What is the efficacy of trebananib in colon cancer?
In the efficacy analysis, trebananib showed evidence of antitumor activity. Two patients, one with colon cancer and the other with bladder cancer, achieved a partial response. Both of them had a durable partial response and were on treatment at the time of data cutoff.
How much trebananib is safe to take?
Results of our study show that weekly infusions of trebananib up to 30 mg/kg were tolerated without any treatment discontinuation because of adverse events. Adverse events were mild to moderate in most patients. No DLTs were observed. These results are consistent with those of the phase 1 single-agent study conducted in the United States [16].
Is trebananib safe in Japanese patients with advanced solid tumors?
Trebananib was tolerated and showed acceptable safety profile in Japanese patients with advanced solid tumors. The pharmacokinetic profiles were similar to those in the previous studies in the United States. Trebananib also showed evidence of durable antitumor activity in some patients.
How does trebananib affect serum concentration and area under the curve?
Exposure to trebananib (maximum observed concentration [Cmax] and area under the serum concentration–time curve from time 0 to 168 h post-dose [AUC0-168]) on both weeks 1 and 4 appeared to increase according to the dose administered.
What is Trebananib used for?
Trebananib (formerly AMG 386) is a peptibody—an engineered protein with properties of both peptides and antibodies—which inhibits the binding of angiopoietin 1/2 to the Tie2 receptor thereby inhibiting the angiopoietin axis. Angiopoietins are associated with non VEGF angiogenesis. Ang1 impacts vessel quality while Ang2 influences vessel quantity. The angiopoietins are also involved in lymphangiogenesis, the formation of new lymphatic vessels, which plays a key role in tumor metastasis (Holash et al., 1999 ). Trebananib is an anti-angiogenesis peptibody that inhibits the binding of angiopoietin 1/2 to the Tie2 tyrosine-protein kinase receptor, thus interfering with the additional blood supply that supports oncogenesis.
What is Trebananib? What are its functions?
Trebananib is a peptide-Fc fusion protein that targets the Ang1/Ang2/Tie2 pathway and inhibits angiogenesis by blocking the interaction between Ang1/Ang2 with the Tie2 receptor. A phase III trial of weekly paclitaxel with AMG 386 or placebo for patients with recurrent EOC, FTC, and PPC revealed marginal improved PFS (7.2 vs 5.4 months, HR =0.66; P < 0.0001), but no difference in OS [68]. Continued studies are ongoing to further evaluate the activity of AMG 386 in women with recurrent and newly diagnosed ovarian cancer (TRINOVA-3 20101129/ENGOT-ov2, NCT01493505) and endometrial cancer ( Table 5.2 ).
Is Trebananib an anti-Ang-1 antibody?
Several anti-Ang-1 antibodies have been developed, which have shown some clinical capacity. Li XY et al. (2016) have reviewed the outcome of some clinical trials using the Ang-1 inhibitor trebananib, a recombinant peptide-Fc fusion protein, which binds to the angiopoietins and interferes with their interaction with Tie-2. These trials showed clear improvements in PFS and overall survival of patients with ovarian cancer. The benefits seemed to be superior to those observed with inhibitors of VEGF or VEGFR. However, on the negative side are the significant side effects associated with all three modes of treatment. Much work has been carried out with trebananib on other forms of cancer. Atkins et al. (2015) found some benefit from the administration of a combination of trebananib with the VEGFR inhibitor sunitinib to patients with metastatic clear cell renal cell carcinoma. The clinical outcome in patients with recurrent endometrial cancer on trebananib as a single agent was uninspiring ( Moore et al., 2015 ). Neither have other angiopoietin inhibitors shown any clinical benefit deemed worthy of discussion.
What is Trebananib? What are its functions?
Trebananib is a peptide-Fc fusion protein that targets the Ang1/Ang2/Tie2 pathway and inhibits angiogenesis by blocking the interaction between Ang1/Ang2 with the Tie2 receptor. A phase III trial of weekly paclitaxel with AMG 386 or placebo for patients with recurrent EOC, FTC, and PPC revealed marginal improved PFS (7.2 vs 5.4 months, HR =0.66; P < 0.0001), but no difference in OS [68]. Continued studies are ongoing to further evaluate the activity of AMG 386 in women with recurrent and newly diagnosed ovarian cancer (TRINOVA-3 20101129/ENGOT-ov2, NCT01493505) and endometrial cancer ( Table 5.2 ).
What are the main targets of antiangiogenic therapy?
Angiogenesis is a complex process regulated by multiple signaling pathways. At present, the main target of antiangiogenic therapy is VEGF and its receptor . However, it is impossible for angiogenesis inhibitors to suppress all angiogenic factors and their downstream signaling pathways. When the VEGF signaling pathway is blocked, compensation may occur via an increase in other growth factors in the microenvironment. Fibroblast growth factor (FGF), plated-derived growth factor (PDGF), stromal cell derived factor1 alpha (SDF-1α), angiopoietin (Ang), and tumor necrosis factor-α (TNF-α) are all angiogenesis-promoting factors. They initiate signal transduction after binding to their specific receptors, causing proliferation and migration of endothelial cells and inducing the formation of new blood vessels. An increase in angiogenic factors in advanced renal cell carcinoma occurs before the progression of antiangiogenic therapy [ 10 ]. After the effective inhibition of VEGFR2 in the short-term treatment of pancreatic tumors, recurrence is caused by upregulated expression of fibroblast growth factor (FGF)-1, FGF-2, angiopoietin (Ang)-1, and other proteins. Therefore, blocking FGF-related proteins in conjunction with chemotherapy may reduce the tumor recurrence rate [ 11 ]. In some models, short-term inhibition of VEGF-VEFGR accelerates tumor invasion and metastasis, and tumor cells induce neovascularization to avoid antiangiogenic therapy [ 12, 13 ].
Is Trebananib an anti-Ang-1 antibody?
Several anti-Ang-1 antibodies have been developed, which have shown some clinical capacity. Li XY et al. (2016) have reviewed the outcome of some clinical trials using the Ang-1 inhibitor trebananib, a recombinant peptide-Fc fusion protein, which binds to the angiopoietins and interferes with their interaction with Tie-2. These trials showed clear improvements in PFS and overall survival of patients with ovarian cancer. The benefits seemed to be superior to those observed with inhibitors of VEGF or VEGFR. However, on the negative side are the significant side effects associated with all three modes of treatment. Much work has been carried out with trebananib on other forms of cancer. Atkins et al. (2015) found some benefit from the administration of a combination of trebananib with the VEGFR inhibitor sunitinib to patients with metastatic clear cell renal cell carcinoma. The clinical outcome in patients with recurrent endometrial cancer on trebananib as a single agent was uninspiring ( Moore et al., 2015 ). Neither have other angiopoietin inhibitors shown any clinical benefit deemed worthy of discussion.