A Phase II Study of the Efficacy and Safety of Axitinib (Axi) Given on an Individualized Schedule for metastatic renal cell carcinoma (mRCC) after treatment with PD-1 / PD-L1 Inhibitors NCT02579811

Axitinib is a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) approved for the treatment of mRCC after failure of 1 systemic therapy. Pharmacokinetics (PKs) demonstrate significant inter-patient variability, and clinical data indicate that higher exposure is associated with improved clinical outcomes.^1,2 The current-recommended Axi titration from 5mg to 7mg to 10mg BID is often not tolerated by many patients (pts). As such, many pts do not undergo dose-titration resulting in lower than necessary drug plasma levels. Further, no prospective data exists on the efficacy of Axi in the post-PD-1/PD-L1 setting. This study aims to identify a more individualized dose-titration algorithm and to prospectively assess the clinical efficacy of Axi after PD-1/PD-L1 inhibition.

Eligibility criteria include clear cell mRCC following progression on PD-1/PD-L1 therapy, measurable disease, and adequate organ function. Pts will be treated with Axi 5mg BID, with dose titration in 1mg increments every 14 days if no grade (G) 2 Axi-related mucositis, diarrhea, hand-foot-syndrome, or fatigue (other toxicities are not considered). Instead of dose reduction for G2 adverse events (AEs), pts will have a brief break (i.e. 3 days per physician discretion), then resume the same dose if AE becomes G1 or less. Dose reduction in 1mg increments will be done for recurrent G2 AEs in spite of treatment break, and per physician discretion. The intent is to rapidly titrate Axi with smaller dosing increments and utilize occasional, brief breaks in order to maximize dose intensity with tolerable AEs. Response will be assessed by standard imaging studies every 8 weeks. To date, 24/50 pts have been enrolled, with the goal of 44 evaluable pts to test the hypothesis that individualized dose titration will lead to 40-45% increase in median PFS (from 7 to 10 months) in the post PD-1 / PD-L1 inhibitor setting.