Potential impact of avelumab+axitinib (A+Ax) on tumor size (TS) compared with historical data of sunitinib (S) as evaluated by a modeling and simulation (MS) approach

Abstract

Background: Combining an immune checkpoint inhibitor (A) with a targeted VEGF antiangiogenic agent (Ax) may leverage complementary mechanisms of action for treatment of metastatic renal cell carcinoma (mRCC). JAVELIN Renal 100 is a phase (Ph) 1b trial evaluating the clinical activity and safety of A+Ax in treatment‐naïve patients (pts) with mRCC. An early evaluation of the effect of A+Ax on TS, i.e. sum of diameters for target lesions, compared to historical S, the standard of care1, can inform on decisions for future drug development for A+Ax. Claret et al. have shown that a greater early TS reduction at week 8 of treatment (TR8) is correlated with a longer progression free survival time in trials of 1st line treatment of mRCC2. The objective of this analysis is to apply MS methodology to data from JAVELIN Renal 100 to evaluate the potential effect of A+Ax on TS as compared to historical S data. Methods: A tumor dynamic model3 was applied to the longitudinal TS data obtained from the Ph1b study of A+Ax and from the historical Ph3 trial of S. The model includes 3 parameters representing the rate of tumor growth (KL), the rate of drug effect in reducing tumor size (KD), and the rate of the loss of drug effect (DM). The TR8 for each patient can be derived from the model. A larger KD, smaller DM, and TR8 suggested a greater effect. The parameters and TR8 from the two treatments are estimated and compared using ANOVA. Results: The summaries of the model parameters, TR8, and p‐value of ANOVA analysis are presented in the Table below: Conclusions: MS is an effective tool to inform drug development. These results suggest that A+Ax results in a greater TS reduction than S, supporting further investigation of A+Ax vs S in the JAVELIN 101 randomized Ph3 trial. References: 1. Motzer R et al NEJM (2007) 356:115 2. Claret L et al Cancer Chemother Pharmacol (2016) 78:605 3. Claret L et al PAGE 2012 Abstr 2328. (Table Presented).