Background: The phase 3 JAVELIN Renal 101 trial ( NCT02684006 ) demonstrated significantly improved progression-free survival (PFS) with first-line avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma (aRCC). We report updated efficacy data from the second interim analysis. Patients and methods: Treatment-naive patients with aRCC were randomized (1 : 1) to receive avelumab (10 mg/kg) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were PFS and overall survival (OS) among patients with programmed death ligand 1–positive (PD-L1+) tumors. Key secondary end points were OS and PFS in the overall population. Results: Of 886 patients, 442 were randomized to the avelumab plus axitinib arm and 444 to the sunitinib arm; 270 and 290 had PD-L1+ tumors, respectively. After a minimum follow-up of 13 months (data cut-off 28 January 2019), PFS was significantly longer in the avelumab plus axitinib arm than in the sunitinib arm {PD-L1+ population: hazard ratio (HR) 0.62 [95% confidence interval (CI) 0.490–0.777]}; one-sided P < 0.0001; median 13.8 (95% CI 10.1–20.7) versus 7.0 months (95% CI 5.7–9.6); overall population: HR 0.69 (95% CI 0.574–0.825); one-sided P < 0.0001; median 13.3 (95% CI 11.1–15.3) versus 8.0 months (95% CI 6.7–9.8)]. OS data were immature [PD-L1+ population: HR 0.828 (95% CI 0.596–1.151); one-sided P = 0.1301; overall population: HR 0.796 (95% CI 0.616–1.027); one-sided P = 0.0392]. Conclusion: Among patients with previously untreated aRCC, treatment with avelumab plus axitinib continued to result in a statistically significant improvement in PFS versus sunitinib; OS data were still immature. Clinical Trial number: NCT02684006 .

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association of these sigs with efficacy in the phase 3 KEYNOTE-045 trial of pembro vs chemo in platinum-refractory metastatic UC (mUC).Methods: Univariate analyses using logistic regression (ORR) and Cox proportional hazard (PFS, OS), adjusted for ECOG PS, were performed, and nominal P values (1sided, pembro; 2-sided, chemo) without multiplicity adjustment were calculated. Significance was prespecified at 0.05. Clinical utility of GEP and stromal sig was assessed using first tertile and median cutoffs.Results: 291/542 pts (53.7%) had RNA-seq data. GEP was associated with ORR (P¼0.05) with pembro; a positive trend was observed for PFS (P¼0.09) and OS (P¼0.12). GEP was not associated with ORR (P¼0.87), PFS (P¼0.58), or OS (P¼0.98) with chemo. HR estimates using prespecified GEP cutoff suggest trends toward improved PFS and OS for pembro vs chemo in GEP-high group (Table ). Stromal sig was not associated with outcomes with pembro (P¼0.15 [ORR], 0.30 [PFS], 0.40 [OS]) or chemo (P¼0.42 [ORR], 0.09 [PFS], 0.12 [OS]). HR estimates using prespecified stromal sig cutoff suggest trends toward longer PFS and OS in median group; this may be driven by poor performance of chemo in this group vs the hypothesized association with pembro (Table ). Conclusions:In this exploratory analysis in pts with mUC from KEYNOTE-045, GEP was positively associated with ORR to pembro but not chemo. GEP continues to serve as a good exploratory gene sig to support the MOA of pembro in highly inflamed tumors. Stromal sig was not associated with outcomes to pembro in KEYNOTE-045. Additional analyses are exploring differences in association of stromal sig with pembro between KEYNOTE-052 and KEYNOTE-045.Clinical trial identification: NCT02256436.

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