A Phase I Dose-Escalation Study of Linsitinib (OSI-906), a Small-Molecule Dual Insulin-Like Growth Factor-1 Receptor/Insulin Receptor Kinase Inhibitor, in Combination with Irinotecan in Patients with Advanced Cancer
Mené sur 17 patients atteints d'un cancer de stade avancé réfractaire aux thérapies standards, cet essai de phase I évalue la dose maximale tolérée de l'irinotécan et du linsitinib, un inhibiteur ciblant IGF-1R
Background : This phase I dose‐escalation study was designed to evaluate the safety and tolerability of the combination of irinotecan and insulin‐like growth factor‐1 receptor (IGF‐1R) inhibitor linsitinib in patients with advanced cancer refractory to standard therapy. Methods : Dose escalation in three specified dose levels was performed according to a standard 3 + 3 design. Dose levels were as follows: (a) linsitinib 400 mg and irinotecan 100 mg/m2, (b) linsitinib 450 mg and irinotecan 100 mg/m2, and (c) linsitinib 450 mg and irinotecan 125 mg/m2. Linisitinib was administered once daily on days 1–3, 8–10, and 15–17, and irinotecan on days 1 and 8. Assessment of a candidate predictive biomarker was planned in all patients, with further evaluation in an expansion cohort of advanced colorectal cancer. Results : A total of 17 patients were treated, with 1 patient in both cohort 2 and 3 experiencing dose‐limiting toxicity. Linsitinib 450 mg and irinotecan 125 mg/m2 was the maximum tolerated dose. Sixteen (94%) patients experienced at least one treatment‐related adverse event. Neutropenia was the only grade >3 toxicity (4%). No significant hyperglycemia or QT interval prolongation was noted. No objective responses were observed; 47% (n = 8) had stable disease with median duration of 5.25 months. Conclusion : Although the combination was determined safe, the study was halted due to termination of linsitinib development, and biomarker testing was not performed