Table 2.
MERTK inhibitors in clinical development
| Name | Target(s) | Malignancies Targeted | Development Phase |
|---|---|---|---|
| MRX-2843 | MERTK, FLT3 | Relapsed/Refractory Advanced and/or Metastatic Solid Tumors (Minson, et al., 2016; D. Yan, et al., 2018) | Phase 1 |
| ONO-7475 | MERTK, AXL | Acute Leukemias (Ruvolo, et al., 2017) | Phase 1 |
| INCB081776 | MERTK, AXL | Advanced Solid tumors (Favata, et al., 2018) | Phase 1 |
| SU-14813 | FLT3, VEGFR, MERTK, AXL, TYRO3, PDGFR, KIT | Advanced Solid Malignancies (Fiedler, et al., 2011) | Phase 1 |
| ASLAN002 | MET, MERTK, AXL, TYRO3, RON, AURKB, FLT3, AXL | Advanced or Metastatic Solid Tumors (Roohullah, et al., 2018) | Phase 1 |
| MGCD265 | MERTK, AXL, TYRO3, MET, VEGFR2 | Non-small cell lung cancer (NSCLC) (Padda, Neal, & Wakelee, 2012; J. Wang, et al., 2018), malignant pleural mesothelioma (MPM) (J. Wang, et al., 2018), triplenegative breast cancer (Linklater, et al., 2016) | Phase 1 |
| Bemcentinib (BGB324) | RET, MERTK, AXL, TYRO3, VEGFR, FLT3, ABL, TIE2 | NSCLC (Felip, et al., 2019), Metastatic or Recurrent Pancreatic Cancer (Beg, et al., 2019), AML/MDS (Sonja Loges, et al., 2019), recurrent GBM (clinicaltrials.gov), Breast Cancer (Yule, et al., 2018), Mesothelioma (Krebs, et al., 2018) | Phase 1, Phase 2 |
| S49076 | MET, FGFR, AXL, MERTK | Advanced solid tumors (Rodon, et al., 2017), Recurrent GBM (Hoang-Xuan, et al., 2016), NSCLC (Viteri, et al., 2018) | Phase 1, Phase 2 |
| Merestinib (LY2801653) | MET, MERTK, AXL, TYRO3, RON, FLT3, MST1R, ROS1, TEK, DDR1/2, MKNK1/2 | Advanced solid tumors including adenocarcinoma of colon/rectum, head and neck SCC, uveal melanoma (Cheng, et al., 2017), cholangiocarcinoma (Barat, et al., 2016), gastric adenocarcinoma. NSCLC (Kawada, et al., 2014; W. Wu, et al., 2013; S. B. Yan, et al., 2018) (Ghanaatgar-Kasbi, Khorrami, Avan, Aledavoud, & Ferns, 2018; He, et al., 2019; S. B. Yan, et al., 2013) | Phase 1, Phase 2 |
| MK2461 | MET, MERTK, RON, VEGFR | Advanced solid tumors (Inoue, et al., 2017; Padda, et al., 2012) | Phase 1, Phase 2 |
| Foretinib (GSK1363089, XL880) | MET, VEGFR2, AXL, MERTK, TYRO3, RON, PDGFRβ, KIT, FLT3, TIE2 | Hepatocellular Carcinoma (Yau, et al., 2017), Recurrent/metastatic Breast Cancer (Simiczyjew, et al., 2018), NSCLC (Leighl, et al., 2017), Advanced/metastatic solid tumor, Squamous Cell Cancer of the Head/Neck (G. Z. Chen, et al., 2017), Papillary Renal Cell Carcinoma (Logan, 2013), Metastatic Gastric Cancer (Shah, et al., 2013) | Phase 1, Phase 2 |
