Table 3.
HGF/MET-Targeted Agents in Clinical Development
| Compound | Targets | Study Phase | Treatment Combinations and Disease Sites of Ongoing Studies | Reference |
|---|---|---|---|---|
| Crizotinib (PF-02341066) | MET, ALK TKI | Phase I/III | NSCLC with ALK translocation or inversion; ALK-positive NSCLC; crizotinib v pemetrexed and cisplatin; anaplastic large cell lymphoma; erlotinib for NSCLC; PF-00299804 for NSCLC; pharmacokinetic and bioavailability studies in advanced solid tumors | 11,12 |
| Cabozantinib (XL184) | MET, RET, VEGFR2 TKI | Phase I/III | Advanced solid tumors; temozolomide and radiation for malignant glioma; erlotinib for NSCLC; rosiglitazone for RCC, thyroid cancer; medullary thyroid cancer, lymphoma, malignant glioma | 13 |
| Foretinib (XL880) | MET, VEGFR2 TKI | Phase II | Erlotinib for NSCLC; lapatinib/breast cancer; papillary RCC, HCC, breast cancer | 14 |
| MetMAb (PRO143966) | Anti-MET Ab | Phase II | Paclitaxel, bevacizumab for breast cancer; erlotinib for NSCLC | 15 |
| Rilotumumab (AMG 102) | HGF Ab | Phase II | Platinum chemotherapy for SCLC; panitumumab for wild-type KRAS mCRC; erlotinib for advanced NSCLC; mitoxantrone and prednisone for CRPC; bevacizumab for malignant glioma; epirubicin, cisplatin, and capecitabine for gastric or esophagogastric junction cancer; pemetrexed and cisplatin/mesothelioma for RCC, ovarian cancer | 16–19 |
| AMG 208 | MET TKI | Phase I | Advanced solid tumors | 20 |
| ARQ 197 | MET TKI | Phase II | Irinotecan and cetuximab for mCRC; gemcitabine for advanced solid tumors; sorafenib for advanced solid tumors; erlotinib for NSCLC; RCC, alveolar soft tissue sarcoma, clear cell sarcoma, gastric cancer, HCC, GCT | 21 |
| AV-299 | HGF Ab | Phase I/II | Advanced solid tumors, lymphomas, myeloma; gefitinib for NSCLC | 20 |
| E7050 | Phase I/II | Sorafenib for HCC; advanced solid tumors | 20 | |
| MGCD265 | MET, VEGFR1-3, Ron, Tie2 TKI | Phase I/II | Erlotinib or docetaxel for advanced solid tumors or NSCLC; advanced solid tumors | 22 |
Abbreviations: ALK, anaplastic lymphoma kinase; CRPC, castration-resistant prostate cancer; GCT, germ cell tumor; HCC, hepatocellular carcinoma; HGF, hepatocyte growth factor; HGF Ab, neutralizing antibody against human HGF; mCRC, metastatic colorectal carcinoma; NSCLC, non–small-cell lung cancer; RCC, renal cell carcinoma; SCLC, small-cell lung cancer; SD, standard deviation; TKI, tyrosine kinase inhibitor; VEGFR, vascular endothelial growth factor receptor.