3048 Background: GW572016 is a small molecule tyrosine kinase inhibitor that interrupts both EGFR and ErbB2 signal transduction pathways. To evaluate safety, pharmacokinetics and antitumor activity, and to determine the recommended dose of GW572016, a phase I study was conducted in patients (pts) with advanced solid tumors in Japan. METHODS GW572016 was administered orally once daily until pts had disease progression or unacceptable toxicities. A cohort of 6 pts was treated at 900, 1200, 1600, and 1800 mg/day. Grade 3 toxicities were considered dose limiting, and the maximum tolerated dose (MTD) was a dose at which 2 of 6 pts had grade 3 toxicities. Pharmacokinetics was evaluated on days 1 and 21. RESULTS Grade 1-2 rash, diarrhea, anorexia, fatigue, stomatitis, nausea and vomiting were the most frequent adverse events. Because 2 patients at 1800 mg/day experienced grade 3 diarrhea (one of them also had grade 3 elevation of GGT), the MTD was 1800 mg/day. The steady state concentration of GW572016 in serum increased with dose; 820±448 and 1899±1356 ng/mL at 1200 and 1600 mg, respectively. These concentrations exceeded the IC50 values for in vitro tumor cell growth. The pharmacokinetic profiles in Japanese pts were similar to those of Western pts. Two pts had partial responses (PRs) by RECIST; a pt with trastuzumab-resistant breast cancer (Her2, 3+; ER/PgR, negative) at 1600 mg/day, and a male pt with squamous cell carcinoma of the lung at 900 mg/day. Twelve pts (6 non-small cell lung cancers, 3 colorectal cancers, breast cancer, cervical cancer, and ovarian cancer) had stable disease (SD). In PR and SD pts, 8 pts continued treatment for more than 3 months. Standardized uptake values (SUV) measured by PET decreased significantly in two patients; one with breast cancer in which SUV was reduced by 60% had PR, and another with colorectal cancer in which SUV was reduced by 42% had SD for more than 8 months. CONCLUSIONS GW572016 was well tolerated when administered orally in doses from 900 mg/day to 1600 mg/day once daily, with preliminary evidence of anti-tumor activity in heavily pretreated patients. Phase II studies are warranted, and 1600 mg/day or less is recommended based on the results of this study. No significant financial relationships to disclose.