| AT9283 | AURKA, AURKB, JAK, MERTK | Relapsed/refractory Multiple Myeloma (Hay, et al., 2016), Advanced/metastatic solid tumor (Arkenau, et al., 2012; Dent, et al., 2013; Moreno, et al., 2015), Advanced/metastatic non-Hodgkin’s Lymphoma (Qi, et al., 2012), Relapsed/refractory AML/ALL/CML or high risk MDS (Foran, et al., 2014) | Phase 1, Phase 2 |
| Dubermatinib TP-0903 | TYRO3, AXL, MERTK, AURKA, AURKB, JAK2, ALK, ABL1 | Lung cancer (Taverna, et al., 2020), Neuroblastoma (Aveic, et al., 2018), Chronic Lymphocytic Leukemia (Patel, Keating, Wierda, & Gandhi, 2016; Sinha, et al., 2018) | Phase 1, Phase2 |
| Sitravatinib (MGCD516) | VEGFR, PDGFR, KIT, MET, RET, AXL, MERTK, TYRO3 | Squamous Cell Carcinoma, Liposarcoma, Urothelial Carcinoma, Clear Cell Renal Cell Carcinoma, Non-squamous NSCLC, Advanced/Metastatic Kidney Cancer, Advanced/Metastatic Hepatocellular Carcinoma/Gastric Cancer, Advanced Solid Tumors (Dolan, et al., 2019; Du, et al., 2018) | Phase 1, Phase 2, Phase 3 |
| Gilteritinib ASP2215 | TYRO3, AXL, MERTK, | AML (Ha, et al., 2020; Sidaway, 2020; Yun, et al., 2019), Colorectal Cancer (L. Li, Lin, Li, & Li, 2019) | Phase 1, Phase 2, Phase 3, Approved |
| Neratinib | HER2, AXL, MERTK, TYRO3 | Advanced Solid Tumors (Deeks, 2017), Metastatic Breast Cancer (Abraham, et al., 2019; Echavarria, Lopez-Tarruella, Marquez-Rodas, Jerez, & Martin, 2017; Martin, et al., 2017), Recurrent/refractory Pediatric Solid Tumor/Leukemia/Lymphoma, Metastatic Colorectal Cancer (Kavuri, et al., 2015), NSCLC (Bose & Ozer, 2009), Glioblastoma | Phase 1, Phase 2, Phase 3, Approved |
| Lestaurtinib (CEP-701) | FLT3, ACL, MERTK, TYRO3, JAK2, TRKA TRKB, TRKC | Primary Myelofibrosis/Essential Thrombocythemia related Myelofibrosis/Polycythemia Vera related Myelofibrosis (Mascarenhas, et al., 2019), Relapsed/Refractory AML (Knapper, et al., 2017; Levis, et al., 2011), Recurrent/Refractory High-Risk Neuroblastoma (Minturn, et al., 2011; Norris, Minturn, Brodeur, Maris, & Adamson, 2011), ALL (Brown, Levis, McIntyre, Griesemer, & Small, 2006), Advanced Multiple Myeloma, Prostate Cancer (Festuccia, et al., 2007; Kohler, et al., 2012), | Phase 1, Phase 2, Phase 3, Approved |
| Vandetanib (ZD6474) | VEGFR2, VEGFR3, EGFR, AXL, MERTK, TYRO3, RET | Metastatic Medullary Thyroid Cancer (Wells, et al., 2012), Hepatocellular Carcinoma (Hsu, et al., 2012), NSCLC (Morabito, et al., 2010; Yoh, et al., 2017), Gliosarcoma, Glioblastoma (E. Q. Lee, et al., 2015), Breast Cancer (Hatem, et al., 2016), GIST (Glod, et al., 2019), Advanced Pheochromocytoma and Paraganglioma, Advanced Solid Tumors, DIPG (Broniscer, et al., 2013), Papillary Renal Cell Carcinoma (Drevs, et al., 2004), Pancreatic Carcinoma (Kessler, et al., 2016), Ovarian/Fallopian Tube/Peritoneal Cancer, Metastatic Urinary Tract Cancer, Prostate Cancer (A. A. Azad, et al., 2014), Metastatic Colorectal Cancer, High-risk Head/neck Cancer, Biliary Tract Cancer (Kessler, et al., 2016), Esophageal/GE Junction Cancer, Mesothelioma | Phase 1, Phase 2, Phase 3, Approved |
