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
Blincyto: what was done before first-in-human, and what came after?
blinatumomab · CD19 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 Blincyto 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 assigned; lymphoid tissues target organs (lymphocyte depletion, decreased cellularity); chimp hypotension dose-limiting at 0.12 ug/kg (FDA pharmacology/toxicology review, p. 12)
Longest repeat-dose systemic studies
Longest repeat-dose study and recovery
13-week SC mouse study with murine surrogate muS103new, 4-week recovery
“Therefore, in the 13-week repeat-dose toxicology study in mice, BALB/c mice were administered muS103new (0, 1, or 5 mg/kg/day; 0, 2, or 10 mg/kg/day) by subcutaneous injection twice daily with an 8-hour interval between doses for 13 weeks with a 4-week recovery period.”
Pivotal GLP studies
4-week IV and 13-week SC mouse studies (surrogate muS103new); 5-weekly-dose IV infusion chimpanzee study (blinatumomab)
“For this review, the 4-week (summarized) and 13-week studies of muS103new in mice and the 5-weekly dose study of blinatumomab in chimpanzees were reviewed.”
DART package
Species: DART
Mouse EFD with murine surrogate only; no fertility studies
“In an embryo-foetal developmental toxicity study performed in mice, the murine surrogate crossed the placenta to a limited extent (foetal-to-maternal serum concentration ratio < 1%) and did not induce embryo-foetal toxicity or teratogenicity.”
Reproductive & developmental
Mouse EFD with surrogate: placental transfer, no embryo-fetal toxicity or teratogenicity; no fertility studies
“Studies in mice using the surrogate showed no drug-related effects in male or female reproductive organs and did not reveal any embryo-fetal toxicity or teratogenicity.”
PPND / ePPND: when
No PPND study; reproductive toxicity limited to mouse EFD with murine surrogate (no reason given)
“Reproductive toxicity studies have not been conducted with blinatumomab. In an embryo-foetal developmental toxicity study performed in mice, the murine surrogate crossed the placenta to a limited extent”
Carcinogenicity
Species: carcinogenicity
Not conducted (advanced cancer indication, ICH S9)
“As it is being developed for advanced cancer indications, no carcinogenicity studies have been conducted, in accordance with ICH S9.”
Carcinogenicity model
Not conducted (advanced cancer indication, ICH S9)
“As it is being developed for advanced cancer indications, no carcinogenicity studies have been conducted, in accordance with ICH S9.”
Carcinogenicity timing
Not required for advanced cancer indication (ICH S9)
“As it is being developed for advanced cancer indications, no carcinogenicity studies have been conducted, in accordance with ICH S9.”
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
Columvi
glofitamab · CD20 x CD3Not stated in public reviews
Elrexfio
elranatamab · BCMA 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