Abstract 87P
Background
Dovitinib is a tyrosine kinase inhibitor that inhibits VEGFR1-3, PDGFR, FGFR1-3, c-KIT, FLT3 and topoisomerase 1 and 2. Dovitinib is in development with a tumor agnostic biomarker based on 58 genes associated with sensitivity and resistance to dovitinib. The most advanced development is in renal cell carcinoma (RCC), which is presented here.
Methods
A multinational phase 3 study enrolled 570 patients treated with either dovitinib or sorafenib in a ≥3rd line setting. Archival tumor samples were obtained from consenting patients to determine the predictive score in a prospective/retrospective design (pre-specified statistical analysis plan). The biomarker algorithm combines the expression of 58 mRNAs relevant to the in vitro sensitivity or resistance of dovitinib that include genes associated with FGFR, PDGF, VEGF, PI3K/Akt/mTOR and topoisomerase pathways as well as ABC drug transport and provides a likelihood score between 0-100%. A cut-point of the median of an RCC reference population was applied to make all statistical analysis categorical. A DRP Dovitinib score of > 67% was also applied.
Results
188 patients consented in the dovitinib group, of these 135 passed established biomarker quality criteria. The DRP-dovitinib divided the patients into two groups, sensitive (n=49, DRP score >50%) or resistant (n=86, DRP score ≤ 50%) to dovitinib. The DRP sensitive population was compared to the unselected sorafenib group (N=286). The HR for the median PFS and OS was 0.71 and 0.69, respectively (Table). The median PFS using a DRP-Dovitinib score of 67%, is 5.67 M (95% CI 1.87,20.34) HR=0.42 (95% CI 0.21,0.86) (p=0.0174) and the median OS is 20.6 M (95% CI; 9.53, 35.58) in the DRP selected group compared to sorafenib unselected (p=0.08) HR=0.55 (95% CI 0.28,1.08). Table: 87P
| Efficacy Parameter | Dovitinib Dovitinib Score >50% N=49 | Sorafenib Unselected N=286 | p-value | HR |
| Median PFS, Months (95% CI) | 3.75 (3.68, 5.39) | 3.61 (3.48,3.71) | 0.0572 | 0.71 (0.51,1.01) |
| Median OS, Months (95% CI) | 15.0 (12.94, 26.25) | 11.2 (9.66,13.37) | 0.04 | 0.69 (0.48,0.99) |
Conclusions
The DRP-Dovitinib can be used as a predictive biomarker and thus as a tool for the physician in identifying advanced RCC patients most likely to experiencing clinical benefit from dovitinib treatment.
Clinical trial identification
NCT01223027.
Editorial acknowledgement
Legal entity responsible for the study
Allarity Therapeutics.
Funding
Allarity Therapeutics.
Disclosure
R. Pili: Other, Personal, Advisory Role, Consultant: Amarex Clinical Research. S. Knudsen: Financial Interests, Personal, Officer: Allarity. K. Kazempour: Financial Interests, Personal, Officer: Amarex Clinical Resarch. H. Mekkonen: Other, Personal, Full or part-time Employment: Amarex Clinical Research. M. Foegh: Financial Interests, Personal, Officer: Allarity.