Table 1.
Mechanisms of action of different MET antibodies.
| Antibody | Structure | Epitope on MET |
HGF Displacement |
MET Downregulation |
MET Shedding |
Antibody-Dependent Immune Functions | Antibody Drug Conjugated |
Clinical Trial * |
|---|---|---|---|---|---|---|---|---|
| Onartuzumab (OA-5D5, MetMab) |
Monovalent IgG1/k | SEMA (blades 4/5/6) |
Yes | No | No | No | No | Ph III |
| Telisotuzumab (ABT-700) |
Bivalent IgG1/k |
IPT-1 | Yes + inhibition of receptor dimerization |
Yes | Not reported |
No | Teliso-V (ABBV-399) conjugated with Vedotin |
Ph III (Telisotuzumab) Ph III (Teliso-V) |
| Emibetuzumab (LY 2875358) |
Bivalent IgG4/k |
SEMA (blades 2/3) |
Yes | Yes | No | No | No | Ph II |
| Amivantamab (JNJ-61186372) |
Bispecific (MET/EGFR) IgG1/k |
SEMA (blade2) |
Yes | Yes | Not reported |
ADCC ADCP ADCT |
No | Ph III |
| ARGX-111 | Bivalent IgG1/k |
SEMA (blades 2/3) |
Yes | Yes | No | ADCC | No | Ph I |
| Sym015 (1:1 mix of Hu9006 and Hu9338) |
Bivalent mAbs, IgG1/k |
SEMA (blade 2, blade 3) |
Yes | Yes | Not reported |
ADCC CDC |
No | Ph i/II |
| SAIT-301 | Bivalent IgG2/k | SEMA (MET α-chain) |
Yes | Yes | No | No | Ph I | |
| REGN-5093 (METxMET) |
Biparatopic IgG1,IgG3/k |
SEMA (blade 3, blades 5/6) |
Yes | Yes + inhibition of surface receptor recycling |
Not reported |
No | REGN-5093-M114 (METxMET-M114) conjugated with a maytansin derivative |
Ph I/II (REGN-5093) Ph I/II (REGN-5093-M114) |
| hOA-DN30 | Monovalent IgG1/k |
IPT-4 | No | No | Yes | No | No | IND completed; clinical trial expected in 2024 # |
* for each antibody, the most advanced clinical phase is reported, as described in May 2024 in www.clinicaltrials.gov (accessed on 15 May 2024). # the clinical trial will test a version of hOA-DN30 with some amino acid changes. ADCC: Antibody-Dependent Cellular Cytotoxicity; ADCP: Antibody-Dependent Cellular Phagocytosis; ADCT: Antibody-Dependent Cellular Trogocytosis; and CDC: Complement-Dependent Cytotoxicity.