A Phase Ib study of telatinib (BAY 57-9352), a VEGFR-2 inhibitor, in combination with docetaxel in patients with advanced solid tumors

14035 Background: Telatinib (BAY 57–9352) inhibits VEGFR-2 and VEGFR-3 tyrosine kinases, and PDGFR-β and c-Kit. Preclinical data suggests that targeting VEGFR signaling increases antitumor activity. Methods: This trial investigated the safety, pharmacokinetics (PK), and tumor efficacy of telatinib combined with docetaxel (D). D was administered at a fixed dose of 75mg/m2 on day 1 of 21-day cycles. Telatinib was administered orally, twice daily (bid) from day 3 of Cycle 1 and onwards, thereafter continuously. Dosing of telatinib commenced at 600mg bid (cohort 1, n=6) and increased to 900mg bid (cohort 2, n=7). PK in Cycle 1 were determined on day 1 (D) and day 21 (telatinib). In Cycle 2 comparative PK profiles for both telatinib and D were sampled on days 1–3. Results: Thirteen patients (pts) with advanced solid tumors were enrolled (9M/4F; median age: 56 [range: 34–69]; ECOG PS 0/1: 3/10). A total of 69 cycles have been completed (range,1–10). Treatment-emergent adverse events of CTCAE =3 (NCI-CTC v3.0) were neutropenia (n=11, 79%), fever (n=2, 15%), and fatigue (n=2, 11%). Adverse events of CTC =3 occuring in two pts was febrile neutropenia. Others occurring in only one patient were; hypertension, ALT increase, dehydration, and reversible symptomatic pneumonitis. Study treatment-related adverse events leading to a dose reduction or interruption were neutropenia (n=5, 38%), hypertension (n=1), ALT increase (n=1), and fatigue (n=1). Two pts with prostate ca and 1 with cervical ca had a confirmed partial response. Five pts (1 NSCLC, 1 esophageal ca, 1 renal cell ca and 2 prostate ca) had stable disease for =4 cycles. Mean AUC of D increased by 48% in cohort 1, but only by 16% in cohort 2. Thus, PK data to date do not indicate a clear clinically relevant interaction between telatinib and D. Conclusions: The combination of telatinib and D was tolerated without reaching the toxic dose at telatinib 900mg bid and D 75mg/m2. This combination has demonstrated promising antitumor activity. An extension of the cohort at 900mg bid with 75mg/m2 D is being evaluated to gain further safety and PK data. No significant financial relationships to disclose.