A randomized phase II study of atezolizumab (atezo) plus recombinant human IL-7 (CYT107) in patients with locally advanced or metastatic urothelial carcinoma.
Authors: Pachynski Russell Kent , Chatta Gurkamal S. , Jain Rohit K. , Moon Helen H. , Sweis Randy F. , Delacroix Scott Edward , Fang Alana , D'amico Leonard A. , Kask Angela Shaulov , Fling Steven P. , Lacroix Andreanne , Kaiser Judith C. , Sharon Elad , Yu Evan Y. 
Published: January 2024

628 Background: Atezolizumab (atezo) is an anti-PD-L1 antibody that was approved for use in patients with mUC following platinum-containing regimens. IL-7 (CYT107) is a homeostatic cytokine that supports the proliferation and persistence of T cells. We hypothesized that combining CYT107 with atezo would improve responses in mUC patients. Methods: To test this, we performed a randomized trial (NCT03513952) comparing the combination of CYT107/atezo to atezo alone in patients with mUC previously treated with a platinum regimen. Key eligibility criteria included ECOG PS 0-2, measurable disease (RECIST 1.1), and no prior systemic immunotherapy. A safety run-in using CYT107/atezo was performed (n=7), followed by randomization 1:1 to atezo 1200 mg IV q3wks +/- CYT107 10 ug/kg IM qwk X 4. The primary endpoint was objective response rate (ORR), with secondary endpoints of clinical benefit rate, PFS, DOR, OS, and safety, with a number of exploratory correlative analyses. Results: A total of 47 patients were enrolled. Patient demographics between arms were well-balanced. No dose limiting toxicities (DLTs) were seen. Overall, the combination of CYT107/atezo was well tolerated compared to the atezo monotherapy arm, with overall grade 3-4 (G3-4) adverse events (AEs) occurring in 46.2% (12/26) and 63.2% (12/19) of patients, respectively. Rates of treatment-related events were: Any (80.8% vs 73.7%), G1-2 (65.4% vs 36.8%), and G3-4 (15.4% vs 36.8%) in CYT107/atezo vs monotherapy arms, respectively. Treatment-related immune-mediated AEs of any grade occurred in 50% (13/26) of patients in combination arm vs 68.4% (13/19) in monotherapy arm. 0% vs 17.6% of patients on the combination vs monotherapy arm discontinued therapy due to toxicity, respectively. ORR was 26.3% vs 23.8% in the combination vs monotherapy arm (p=0.43), respectively. Complete responses (CR) were seen in 10.5% (2/19) and 4.8% (1/21), and partial responses seen in 15.8% (3/19) and 19% (4/21) of patients in the combination vs monotherapy arms, respectively. There were no significant differences in clinical benefit rate (36.8% vs 42.9%), PFS (2.3 vs 2.2 mos), or OS (9.1 vs 10.4 mos). Rapid expansion of T cells was observed (~1.7-fold by day 8 following first dosing) in the CYT107/atezo arm only. Expansion peaked earlier for CD4s (~2-fold, day 22) and later for CD8s (~2.1-fold, day 29) and was maintained above baseline through C6D01. Detailed T cell subset pharmacodynamic data will be presented. Conclusions: This is the first randomized trial of atezo +/- IL-7 (CYT107) in mUC. During the trial, the FDA approval for atezo in mUC was withdrawn, which limited enrollment. However, our results show that the addition of CYT107 to atezo is safe/tolerable, with comparable toxicity profile and efficacy to monotherapy. Clinical trial information: NCT03513952 .