cancer and protein-based biotherapeutics per ICH S9 and ICH S6(R1), respectively.”
Carcinogenicity timing
Not required for advanced cancer and protein-based biotherapeutics
“Carcinogenicity studies with elranatamab have not been conducted since they are generally not required for advanced cancer and protein-based biotherapeutics per ICH S9 and ICH S6(R1), respectively.”
Same question, other multispecifics
Rybrevant
amivantamab · EGFR x METUS and ex-US (Australia, Canada, China, France, Japan, Korea, Spain, Taiwan, UK): first-in-human dose escalation/expansion in advanced NSCLC
Talvey
talquetamab · GPRC5D x CD3US and ex-US (Belgium, France, Germany, Israel, Netherlands, Poland, Korea, Spain): first-in-human dose escalation/expansion
Tecvayli
teclistamab · BCMA x CD3US and ex-US (Belgium, Canada, France, Germany, Italy, Netherlands, Spain, Sweden, UK): first-in-human study
Ziihera
zanidatamab · HER2 x HER2 (biparatopic)North America and South Korea: first-in-human study ZWI-ZW25-101 in HER2-expressing cancers
Bizengri
zenocutuzumab · HER2 x HER3Not stated in public reviews
Blincyto
blinatumomab · CD19 x CD3Not stated in public reviews
Columvi
glofitamab · CD20 x CD3Not stated in public reviews
Epkinly
epcoritamab · CD20 x CD3Not stated in public reviews
Hemlibra
emicizumab · FIXa x FXNot stated in public reviews
Imdelltra
tarlatamab · DLL3 x CD3Not stated in public reviews
Kimmtrak
tebentafusp · CD3 x gp100 (TCR fusion)Not stated in public reviews
Korjuny
catumaxomab · EpCAM x CD3Not stated in public reviews
Lynozyfic
linvoseltamab · BCMA x CD3Not stated in public reviews
Ordspono
odronextamab · CD20 x CD3Not stated in public reviews
Removab
catumaxomab · EpCAM x CD3Not stated in public reviews
Vabysmo
faricimab · VEGF-A x Ang-2Not stated in public reviews