9PD - PEGylated human IL-10 (AM0010) in Combination with an anti-PD-1 in Advanced NSCLC (9PD)

Date 09 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Poster Discussion session
Topics Biomarkers
Cancer in Pregnancy
Familial Cancer
Cancer in Special Situations
Presenter Deborah Wong
Citation Annals of Oncology (2017) 28 (suppl_11): xi3-xi5. 10.1093/annonc/mdx710
Authors D. Wong1, J.G. Schneider2, R. Aljumaily3, W..M. Korn4, J. Infante5, M. Patel6, K. Autio7, K. Papadopoulos8, A. Naing9, N.Y. Gabrail10, P. Munster11, J. Goldman1, N. Ratti12, P. Van Vlasselaer13, A. Hung12, M. Oft12, E. Garon14
  • 1Medicine, Hematology/oncology, UCLA - School of Medicine, 90095 - Los Angeles/US
  • 2Oncology, Winthrop University Hospital, Mineola/US
  • 3Cancer Center, OUHSC, Oklahoma City/US
  • 4Cancer Center, UCSF-Diller Cancer Research Building, Mount Zion, 94115 - San Francisco/US
  • 5Oncology, Sarah Cannon Research Institute-cancer centre, 37203 - Nashville/US
  • 6Oncology, Sarah Cannon Research Institute/Florida Cancer Specialists, Sarasota/US
  • 7Gu-immunotherapeutics, MSKCC, New York/US
  • 8Oncology, South Texas Accelerated Research Therapeutics (START), 78229 - San Antonio/US
  • 9Investigational Therapeutics, MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 10Cancer Center, Gabrail Cancer Center, Canton/US
  • 11Cancer Center, UCSF Helen Diller Family Comprehensive Cancer Center, 94115 - San Francisco/US
  • 12Clin Development, ARMO BioSciences, 94063 - Redwood City/US
  • 13Corp, ARMO BioSciences, 94063 - Redwood City/US
  • 14Medicine: Hem/onc, UCLA Hematology/Oncology Santa Monica, 90404 - Santa Monica/US

Abstract

Background

At therapeutic concentrations, PEGylated IL-10 (AM0010) stimulates the cytotoxicity, survival and proliferation of intratumoral antigen activated CD8+ T cells in pre-clinical cancer models and in patients. AM0010 activates antigen stimulated CD8 T cells while PD-1 inhibits them, providing a rationale for combining AM0010 with PD-1 inhibitors.

Methods

34 NSCLC pts received AM0010 (10-20ug/kg QD, SC) with pembrolizumab (2mg/kg, q3wk IV; n = 5) or nivolumab (3mg/kg, q2wk IV; n = 29). Pts had a median of 2 prior therapies. The median follow-up is 14.9 mo (range 5.6-30.3). Tumor responses were assessed by irRC. 20 patients were analyzed for PD-L1 expression (22C3). Immune responses were measured by analysis of serum cytokines (Luminex), activation of blood derived CD8 T cells (FACS) and peripheral T cell clonality (TCR sequencing). Tumor tissue was analyzed for tumor mutational burden by WES and mRNA expression of IO markers (Nanostring).

Results

AM0010 plus anti-PD-1 was well tolerated. All TrAEs were reversible and transient. G3/4 TrAEs included thrombocytopenia (8), anemia (7), fatigue (6), rash (4), pyrexia (2), hypertriglyceridemia (3) and pneumonitis (1). As of Sept 15, 2017, 27 pts had at least 1 tumor assessment. 10 pts (36.4%) had a partial response (PR) and 12 pts (44.4%) had stable disease (SD). Notably, of five patients with PD-L1 + ≥ 50% NSCLC, four had a PR, 1 had SD with 47% reduction of tumor burden.Table: 9PD

Preliminary response data stratified for PD-L1

NSCLC (n = 27)PD-L1 (22C3 IHC) (n = 20)IHC not available n = 6

Conclusions

AM0010 in combination with an anti-PD-1 is well-tolerated in advanced NSCLC pts. The improved efficacy regardless of PD-L1 status and the observed CD8 T cell activation is promising and encourages the continued study of AM0010 in combination with an anti-PD-1.

Clinical trial identification

NCT02009449

Legal entity responsible for the study

ARMO BioSciences

Funding

ARMO BioSciences

Disclosure

N. Ratti, A. Hung, M. Oft: Employee of ARMO BioSciences. P. Van Vlasselaer: Employee and stock owner of ARMO BioSciences. All other authors have declared no conflicts of interest.