Carotuximab

Overview

Carotuximab (also known as TRC105, DE-122, C‑SN6J) is a chimeric IgG1 monoclonal antibody targeting endoglin (CD105), an endothelial cell protein involved in angiogenesis. It has been tested primarily in oncology (including angiosarcoma, glioblastoma, renal cell carcinoma, hepatocellular carcinoma) and as an intravitreal formulation (DE‑122) for neovascular age-related macular degeneration (nAMD). The most advanced study—a randomized phase 3 trial in angiosarcoma—did not show benefit when carotuximab was added to pazopanib. (precision.fda.gov)

Mechanism of action

• Target: Endoglin (CD105), an endothelial TGF‑β superfamily co-receptor that binds BMP9/BMP10 and modulates ALK1/SMAD1/5/8 signaling essential for vascular development and tumor angiogenesis. (pubmed.ncbi.nlm.nih.gov)
• Drug action: Carotuximab binds endoglin and can block BMP9/10–endoglin signaling, leading to anti‑angiogenic effects; it may also mediate ADCC against endoglin‑expressing endothelial or tumor cells. (aacrjournals.org)

Efficacy (clinical)

• Angiosarcoma (phase 3, TAPPAS): In 123 patients with advanced angiosarcoma, pazopanib plus carotuximab did not improve progression‑free survival versus pazopanib alone (median 4.2 vs 4.3 months; HR 0.98, P=0.95). Objective response rates and overall survival were not improved. (pubmed.ncbi.nlm.nih.gov)
• Glioblastoma (phase 2, bevacizumab‑refractory): Single‑agent carotuximab showed no activity; after protocol amendment, the combination of carotuximab plus bevacizumab produced median overall survival 5.7 months and median PFS 1.8 months in a 16‑patient cohort (open‑label). (pubmed.ncbi.nlm.nih.gov)
• Renal cell carcinoma (phase 1b): Carotuximab plus axitinib was tolerable in 18 heavily pretreated patients; early antitumor activity was reported but without randomized confirmation. (pubmed.ncbi.nlm.nih.gov)
• Hepatocellular carcinoma (phase 1/early 2): Combination with sorafenib showed feasibility and signals of activity in single‑arm studies; carotuximab alone had limited activity. (aacrjournals.org)
• Ophthalmology (nAMD):
• Phase 1 (PAVE): Single intravitreal doses of DE‑122 were generally well tolerated with some anatomic improvements (CST reductions) in small cohorts of refractory nAMD. (pubmed.ncbi.nlm.nih.gov)
• A randomized phase 2a study (AVANTE; DE‑122 + ranibizumab vs ranibizumab) was completed; peer‑reviewed efficacy results have not been published, and development in nAMD has not advanced beyond early-phase data publicly available. (ichgcp.net)

Overall, across tumor types and in nAMD, definitive efficacy has not been demonstrated; the only phase 3 study reported was negative. (pubmed.ncbi.nlm.nih.gov)

Safety

• Systemic (IV): Across early‑phase oncology studies, common adverse events included infusion reactions, headache, anemia (including dose‑limiting hypoproliferative anemia), epistaxis, and telangiectasias—effects consistent with endoglin’s vascular role. In the first‑in‑human study, the MTD was 10 mg/kg weekly (or 15 mg/kg every 2 weeks). In mCRPC phase 1, 20 mg/kg every 2 weeks was tolerated with frequent infusion reactions and anemia. In the TAPPAS phase 3 trial, adding carotuximab increased rates of anemia and epistaxis compared with pazopanib alone. Hypertension/proteinuria typical of VEGF inhibitors were not characteristic of carotuximab. (aacrjournals.org)
• Intravitreal (DE‑122): In a phase 1 nAMD study (single injection), DE‑122 was generally well tolerated; ocular adverse events were mostly mild, and one case of transient posterior eye deposits resolved without sequelae. No serious ocular AEs were reported. (pubmed.ncbi.nlm.nih.gov)

Further reading

• Phase 3 angiosarcoma (TAPPAS): JAMA Oncology 2022. (pubmed.ncbi.nlm.nih.gov)
• First‑in‑human phase 1 in advanced solid tumors: Clinical Cancer Research 2012. (aacrjournals.org)
• Phase 1 in metastatic castration‑resistant prostate cancer: BJU International 2015. (pubmed.ncbi.nlm.nih.gov)
• Phase 1b carotuximab + axitinib in renal cell carcinoma: The Oncologist 2019. (theoncologist.onlinelibrary.wiley.com)
• Carotuximab + sorafenib in HCC (phase 1/early 2): Clinical Cancer Research 2017. (aacrjournals.org)
• Bevacizumab‑refractory glioblastoma (ENDOT) phase 2: Communications Medicine 2023. (pubmed.ncbi.nlm.nih.gov)
• Intravitreal DE‑122 phase 1 in nAMD: Translational Vision Science & Technology 2021. (pubmed.ncbi.nlm.nih.gov)
• Endoglin biology and BMP9/10 binding (mechanistic): JBC 2011; structural analysis of ENG–BMP9 complex (PNAS 2017). (pubmed.ncbi.nlm.nih.gov)
• Official synonyms/identifiers (US FDA UNII/NCATS): (precision.fda.gov)

Notes: Carotuximab remains investigational and is not approved for any indication.

Last updated: Oct 2025