Randomized phase 2 trial of atezolizumab with or without human recombinant IL-7 for advanced urothelial cancer

Advanced urothelial cancer (aUC) generally has high mortality despite modern anti-PD-(L)1 antibody-based combinations. Augmenting checkpoint inhibitor-mediated immune responses with lymphocyte growth factors may improve outcomes. A multicenter phase 2 trial in the USA randomized aUC patients to atezolizumab alone or in combination with human recombinant IL-7 (CYT107) weekly for four doses. The combination was well tolerated, without dose-limiting toxicities, and lower frequency of grade 3 or 4 treatment-related adverse events compared to atezolizumab monotherapy. The objective response rate (ORR) was not significantly different between the groups (26.3% with the combination and 23.8% with atezolizumab alone). The complete response rate (CRR) was 10.5% with the combination and 4.8% with monotherapy. Three patients in the combination group and one patient in the monotherapy group had responses longer than 21 months. CD4+ and CD8+ T lymphocyte expansion occurred in patients with response to the combination. The authors conclude that combining CYT107 with atezolizumab was safe and resulted in lymphocyte expansion, doubling of the CRR, and durable responses; however, the ORR was not significantly improved. Increased and sustained doses of CYT107 should be further investigated.