4523 Background: In the phase II study B2222, 147 pts with unresectable/metastatic GIST were randomized 1:1 to receive imatinib (IM) at 400 vs 600 mg daily. The estimated survival rate at 60 months was 47.6%. We report the PK of IM and the correlation of IM levels with clinical response. Methods: The IM plasma levels were analyzed in a subset of pts (n=73) for whom PK data on day 1 of treatment or at steady state (Day 29) was available (n=34 and 39 for 400 and 600 mg/day, respectively). IM PK was evaluated using a population PK approach. A correlation between IM plasma exposure and clinical outcome was explored by grouping pts into quartiles according to IM trough levels at steady state (Cmin). The clinical outcome parameters evaluated include overall objective responses (OOR=CR+PR), time to progression (TTP), and KIT mutation status. Results: Clinical response tended to correlate with IM trough exposure. OOR was achieved by 8 of 18 (44%) pts in Q1 (Cmin <1,110 ng/mL) compared with 24 of 36 (67%) and 14 of 19 (74%) in Q2-Q3 (≥1,110 - <2,040 ng/mL), and Q4 (≥2,040 ng/mL), respectively (p=0.060 for Q1 vs Q2-Q4). The median TTP was 11.3 months for pts in Q1 and over 30 months for Q2-Q4 (p=0.0029). In pts with GIST with exon 11 KIT mutation (n=39), the OOR was 55.6% for Q1 vs 93.3% for Q2-Q4 (p=0.006). The IM plasma AUC, peak concentration, and Cmin were highly correlated, with IM Cmin having the best correlation with response. Conclusions: Exposure to adequate drug levels of IM appears to correlate with clinical benefit; pts with the lowest IM levels show the lowest OOR and shortest TTP. These results suggest that monitoring IM exposure may be important for optimal clinical outcome. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Infinity, MedImmune, Novartis, Pfizer Novartis MedImmune, Novartis, Pfizer Infinity, Novartis, Pfizer Infinity, Novartis, Pfizer