Abstract | PURPOSE: METHODS: Patients were enrolled into five dose-escalating cohorts of 3-6 patients each. Olaratumab was administered intravenously weekly at 4, 8, or 16 mg/kg (cohorts 1-3) or once every other week at 15 or 20 mg/kg (cohorts 4-5), with 4 weeks/cycle. RESULTS: Nineteen patients were treated in five cohorts. There were no dose-limiting toxicities; the MTD was not identified with the doses studied. The most common olaratumab-related adverse events (AE) were fatigue and infusion reactions (10.5 % each). With the exception of 1 patient (20 mg/kg) experiencing two grade 3 drug-related AEs after the dose-limiting toxicity assessment period, all drug-related AEs were grade 1 or 2. The trough concentrations (C min) for 16 mg/kg weekly and 20 mg/kg biweekly were higher than 155 μg/mL, and the concentration found to be efficacious in preclinical xenograft models. Twelve patients (63.2 %) had a best response of stable disease [median duration of 3.9 months (95 % CI 2.3-8.7)]. CONCLUSIONS:
Olaratumab was well tolerated and showed preliminary antitumor activity. RP2Ds are 16 mg/kg weekly and 20 mg/kg biweekly. Phase II studies of olaratumab as monotherapy and in combination are ongoing in several tumor types.
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Authors | E Gabriela Chiorean, Christopher Sweeney, Hagop Youssoufian, Amy Qin, Aruna Dontabhaktuni, Nick Loizos, Johannes Nippgen, Robert Amato |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 73
Issue 3
Pg. 595-604
(Mar 2014)
ISSN: 1432-0843 [Electronic] Germany |
PMID | 24452395
(Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Antineoplastic Agents
- Receptor, Platelet-Derived Growth Factor alpha
- olaratumab
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Topics |
- Aged
- Aged, 80 and over
- Antibodies, Monoclonal
(administration & dosage, adverse effects, metabolism, pharmacokinetics)
- Antineoplastic Agents
(administration & dosage, adverse effects, pharmacokinetics)
- Cohort Studies
- Dose-Response Relationship, Drug
- Drug Administration Schedule
- Female
- Humans
- Male
- Middle Aged
- Neoplasms
(drug therapy, metabolism)
- Receptor, Platelet-Derived Growth Factor alpha
(immunology)
- Treatment Outcome
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