Phase Ii Study Of Bay 73-4506, A Multikinase Inhibitor, In Previously Untreated Patients With Metastatic Or Unresectable Renal Cell Cancer

5033 Background: BAY 73–4506 is an orally active, potent multikinase inhibitor targeting both tumor cell proliferation and tumor vasculature through inhibition of receptors of tyrosine kinases (VEGFR, KIT, RET, FGFR, and PDGFR) and serine/threonine kinases (RAF and p38MAPK). In tumor xenograft models, BAY 73–4506 demonstrated a broad spectrum of antitumor activity. The results of a phase I study (3 weeks on/1 week off schedule) indicated good tolerability and antitumor activity, including objective responses. Methods: Previously untreated patients with predominantly clear cell renal cell carcinoma (RCC) and measurable disease according to RECIST were enrolled in this multicenter, open-label, phase II study. Eligibility criteria included ECOG performance status 0–1, low or intermediate risk as per Motzer score, and adequate bone marrow and organ function. Treatment consisted of BAY 73–4506 160 mg once daily on a 3 weeks on/1 week off schedule. The primary end point was overall response rate. Results: 49 patients started treatment (accrual completed October 2008): 27 male, 22 female, median age 62 years (range 40–76). All patients were evaluable for safety, 33 patients are currently available for efficacy evaluation. The most common drug-related adverse events (all grades) reported in >20% of patients were hand-foot skin reaction (HFSR) (48%), fatigue (48%), hypertension (43%), mucositis (35%), dysphonia (33%), rash (30%), diarrhea (25%), and anorexia (23%). Grade 3–4 drug related toxicities (in >5% of patients) included HFSR (13%), rash (8%), fatigue (8%), and renal failure (8%). Renal failure occurred only in patients who continued taking study medication despite having inadequate fluid intake and/or diarrhea. Preliminary efficacy data of the 33 patients evaluable for response show a 27% partial response (PR) and a 42% stable disease (SD) rate. Further tumor assessments are scheduled for the patients (n = 35) remaining on study. Conclusions: Preliminary data show promising antitumor activity and good tolerability of BAY 73–4506 in patients with RCC. The observed toxicities were typical of the drug class and were manageable. Updated results will be presented at the meeting. [Table: see text]