Background: CRP is an important prognostic and predictive factor in patients with aRCC receiving various therapies, such as cytokines and tyrosine kinase inhibitors. In this extended follow-up to the phase 3 JAVELIN Renal 101 trial (NCT02684006), we report the association of CRP levels at baseline (BL) and early after treatment with the efficacy of A + Ax or sunitinib (S). Methods: CRP levels were assessed at screening and day 1 of each 6-week cycle. Patients were categorized into CRP normal (BL CRP < 10 mg/L), normalized (BL CRP ≥10 mg/L and ≥1 CRP value decreased to < 10 mg/L during 6 weeks of treatment), and non-normalized (CRP ≥10 mg/L at BL and during 6 weeks of treatment) groups. Multivariate analysis of BL characteristics, including CRP for efficacy, was also conducted. Progression-free survival (PFS) and best overall response per independent central review (RECIST 1.1) from the second interim analysis (IA2) of overall survival (OS) and OS from the third interim analysis (IA3) were assessed. Results: Minimum duration of follow-up for IA2 and IA3 were 13 and 28 months, respectively. The table shows objective response rate (ORR), PFS, and OS by CRP group. Efficacy outcomes in the normal and normalized groups were favorable compared with the non-normalized group with both A + Ax and S. In the A + Ax arm, the complete response rate was 11.8% (normalized group), 3.8% (normal group), and 0.9% (non-normalized group). With A + Ax, the PFS in the normalized group was longer than in the normal group, but this was not observed with S. In each CRP group, all efficacy outcomes were favorable with A + Ax vs S. In the multivariate analysis, normalized or non-normalized CRP was an independent predictive factor of ORR or OS with A + Ax. Conclusions: Normal and normalized CRP levels were associated with improved A + Ax efficacy. A + Ax demonstrated favorable efficacy across CRP groups. OS in this study was immature; follow-up for the final analysis is ongoing. Further research in defining predictive value of CRP is warranted. Clinical trial information: NCT02684006

HR, hazard ratio; m, median; NE, not estimable; Ref, reference. *Unstratified.