874P - Immune Correlates for the Efficacy of PEGylated Human IL-10 (AM0010) with Nivolumab in Renal Cell Cancer

Date 10 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Renal Cell Cancer
Cancer Immunology and Immunotherapy
Genitourinary Cancers
Presenter Aung Naing
Citation Annals of Oncology (2017) 28 (suppl_5): v295-v329. 10.1093/annonc/mdx371
Authors A. Naing1, J.R. Infante2, D.J. Wong3, M.W. Korn4, R. Aljumaily5, K. Papadopoulos6, K. Autio7, S. Pant8, T.M. Bauer9, A. Drakaki10, N. Daver11, A. Hung12, P. Van Vlasselaer12, G. Brown12, M. Oft12, N. Tannir13
  • 1Medical Oncology, MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 2Medical Oncology, Sarah Cannon Research Institute/Tennessee Oncology, 37203 - Nashville/US
  • 3Department Of Medicine, University of California, Los Angeles, 90024 - Los Angeles/US
  • 4Cancer Center, UCSF, 94158 - San Francisco/US
  • 5Hematology/oncology, Oklahoma University Medical Centre, Oklahoma City/US
  • 6Oncology, South Texas Accelerated Research Therapeutics (START), 78229 - San Antonio/US
  • 7Genitourinary Oncology, MSKCC, 10065 - New York/US
  • 8Oncology, College of Pharmacy, OUHSC, 73117 - Oklahoma City/US
  • 9Drug Development Unit, Sarah Cannon Research Institute/Tennessee Oncology, Nashville/US
  • 10Medicine And Urology, UCLA Medical Center, Los Angeles/US
  • 11Cancer Center, MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 12Clinical Development, ARMO BioSciences, 94063 - Redwood City/US
  • 13Cancer Center, MD Anderson Cancer Center, 77030-3721 - Houston/US

Abstract

Background

At therapeutic concentrations AM0010 stimulates the cytotoxicity, survival and proliferation of CD8 T cells. IL-10 receptors and PD-1 are expressed on activated and exhausted CD8 T cells, providing a rationale for combining AM0010 and an anti-PD-1. AM0010 alone had partial tumor responses (PR) in 4 of 16 pts with poor to intermediate risk RCC. In dose escalation, 4 of 8 RCC patients receiving AM0010 plus pembrolizumab in 3rd line, had a PR. The mPFS was 16.7 months.

Methods

29 pts with metastatic RCC were enrolled on AM0010 (10 or 20 ug/kg daily SC) and nivolumab (3mg/kg, q2wk IV). Two had favorable, 20 had intermediate and 4 had poor IMDC risk (3 data not available). Pts. had a median of 1 prior therapy (range 1-3), and at least one VEGFR-TKI. Tumor responses were assessed following irRC. Immune related cytokines in the serum, activation of blood derived T cells and clonal identity of peripheral T cell were measured.

Results

AMO010 plus nivolumab or pembrolizumab was well tolerated. TrAEs were reversible and transient. 14 patients on 20ug/kg AM0010 daily SC and nivolumab had at least 1 G3/4 TrAE, including anemia (10), thrombocytopenia (5), hypertriglyceridemia (5). Two pts had a reversible cytokine release syndrome with splenomegaly and increased immune mediated red blood cell phagocytosis most likely precipitated by T-cell activation, as both pts had objective tumor responses. Patients treated with 10ug/kg AM0010 and anti-PD-1 did not have hematologic G3/4 TrAEs. As of May 1 2017, PRs were observed in 9 of 26 evaluable pts (35%). An additional 12 pts have stable disease (46%), 7 of those have a tumor reduction > 30% (in progress). The mPFS and mOS has not been reached, the mFU is 7.7 months (range 0.5-13.7). AM0010 + anti-PD1 increased Th1 cytokines in the serum, proliferation of PD1+ Lag3+ CD8 T cells and oligoclonal expansion of novel T cell clones in the blood. The expansion of invigorated T cells and the clonal expansion correlated with tumor responses.

Conclusions

AM0010 in combination with anti-PD-1 is well-tolerated in RCC pts, the recommended phase 2 dose is 10ug/kg. The efficacy and the observed CD8 T cell activation is promising and encourages the continued study of AM0010 in combination with nivolumab.

Clinical trial identification

NCT02009449

Legal entity responsible for the study

ARMO BioSciences

Funding

ARMO BioSciences

Disclosure

A. Hung: Stock employment. P. Van Vlasselaer: Employment stock ledership. M. Oft: Employment. All other authors have declared no conflicts of interest.