A phase 1, open-label, dose-escalation study of olaratumab as a single agent and in combination with doxorubicin, vincristine/irinotecan, or high-dose ifosfamide in pediatric patients with relapsed or refractory solid tumors.

Abstract

TPS2599 Background: Olaratumab (LY3012207, IMC-3G3), a PDGFRα antagonist, is a targeted human IgG1 monoclonal antibody that specifically binds PDGFRα, blocking PDGF-AA, -BB, and -CC binding and receptor activation. Preclinical studies of olaratumab with or without chemotherapy have demonstrated antitumor activity in human sarcoma xenograft models. Positive survival outcomes were observed in adult patients with advanced soft tissue sarcoma when they were treated with olaratumab + doxorubicin vs doxorubicin alone in a randomized phase 2 trial. Methods: This multicenter clinical trial (NCT02677116) includes patients < 18 years of age with a diagnosis of relapsed or refractory solid tumors not amenable to curative treatment, for whom chemotherapy with doxorubicin, vincristine/irinotecan, or high-dose ifosfamide is deemed appropriate. The primary objective is to determine a recommended dose of olaratumab + ≥1 chemotherapy regimen(s) in pediatric patients based on any dose-limiting toxicity, and olaratumab serum exposure-matching between adult and pediatric patients. Secondary objectives include assessment of antitumor activity of each combination, immunogenicity, and pharmacokinetics. At least 12 pediatric patients will be treated with 1 cycle (21 days) of olaratumab monotherapy (dose level 1 [Part A] and dose level 2 [Part B]) on Days 1 and 8. If the patient does not experience a dose-limiting toxicity in the first cycle of monotherapy, the patient will then receive olaratumab plus either doxorubicin, vincristine/irinotecan, or high-dose ifosfamide per investigator discretion. Dose-limiting toxicity criteria will also be evaluated for the respective combinations in cycle 2. Treatment will continue until disease progression or other discontinuation criteria are met. Dose level 2 will be initiated after acceptable safety results from dose level 1 monotherapy (a minimum of 6 evaluable patients, and the pharmacokinetic profile). As of December 2016, enrollment is currently occurring in dose level 1. Clinical trial information: NCT02677116.