Olaratumab, a monoclonal antibody targeting human platelet-derived growth factor 
receptor α, plus doxorubicin significantly improved overall survival in patients 
with advanced soft-tissue sarcoma (STS) in a prior phase 1b/2 randomized trial. 
Subsequent exposure-response analysis suggested that higher olaratumab exposures 
earlier might improve outcomes in patients at risk of early disease progression. 
This phase 1 study (3 treatment cohorts; minimum 6 patients each) investigated 
the safety, pharmacokinetics and antitumor activity of olaratumab plus 
doxorubicin in Japanese patients with STS. Patients received olaratumab 15 mg/kg 
on Days 1 and 8 during each 21-day cycle until disease progression. Patients in 
Cohort 3 received a 20 mg/kg loading dose of olaratumab in Cycle 1. Doxorubicin 
was administered for up to 6 cycles. Patients in Cohort 1 received doxorubicin 
25 mg/m2 on Days 1, 2 and 3. Patients in Cohorts 2 and 3 received doxorubicin 
75 mg/m2 on Day 1. One patient in Cohort 2 experienced a dose-limiting toxicity 
of Grade 3 febrile neutropenia. Most treatment-emergent adverse events were of 
mild and moderate severity, and were known doxorubicin toxicities. Olaratumab 
serum concentrations in Cohort 3 reached a steady-state exceeding the target 
level in Cycle 1. Partial response was confirmed in 4 patients (2 each in 
Cohorts 2 and 3). Olaratumab plus doxorubicin had an acceptable safety profile 
in patients with STS. A loading dose of olaratumab 20 mg/kg was effective for 
achieving minimum serum concentrations above the target trough level in Cycle 1.