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A novel oral insulin-like growth factor-1 receptor pathway modulator and its implications for patients with non-small

Simon Ekman1, Johan Harmenberg2, Jan-Erik Frödin3

  • 1a Department of Immunology , Genetics and Pathology, Uppsala University , Uppsala , Sweden.

Acta Oncologica (Stockholm, Sweden)
|July 11, 2015
PubMed
Abstract

Insights

AXL1717, an oral insulin-like growth factor-1-receptor pathway modulator, showed a good safety profile and promising efficacy in advanced solid tumors, particularly non-small cell lung cancer (NSCLC). The recommended phase II dose (RP2D) was determined to be 390 mg BID for four weeks.

Area of Science:

  • Oncology
  • Pharmacology
  • Clinical Trials

Background:

  • Investigated AXL1717, an oral small molecule targeting the insulin-like growth factor-1-receptor (IGF-1R) pathway.
  • Focused on patients with advanced solid tumors.

Purpose of the Study:

  • Characterize safety, efficacy, and pharmacokinetics of AXL1717.
  • Determine the recommended phase II dose (RP2D) and maximum tolerated dose (MTD).

Main Methods:

  • Phase Ia/b, prospective, single-armed, open-label, dose-escalation study.
  • Dose-finding for single (Ia) and multi-day (Ib) dosing.
  • Safety, efficacy, and pharmacokinetic assessments.

Main Results:

  • AXL1717 was well-tolerated up to 2900 mg BID; neutropenia was the only dose-limiting toxicity.
  • RP2D established at 390 mg BID for four weeks.
  • Observed clinical benefit in some patients, including partial tumor responses, especially in NSCLC. Median PFS of 31 weeks and OS of 60 weeks in 15 NSCLC patients.

Conclusions:

  • AXL1717 demonstrated an acceptable safety profile and promising efficacy in heavily pretreated patients.
  • AXL1717 showed particular promise in non-small cell lung cancer (NSCLC) patients.
  • Recommended phase II dose is 390 mg BID for four weeks. (NCT01062620)

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