AMC303 inhibited tumor growth and prevented the spread of colorectal, and other cancer cells, and of a pancreatic cancer in a mouse model, amcure reported at the American Association for Cancer Research’s annual meeting in Washington.
The company is developing the therapy for colon cancer and a number of other solid tumors besides pancreatic cancer.
In addition to the results of the three-week experimental study, the poster session that amcure presented at the conference covered AMC303’s mechanism of action. The session was titled “Allosteric inhibition of the Receptor Tyrosine Kinases c-MET, RON and VEGFR-2 via the co-receptor CD44v6 by the novel compound AMC303.”
Cancer cells that have stem-cell-like characteristics, and are at high risk of spreading, express the cell surface receptor CD44. For example, colorectal cancer stem cells express the CD44v6 version of the receptor, which sends signals that cause the cells to migrate and generate tumors at new locations.
AMC303 inhibits CD44v6 and three other receptor tyrosine kinases: c-MET, RON and VEGFR-2. Receptor tyrosine kinases, or RTKs, are cell surface receptors that activate signaling pathways within cells. This means RTKs are key regulators of critical cell processes, including proliferation and differentiation, cell survival and metabolism, cell migration, and cell cycle control.
Amcure is in the midst of evaluating AMC303 in a multicenter, open-label, dose-escalation Phase 1/1b clinical trial (NCT03009214). The study covers patients with advanced metastatic solid tumors of the pancreas, colon, lungs, digestive system, head and neck.
The first part of the two-part study is aimed at finding the maximum tolerable dose of AMC303 for solid-tumor patients. It will assess the safety, tolerability, and side effects of five ascending doses administered intravenously.
Researchers have chosen doses of 0.1 mg/kg, 0.5 mg/kg, 1.5 mg/kg, 4 mg/kg and 10 mg/kg. The dose that they deem optimum will be further tested in the second part of the Phase 1 trial.
The trial will also look at the pharmacokinetics and pharmacodynamics of AMC303 — that is, how it behaves in the body.
“So far the data generated with AMC303 indicate that it combines a strong anti-tumor and anti-metastatic effect,” Klaus Dembowsky, CEO of amcure, said in a press release. “These encouraging results solidify our belief in AMC303’s potential as a novel solid tumor treatment option and bode well for the ongoing Phase I study results.”