Table 1.
Selected monoclonal antibodies and tyrosine kinase inhibitors against co-stimulatory and checkpoint molecules and growth factors that are in clinical phase I–III trials either alone or in combination with RT, CT or immunotherapy.
| Target | Drug | Developer | Target disease (not all listed) |
|---|---|---|---|
| Co-stimulatory molecules | |||
| CD40 | CP-870,893 Dacetuzumab Lucatumumab |
Pfizer Seattle Genetics, Inc. Novartis |
Melanoma; pancreatic carcinoma; renal-cell carcinoma; breast cancer Diffuse large B-cell lymphoma (DLBCL); chronic lymphocytic leukemia (CLL); non-hodgkin’s lymphoma (NHL); multiple myeloma (MM) CLL; NHL; MM |
| CD134 (OX40) | MEDI6469 | AstraZeneca | Advanced solid tumors; aggressive B-cell lymphomas; HNC; metastatic prostate cancer |
| CD137 | BM-663513 | Bristol-Myers Squibb (BMS) | Melanoma; advanced solid malignancies; B-cell malignancies |
| Checkpoint inhibitors | |||
| CTLA-4 | Tremelimumab Ipilimumab |
Pfizer BMS |
Metastatic melanoma; HNSCC; NSCLC; advanced solid malignancies Yervoy™ approved for unresectable or metastatic melanomaa; lymphoma; NSCLC; HNC; prostate, pancreatic, liver, lung, kidney and renal-cell cancer; melanoma |
| PD-1 | Nivolumab Pembrolizumab Pidilizumab |
BMS Merck CureTech Ltd |
Obvido® approved for unresectable or metastatic melanoma and NSCLCa; MM; NHL Renal-cell carcinoma (RCC); advanced solid tumors; melanoma; NSCLC Keytruda® approved for advanced or unresectable melanomaa; NSCLC; HNSCC; lymphoma; breast cancer; malignant glioma; melanoma MM; gliomas; lymphomas |
| PD-L1 | BMS-936559 MEDI4736 |
BMS AstraZeneca |
Recurrent solid tumors Advanced solid tumors; NSCLC; HNSCC; GBM |
| Growth factor inhibitors | |||
| EGFR | Cetuximab Panitumumab Gefitinib Erlotinib |
BMS Amgen AstraZeneca Genentech/Roche |
Erbitux® approved for K-ras wild-type, EGFR-expressing metastatic colorectal cancer and recurrent/metastatic HNSCCa; NSCLC; HNSCC; colorectal cancer Vectibix™ approved for colorectal cancera; HNSCC; colorectal cancer Iressa® approved for NSCLCa; HNC; skin, breast, colorectal cancer; GBM; NSCLC Tarceva® approved for NSCLC and pancreatic cancera; HNC; prostate, breast, esophageal, colorectal cancer; NSCLC; pancreatic cancer |
| HER2/neu receptor | Trastuzumab | Genentech/Roche | Herceptin® approved for HER2-overexpressing breast cancer and HER2-overexpressing metastatic gastric or gastroesophageal (GE) junction adenocarcinomaa; breast cancer; NSCLC |
| VEGFRs, PDGFRs, FLT-3, c-Kit, RET; CSF-1R | Sunitinib | Pfizer | Sutent® approved for pancreatic neuroendocrine tumors (pNET); kidney cancer and gastrointestinal stromal tumor (GIST)a; pNET; kidney cancer; GIST; RCC, pancreatic and bladder cancer |
| VEGFRs, PDGFRs, RAF, FLT-3, c-Kit, RET | Sorafenib | Bayer | Nexavar® approved for recurrent or metastatic, progressive differentiated thyroid carcinoma (DTC), unresectable hepatocellular carcinoma (HCC) and advanced RCCa; HCC; RCC, bladder cancer; brain neoplasms; advanced solid tumors |
| VEGFRs | Axitinib | Pfizer | Inlyta® approved for advanced RCCa; advanced gastric cancer; hepatocellular and colorectal carcinoma; prostate cancer; GBM; RCC; NSCLC |
| VEGFRs, PDGFRs, c-Kit | Pazopanib | GlaxoSmithKline | Votrient® approved for advanced soft tissue sarcoma and RCCa; ovarian cancer; fallopian tube cancer; peritoneal carcinoma; NSCLC; RCC |
| VEGF-A | Bevacizumab | Genentech/Roche | Avastin® approved for recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, recurrent/metastatic cervical cancer, metastatic HER2 negative breast cancer, RCC, GBM, NSCLCa; advanced cancers |
aFDA-approved drugs.