Table 1 HER2-based immunotherapy in clinic
From: Recombinant immunotoxins development for HER2-based targeted cancer therapies
Therapeutics | Features | Status | Tumor type | Refs. |
|---|---|---|---|---|
Antibody | ||||
 Trastuzumab | ECD IV of HER2 binding humanized monoclonal antibody | FDA approved | HER2-positive breast cancer | [34] |
 Pertuzumab | ECD II of HER2 binding humanized monoclonal antibody | FDA approved | HER2-positive breast cancer | [38] |
 Margetuximab | Increased binding to activating Fcγ receptor IIIA (CD16A) and decreased binding to inhibitory Fcγ receptor IIB (CD32B) | FDA approved | HER2-positive BC, gastric cancers and gastro-esophageal junction cancer | [41] |
 BTRC4017A | T-cell dependent (CD3) bispecific antibody | Phase I (NCT03448042) | HER2-positive solid tumors | [42] |
 PRS-343 | T-cell dependent (CD137) bispecific antibody | Phase I (NCT03330561, NCT03650348) | HER2-positive solid tumors | [43] |
 GBR-1302 | T-cell dependent (CD3) bispecific antibody | Phase I (NCT02829372) | Breast cancer | [44] |
 ZW25 | Bispecific antibody against two distinct HER2 epitopes | Phase I (NCT02892123) Phase II (NCT04513665) | Breast cancer, endometrial cancer, carcinosarcoma | [45] |
Antibody–drug conjugate | ||||
 Trastuzumab– emtansine | Trastuzumab antibody linked to anti-mitotic agent, mertansine | FDA approved | HER2-positive metastatic breast cancer | [46] |
 ARX788 | HER2 targeting mAb linked to the AS269 (a highly potent tubulin inhibitor) | Phase I (NCT02512237) | HER2-positive metastatic breast cancer | [47] |
 DS8201a | Trastuzumab–deruxtecan (DNA topoisomerase I inhibitor) | Phase I (NCT04042701) | Advanced/metastatic NSCLC | [48] |
 MEDI4276 | Bispecific antibody targeting two different HER2 epitopes, conjugated with MMETA (a potent tubulysin-based microtubule inhibitor) | Phase I/II (NCT02576548) | HER2 positive breast cancer | [49] |
 MM302 | Pegylated liposomal doxorubicin formulation, with anti-HER2 antibody fragments coupled to its surface. | Phase I (NCT01304797) | HER2-positive breast cancer | [50] |
 PF-06804103 | Anti-HER2 monoclonal antibody conjugated with the cytotoxic agent Aur0101 | Phase I (NCT03284723) | HER2 positive breast cancer and gastric cancer | [51] |
 SYD985 | Trastuzumab–duocarmazine | Phase I (NCT02277717) Phase II (NCT04205630) Phase III (NCT03262935) | Metastatic breast cancer | [52] |
 XMT-1522 | Anti HER2 IgG1 conjugated with the tubulin inhibitor AF-HPA | Phase I (NCT02952729) | Advanced breast cancer, gastric cancer and NSCLC | [53] |
Tyrosine kinase inhibitor | ||||
 Lapatinib | HER1 and HER2 tyrosine kinases inhibitor | FDA approved | Metastatic breast cancer | [54] |
 Neratinib | HER1, HER2, and HER4 tyrosine kinases inhibitor | FDA approved | Early-stage HER2-positive breast cancer | [55] |
 Afatinib | ErbB family tyrosine kinases inhibitor | FDA approved | Metastatic NSCLC | [56] |
 Ibrutinib | ErbB family tyrosine kinases inhibitor | FDA approved | CLL, MCL, DLBCL, MM, FL and WM | [57] |
 Pyrotinib | HER1, HER2, and HER4 tyrosine kinases inhibitor | Phase I (NCT01937689) | Breast cancer | [58] |