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