Phase I study of olaratumab in Japanese patients with advanced solid tumors.

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Doi T, Ma Y, Dontabhaktuni A, Nippgen C, Nippgen J, Ohtsu A

Phase I study of olaratumab in Japanese patients with advanced solid tumors.

Cancer Sci. 2014 Jul;105(7):862-9. doi: 10.1111/cas.12444. Epub 2014 Jun 27.

PubMed ID

24816152 [ View in PubMed

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Abstract

Olaratumab (IMC-3G3) is a fully human IgG1 monoclonal antibody that selectively binds the external domain of human platelet-derived growth factor receptor-alpha with high affinity and blocks ligand binding. This was a single-center, dose-escalation, phase I trial of olaratumab in Japanese patients with advanced/refractory solid malignancies. Three to six patients were enrolled into each of three cohorts: Patients received i.v. olaratumab: 10 mg/kg on days 1 and 8 every 3 weeks (cohort 1); 20 mg/kg every 2 weeks (cohort 2); and 15 mg/kg on days 1 and 8 every 3 weeks (cohort 3). Doses were escalated from cohort 1 through cohort 3. The primary objective was to establish the safety and pharmacokinetic profile of olaratumab. Sixteen patients were treated across three cohorts. There were no dose-limiting toxicities, so the maximum tolerated dose was not reached. The most common olaratumab-related treatment-emergent adverse events (TEAEs) were proteinuria (25.0%) and elevated aspartate transaminase (12.5%). One patient (cohort 2) had two olaratumab-related Grade 3 TEAEs (increased aspartate aminotransferase and tumor hemorrhage); otherwise, olaratumab-related TEAEs were Grade 1/2. Seven patients (43.8%) had a best response of stable disease. Based on the pharmacokinetic concentration profile of olaratumab, the trough concentrations following single and multiple doses at 15 mg/kg on days 1 and 8 every 3 weeks (cohort 3) and multiple doses at 20 mg/kg every 2 weeks (cohort 2) were above the 155 mug/mL target. Thus, these two doses could represent an acceptable schedule for future trials in Japanese patients. Olaratumab had an acceptable safety profile and was well tolerated.

DrugBank Data that Cites this Article

Drugs

Olaratumab

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Olaratumab	Platelet-derived growth factor receptor alpha	Protein	Humans	Yes	Antagonist	Details