DILIGENCE-1: Dovitinib In 1st-Line Renal Cell Carcinoma, an Investigation into tumour GENe status and Correlation with Efficacy – 1st exploratory study — YRD
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  3. DILIGENCE-1: Dovitinib In 1st-Line Renal Cell Carcinoma, an Investigation into tumour GENe status and Correlation with Efficacy – 1st exploratory study

DILIGENCE-1: Dovitinib In 1st-Line Renal Cell Carcinoma, an Investigation into tumour GENe status and Correlation with Efficacy – 1st exploratory study (#33)

R Broom 1 2 , S Duffey 1 , K Thompson 1 , G Wilson 1 , F Hanning 1 , N Mitchell 1 , J Zwi 1 , M McKeage 1 2 , G Dranitsaris , P Oei 3 , P C Fong 1 2
  1. Auckland City Hospital, Auckland, New Zealand
  2. University of Auckland, Auckland, New Zealand
  3. IGENZ Ltd., Auckland

Purpose: Dovitinib is a multi-targeted tyrosine kinase inhibitor which, in addition to VEGFR blockade, also has affinity to FGFR-1,-2,-3 and PDGFRβ. It has demonstrated activity in heavily pre-treated patients with metastatic clear-cell renal cell carcinoma (mCCRCC). We sought to evaluate the activity of dovitinib in the first-line setting and correlate this activity with the status of genes relevant to the mechanism-of-action of dovitinib.

Methods: 30 treatment-naïve subjects with mCCRCC have been enrolled in this single-arm, single-site, phase II study. Key eligibility criteria included; ECOG PS 0-1, no prior systemic therapy for mCCRCC, adequate organ function, no active brain metastases and archival tissue available for gene status analysis. If metastatic tumour tissue was not available, then where possible, a biopsy was performed. Dovitinib was administered at 500mg 5 days on/2 days off until disease progression. An optional post-treatment biopsy (if feasible) was offered to subjects upon progression (and prior to commencement of 2nd-line therapy) with the aim of trying to elucidate mechanisms of resistance. The primary endpoint is PFS using RECIST 1.1. Secondary endpoints include response rate (RR) and efficacy by FGFR gene status (FISH and DNA sequence - Sequenom OncoCartaTM panel) by Spearman’s rho correlation coefficient.

Results: The first subject was enrolled in March 2012 and the 30th subject was enrolled February 2013. The median age of participants was 64 years and 72% were male. ECOG PS was 0 in 45% and 1 in 55%. Heng prognostic group was in favourable-risk in 38%, intermediate-risk in 52% and poor-risk in 10%. 38% of subjects had bone metastases at baseline. Four subjects were removed from study because of toxicity and one further subject was withdrawn (investigator decision), therefore target accrual has been increased to 31 subjects and is expected to complete May 2013. 93%, 59% and 51% of subjects enrolled have tumour tissue available for analysis from primary, metastatic and both sites respectively.

Conclusions: 30 subjects with mCCRCC have been treated 1st-line with dovitinib and in this setting this agent can be delivered safely. FGFR-1,-2,-3 and PDGF(Rβ) gene status and RR data will be available Q3 2013.