Table 2 |.
Inhibitors of TAM receptors under clinical development
| Compound (sponsor) | IC50 in vitro (nM) | Clinical stage | Indications | Adverse effects |
|---|---|---|---|---|
| Crizotinib (Pfizer) | 294 (AXL) | Approved | ALK+ advanced NSCLC, advanced solid or haematological cancers | Abdominal pain, headache, pyrexia |
| Sunitinib (Pfizer) | 5 (AXL) | Approved | Renal cell carcinoma, GIST, pancreatic neuroendocrine tumours | Diarrhoea, fatigue, hypertension |
| Bosutinib (Pfizer) | 560 (AXL) | Approved | Ph+ chronic myeloid leukaemia, solid tumours, Lewy body dementia | Diarrhoea, rash, liver toxicity |
| Gilteritinib (Astellas/Kotobuk) | 0.73 (AXL) | Approved | Relapsed or refractory FLT3-AML | Neutropenia, anaemia, thrombocytopenia |
| Cabozantinib (Exelixis/Ipsen) | 7 (AXL) | Approved | Advanced renal cancer, hepatocellular cancer, thyroid cancer | Fistulas, intra-abdominal, pelvic abscess |
| Batiraxcept (Aravive) | NA | Phase III | Platinum-resistant ovarian cancer, renal and pancreatic cancers | NA |
| Bemcentinib (Bergen Bio) | 14 (AXL) | Phase II | TNBC, NSCLC, pancreatic cancer, brain tumour, mesothelioma, COVID-19 | NA |
| Amuvatinib (Astex) | 10 (AXL) | Phase II (discontinued) | Small cell lung cancer, metastatic solid tumours | Fatigue, alopecia, diarrhoea |
| Foretinib (GSK) | 11 (AXL) | Phase II (discontinued) | TNBC, HER2+ breast cancer, NSCLC | Fatigue, nausea, hypertension |
| ONO-7475 (Ono) | 2.2 (AXL) 0.4 (MERTK) 1.9 (TYRO3) |
Phase I/II | Advanced cancer | NA |
| Sitravatinib (Mirati) | <1 (AXL) <1 (MERTK) <1 (TYRO3) |
Phase I/II | Sarcoma, breast cancer; combination with PD1 inhibitors for solid tumours | NA |
| Dubermatinib (Sumitomo/Tolero) | 27 (AXL) | Phase I | Advanced solid tumours, FLT3-AML | NA |
| S49076 (Servier) | 7 (AXL) 2 (MERTK) |
Phase I | Advanced solid tumours | Peripheral oedema, albumin anaemia |
| SNS314 (Sunesis) | 84 (AXL) | Phase I | Advanced solid tumours | NA |
| BMS-777607 (BMS/Aslan) | 1.1 (AXL) 14 (MERTK) 4.3 (TYRO3) |
Phase I | Advanced or metastatic solid cancer | Anaemia, nausea, constipation |
| RXDX-106 (Ignyta) | 7 (AXL) 29 (MERTK) 19 (TYRO3) |
Phase I (discontinued) | Locally advanced solid tumour | NA |
| Tilvestamab (Bergen Bio) | NA | Phase I | Ovarian cancer | NA |
| Mipasetamab uzoptirine (Bergen Bio/ADC) | NA | Phase I | Advanced solid tumour in combination with gemcitabine | NA |
| Merestinib (Eli Lilly/Dana-Farber) | 2 (AXL) 10 (MERTK) |
Phase I | Biliary tract carcinoma, NSCLC, refractory AML, mantle cell lymphoma, colorectal cancer | Anaemia, thrombocytopenia, leukopenia, neutropenia, nausea, constipation |
| MRX-2843 (Meryx) | 1.3 (AXL) 15 (MERTK) 17 (TYRO3) |
Phase I | Advanced cancer | NA |
ALK+, anaplastic lymphoma kinase-positive; AML, acute myeloid leukaemia; GIST, gastrointestinal stromal tumour; NA, not available; NSCLC, non-small-cell lung cancer; Ph+, Philadelphia chromosome-positive; TNBC, triple-negative breast cancer.