2367P - A randomized phase II study of atezolizumab (atezo) plus recombinant human IL-7 (CYT107) vs. atezo alone in patients with locally advanced or metastatic urothelial carcinoma (mUC)

Background

Atezolizumab is an anti-PD-L1 antibody that was approved for 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 addition of CYT107 would improve responses to PD-L1 inhibition by atezo. We performed a randomized trial (NCT03513952) in mUC comparing the combination of CYT107 and atezo to atezo alone.

Methods

Patients with mUC who had progressive disease after platinum-containing chemotherapy were screened. Key eligibility criteria included ECOG PS 0-2, measurable disease (by RECIST 1.1), and no prior checkpoint inhibitor or cytokine immunotherapy. A safety run-in using the combination of CYT107 and atezo was performed, 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 including clinical benefit rate, PFS, DOR, OS, and safety. Detailed immune response analysis and exploratory correlative analyses are in progress.

Results

A total of 47 patients were enrolled. Patient demographics between arms were well-balanced. ORR was 26.3% for the combination vs 23.8% for atezo alone (p=0.43). There were no significant differences in clinical benefit rate, PFS, DOR, or OS. No dose limiting toxicities were seen in the safety run-in cohort (n=7). 76.9% (20/26) of patients on the CYT107 arm received all four doses. The combination of CYT107 and atezo was well tolerated compared to the atezo arm, with overall grade 3-4 adverse events (AEs) occurring in 46.2% (12/26) and 63.2% (12/19), respectively. Immune-mediated AEs of any grade occurred in 50% (13/26) vs 68.4% (13/19), respectively. 6.3% vs 17.6% of patients on the combination vs monotherapy arm discontinued therapy due to toxicity.

Conclusions

This is the first randomized trial of atezolizumab +/- 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 During the trial, the FDA approval for atezo in mUC was withdrawn, which limited enrollment.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, although there was no improvement in clinical outcomes compared to atezo monotherapy.

Clinical trial identification

NCT03513952.

Editorial acknowledgement

Legal entity responsible for the study

Cancer Immunotherapy Trials Network (CITN).

Funding

National Cancer Institute of the National Institutes of Health.

Disclosure

R. Pachynski: Financial Interests, Personal, Advisory Board: Bayer, Janssen, Dendreon, EMD Serono, Genomic Health, Jounce, Pfizer, BMS; Financial Interests, Personal, Invited Speaker: AstraZeneca, Genentech/Roche, Sanofi; Financial Interests, Personal, Advisory Board, Liquid biopsy for prostate cancer: Tempus Labs; Financial Interests, Institutional, Funding: Janssen, Pharmacyclics; Financial Interests, Steering Committee Member: BMS; Non-Financial Interests, Principal Investigator: BMS, Merck, ESSA, Janssen, Pfizer/EMD Serono, ESSA, Ambrx, Amgen. R.K. Jain: Financial Interests, Personal, Advisory Board: BMS, Gilead, Seattle Genetics, Aveo, EMD Serono; Financial Interests, Personal, Invited Speaker: Seattle Genetics, DAVA Oncology; Financial Interests, Institutional, Research Grant: BMS, Gilead. H. Moon: Financial Interests, Institutional, Coordinating PI, clinical trial PI: Seagen; Financial Interests, Personal and Institutional, Steering Committee Member, Steering Committee: EMD Serono; Financial Interests, Institutional, Coordinating PI, PI for Clinical trial: Janssen; Financial Interests, Institutional, Coordinating PI, PI for Trial: Nektar; Financial Interests, Coordinating PI, Clinical trial PI: Huya; Non-Financial Interests, Other, Grant Proposal Review committee for NCCN/Pfizer Bladder cancer grant review committee: NCCN; Non-Financial Interests, Advisory Role, NCI Prostate Cancer task force: NCI. R. Sweis: Financial Interests, Personal, Advisory Board: Aduro, Astellas, AstraZeneca, BMS, EMD Serono, Editas, Exelixis, Eisai, Janssen, Mirati, Pfizer, Silverback, Seattle Genetics; Financial Interests, Personal, Invited Speaker: Aveo; Financial Interests, Personal, Stocks/Shares: AbbVie; Financial Interests, Institutional, Local PI: AbbVie, Aduro, Ascendis, Astellas, BMS, Bayer, CytomX, Eisai, Genentech/Roche, Immunocore, Merck, Mirati, Moderna, Novartis, QED, Pyxis Oncology, ALX Oncology; Financial Interests, Institutional, Research Grant: Epivax. S.P. Fling: Financial Interests, Institutional, Funding, Industry provided funds in salary support and research for CITN clinical trials: Merck, Revimmune. A. Lacroix: Financial Interests, Personal, Other, Consultant for the Cancer Immunotherapy Trials Network: Fred Hutchinson Cancer Research Center. E. Yu: Financial Interests, Personal, Advisory Board: Janssen, Merck, Advanced Accelerator Applications, Novartis, Bayer, Aadi Bioscience; Financial Interests, Personal, Other, Scientific Advisory Board: Oncternal; Financial Interests, Institutional, Local PI: Daiichi Sankyo, Taiho, Surface; Financial Interests, Institutional, Coordinating PI: Dendreon, Merck, Seagen, Blue Earth, Bayer, Lantheus. All other authors have declared no conflicts of interest.