Clinical phase I/II study with the insulin-like growth factor-1 receptor inhibitor AXL1717: Future implications for patients with squamous non-small cell lung carcinoma?

Abstract

e13019 Background: Inhibition of the insulin-like growth factor-1 receptor (IGF-1R) has resulted in extensive antitumor effects. AXL1717 is a small-molecule inhibitor of the IGF-1R without inhibition of closely related receptors including the insulin receptor and has shown extensive effects against a wide range of tumors in animals. Preclinical testing in two animal species showed excellent tolerability together with good oral bioavailability. Methods: AXL1717 is presently tested as an orally administrated single-agent treatment in an open-label phase I/II clinical study in advanced cancer patients with solid tumors that progress in spite of several lines of treatment. The first part (phase IA) consisted of single-day BID dosing every three weeks with consecutive dose escalations. The second part (phase IB) consists of 7 days or longer BID dosing every three weeks, dosing range being 520-700 mg BID. Nonprogressing patients could continue treatment within a compassionate use setting. Study objectives included identifying recommended phase II dose, pharmacokinetics, safety, and biological effects. The study followed GCP, was approved by Medical Product Agency and regional ERB. Results: The phase IA part of the study has successfully been concluded after 154 treatments given to 16 patients. The results show that AXL1717 can be administered as a single-day BID treatment in very high doses with excellent tolerability and good bioavailability. Dose-limiting toxicity has not been reported. Preliminary results from phase IB after 13 patients showed that AXL1717 can be given in multidose setting with good tolerability. Neutropenia was seen as dose-limiting toxicity at high exposure of the agent. Even though the study was not designed to show efficacy, 4/6 patients with squamous non-small cell lung cancer showed signs of tumor response including tumor necrosis on PET and prolonged stationary disease. Conclusions: This first clinical study of AXL1717 has shown that the agent can be administrated safely orally to advanced stage cancer patients resulting in good bioavailability and tolerability. Encouraging signs of tumor response were seen. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Axelar AB Axelar AB