A phase 1 study of OSI-930 in combination with erlotinib in patients with advanced solid tumours

Eur J Cancer. 2013 Mar;49(4):782-9. doi: 10.1016/j.ejca.2012.09.036. Epub 2012 Oct 22.


Aim: To determine the maximum tolerated dose (MTD) of OSI-930 that can be combined with erlotinib, and establish recommended phase 2 doses when both agents are administered daily in patients with advanced solid tumours.

Patients and methods: Eligible patients with advanced solid tumours were enrolled into this standard "three+three" dose escalation study. Study treatment commenced on day 1 with OSI-930, and erlotinib was introduced on day 8. PK profiles of OSI-930, erlotinib and its active metabolite, OSI-420, were determined. Changes in sVEGFR2 as a pharmacodynamic biomarker of OSI-930 activity were assessed.

Results: Twenty one patients were enrolled to 1 of 3 cohorts: 200 mg OSI-930 BID+100 mg erlotinib QD; 200 mg OSI-930 BID+150 mg erlotinib QD; 300 mg OSI-930 BID+150 mg erlotinib QD. The most common adverse events were anorexia (85%), diarrhoea (75%), rash (70%) and lethargy (65%). The MTD was not reached but the onset of cumulative toxicity necessitating dose modification after the 28-d DLT assessment period was common at the highest dose level. A PK interaction was identified with co-administration of both agents resulting in a two-fold increase in OSI-930 exposure. Pharmacodynamic activity was observed with a decline in sVEGFR levels detected in all patients. Ten patients had disease stabilization (median duration 119 d).

Conclusions: 200 mg OSI-930 BID+150 mg erlotinib QD were the recommended doses for further evaluation of this combination.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols
  • Area Under Curve
  • Dose-Response Relationship, Drug
  • ErbB Receptors / antagonists & inhibitors
  • Erlotinib Hydrochloride
  • Female
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasms / drug therapy*
  • Prognosis
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / pharmacokinetics
  • Quinazolines / therapeutic use*
  • Quinolines / pharmacokinetics
  • Quinolines / therapeutic use*
  • Thiophenes / pharmacokinetics
  • Thiophenes / therapeutic use*
  • Tissue Distribution


  • OSI 930
  • Protein Kinase Inhibitors
  • Quinazolines
  • Quinolines
  • Thiophenes
  • Erlotinib Hydrochloride
  • ErbB Receptors