| Sunitinib | PDGF, VEGF, AXL, MERTK, TYRO3, RET, FLT3 | Pancreatic Neuroendocrine Tumors (Blumenthal, et al., 2012), Advanced/Metastatic Renal Cell Carcinoma (Knox, et al., 2017) | Phase 3, Approved |
| Crizotinib (PF2341066) | MET, AXL, MERTK, TYRO3, ALK, RON | Metastatic NSCLC (Landi, et al., 2019; Masuda, et al., 2019), ALCL (Sekimizu, et al., 2018; R. Wang, et al., 2019), Myofibroblastic tumors (Mosse, et al., 2017), Breast Cancer (Ayoub, Al-Shami, Alqudah, & Mhaidat, 2017), Gastric Cancer (Okamoto, et al., 2012), High-Risk Uveal Melanoma (Surriga, et al., 2013), Metastatic/Recurrent Endometrial Cancer, Metastatic Prostate Cancer (Kato, et al., 2018), Lymphoma (Gambacorti Passerini, et al., 2014), Glioblastoma (Junca, et al., 2017; Nehoff, Parayath, McConnell, Taurin, & Greish, 2015), ALK positive tumors, Metastatic Urothelial Cancer, DIPG/HGG (Broniscer, et al., 2013), Recurrent Neuroblastoma (Schulte, et al., 2013; Sekimizu, et al., 2018), Advanced Solid Tumors, Locally advanced/metastatic Kidney Cancer (Schoffski, et al., 2017) | Phase 1, Phase 2, Phase 3, Phase 4, Approved |
| Cabozantinib (XL184, BMS-907351) | AXL, MERTK, TYRO3, VEGFR2, MET, MEK, KIT, RET | Renal cell carcinoma (Bergerot, Lamb, Wang, & Pal, 2019; Lazaro, et al., 2020), Recurrent/metastatic endometrial cancer (Dhani, et al., 2020), Metastatic Prostate Cancer (Corn, et al., 2020), Adrenocortical carcinoma (Kroiss, et al., 2020), Thryoid Cancer (Ancker, Kruger, Wehland, Infanger, & Grimm, 2019), Advanced Hepatocellular Carcinoma (Abou-Alfa, et al., 2018; Personeni, Rimassa, Pressiani, Smiroldo, & Santoro, 2019), Urothelial Carcinoma (Bergerot, et al., 2019), Esophageal Squamous Cell Carcinoma (P. W. Yang, et al., 2019) | Phase 1, Phase 2, Phase 3, Phase 4, Approved |
| Bosutinib (SKI-606, PF-5208763) | SRC, ABL, AXL, MERTK, TYRO3 | Ph+ CML (Assi, et al., 2017; Shen, Wilson, Gleason, & Khoury, 2014), Metastatic Solid Tumors – non-squamous non-small cell lung cancer/pleural malignant mesothelioma/bladder cancer/urethral cancer/ovarian cancer/peritoneal cancer/thymic cancer/uterine cervical cancer, Glioblastoma (Taylor, et al., 2015), CML (Cortes, et al., 2018; Doan, Wang, & Prescott, 2015), Ph+ ALL with CD22 expression, Pancreatic Cancer (Daud, et al., 2012), Breast Cancer (Campone, et al., 2012; Vultur, et al., 2008), Colorectal Cancer (Daud, et al., 2012), Cholangiocarcinoma, Advanced/Recurrent Solid Tumors (Isakoff, et al., 2014) | Phase 1, Phase 2, Phase 3, Phase 4, Approved |