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
Tecvayli: what was done before first-in-human, and what came after?
teclistamab · BCMA x CD3
Before first-in-human
First-in-human: where
US and ex-US (Belgium, Canada, France, Germany, Italy, Netherlands, Spain, Sweden, UK): first-in-human study
“Trial Location: This study was conducted at 39 centers that treated at least 1 subject in Belgium (2), Canada (4), France (6), Germany (3), Italy (2), Netherlands (1), Spain (7), Sweden (3), the United Kingdom (3), and the United States (8).”
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 Tecvayli 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: NOEL 30 mg/kg/week (highest dose); no PD activity or adverse effects in monkey (FDA multi-discipline review, p. 44)
Longest repeat-dose systemic studies
Longest repeat-dose study and recovery
5-week weekly IV cynomolgus monkey study with 8-week recovery
“Monkeys were administered teclistamab (0 [control], 1, 10, or 30 mg/kg/dose, IV) once weekly for five total doses followed by an 8-week recovery period.”
Pivotal GLP studies
GLP 5-week weekly IV monkey study (1, 10, 30 mg/kg) with 8-week recovery; 3-month study waived; rabbit SC local tolerance
“Monkeys were administered teclistamab (0 [control], 1, 10, or 30 mg/kg/dose, IV) once weekly for five total doses followed by an 8-week recovery period.”
DART package
Species: DART
Not conducted; weight-of-evidence assessment (no informative species)
“No reproductive and developmental toxicity studies were conducted for teclistamab.”
Reproductive & developmental
Not conducted; weight-of-evidence assessment (BCMA biology, knockout mice); no reproductive tissue findings in 5-week study
“No reproductive and developmental toxicity studies were conducted for teclistamab.”
PPND / ePPND: when
Not conducted: reproductive and developmental toxicity studies would not be meaningful and are not warranted
“Similarly, reproductive and developmental toxicity studies would not provide meaningful information and are not warranted to support a BLA.”
Carcinogenicity
Species: carcinogenicity
Not conducted (ICH S9, advanced cancer)
“Carcinogenicity studies were not conducted with teclistamab.”
Carcinogenicity model
Not conducted (ICH S9, advanced cancer)
“Carcinogenicity studies were not conducted with teclistamab. As indicated in the ICH S9 guidance, carcinogenicity studies are not warranted to support marketing for therapeutics intended to treat patients with advanced cancer.”
Carcinogenicity timing
Not required; FDA agreed carcinogenicity studies not needed
“We agree that carcinogenicity studies are not needed to support the approval of BLA 761261.”
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
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