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
Lunsumio: what was done before first-in-human, and what came after?
mosunetuzumab · CD20 x CD3
Before first-in-human
First-in-human: where
US, Republic of Korea, Canada: dose-escalation part (Group A) of study GO29781 in patients with R/R B-cell NHL
“● Group A (n=33): United States 25 (5), Republic of Korea 7 (2), Canada 1 (1).”
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
MABEL-type: EC20 from in vitro human PBMC cytokine release / T-cell activation assay
“The results (EC20 values) were used to inform the starting dose in the first in human study.”
Longest repeat-dose systemic studies
Longest repeat-dose study and recovery
26-week GLP cynomolgus monkey study (IV step-up then weekly); recovery phase not stated
“In the pivotal 26-week GLP toxicity study (16-1815), exposure was maintained in 7/7 animals in the 0.5 mg/kg target-dose group, and in 4/7 surviving animals past TK Day 84 in the 0.1 mg/kg group.”
Pivotal GLP studies
GLP single-dose IV/SC monkey (7-week observation); 4-week step-up DRF; GLP 26-week weekly IV step-up monkey study (16-1815)
“A step-up mosunetuzumab dosing regimen was used in the 4-week DRF study and the pivotal GLP 26-week repeat-dose toxicity studies (Study 16-2088 and 16-1815) by splitting the first 1 mg/kg dose to Day 1 (0.2 mg/kg) and Day 2 (0.8 mg/kg)”
DART package
Species: DART
Not conducted; NHP EFD and pre/postnatal study waived on weight of evidence (FDA agreed)
“A briefing book, including the WOE-based risk assessment and a request to waive a non-human primate embryo-fetal and prenatal/postnatal development study, was submitted to the FDA (dated 3 April 2018; Reference ID: 4277993). In a written communication from the FDA dated 14 June 2018, the Agency agreed to the waiver request.”
Reproductive & developmental
Not conducted (dedicated DART); NHP EFD/PPND waived on weight of evidence; no reproductive organ effects in 26-week monkey study
“A briefing book, including the WOE-based risk assessment and a request to waive a non-human primate embryo-fetal and prenatal/postnatal development study, was submitted to the FDA (dated 3 April 2018; Reference ID: 4277993).”
PPND / ePPND: when
Monkey EFD/prenatal-postnatal study waived by FDA on weight of evidence
“A briefing book, including the WOE-based risk assessment and a request to waive a non-human primate embryo-fetal and prenatal/postnatal development study, was submitted to the FDA (dated 3 April 2018; Reference ID: 4277993). In a written communication from the FDA dated 14 June 2018, the Agency agreed to the waiver request.”
Carcinogenicity
Species: carcinogenicity
Not conducted (oncology indication, ICH S6(R1))
“No carcinogenicity studies have been conducted with mosunetuzumab and are not planned for the intended oncology indication, as per Guidance for Industry S6R1.”
Carcinogenicity model
Not conducted (oncology indication, ICH S6(R1))
“No carcinogenicity studies have been conducted with mosunetuzumab and are not planned for the intended oncology indication, as per Guidance for Industry S6R1.”
Carcinogenicity timing
Not required; none conducted or planned for the oncology indication
“No carcinogenicity studies have been conducted with mosunetuzumab and are not planned for the intended oncology indication, as per Guidance for Industry S6R1.”
Same question, other multispecifics
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
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