744P - Overall Survival and Immunologic Responses in Metastatic Pancreatic Adenocarcinoma (PDAC) on PEGylated Human IL-10 (AM0010) with 5-FU/LV and Oxalip...

Date 09 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cytotoxic agents
Immunotherapy
Pancreatic Cancer
Gastrointestinal Cancers
Therapy
Biological therapy
Presenter J. Randy Hecht
Citation Annals of Oncology (2017) 28 (suppl_5): v209-v268. 10.1093/annonc/mdx369
Authors J..R. Hecht1, A. Naing2, G. Falchook3, M.R. Patel4, J.R. Infante5, R. Aljumaily6, D.J. Wong7, K. Autio8, Z.A. Wainberg1, M. Javle2, J.C. Bendell9, S. Pant10, A. Hung11, P. Van Vlasselaer11, G. Brown11, M. Oft11, K. Papadopoulos12
  • 1Medicine, UCLA, 90095 - Los Angeles/US
  • 2Medical Oncology, MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 3Healthone, Sarah Cannon Research Institute, Denver/US
  • 4Oncology, Sarah Cannon Research Institute (Nashville, TN); Florida Cancer Specialists & Research Institute, Sarasota/US
  • 5Medical Oncology, Sarah Cannon Research Institute/Tennessee Oncology, 37203 - Nashville/US
  • 6Hematology/oncology, Oklahoma University Medical Centre, Oklahoma City/US
  • 7Department Of Medicine, University of California, Los Angeles, 90024 - Los Angeles/US
  • 8Genitourinary Oncology, MSKCC, 10065 - New York/US
  • 9Medical Oncology, Sarah Cannon Research Institute and Tennessee Oncology, 37203 - Nashville/US
  • 10Oncology, College of Pharmacy, OUHSC, 73117 - Oklahoma City/US
  • 11Clinical Development, ARMO BioSciences, 94063 - Redwood City/US
  • 12Oncology, South Texas Accelerated Research Therapeutics (START), 78229 - San Antonio/US

Abstract

Background

Median overall survival on 2nd line therapy of PDAC with 5-FU/LV plus oxaliplatin or nal-irinotecan is ∼ 5-6 m. PDAC is refractory to immune therapies and mutational burden is relatively low and tumor infiltrating CD8+ T cells are rare. AM0010 stimulates survival, expansion and cytotoxicity of intratumoral CD8+ T cells and induced immune activation, durable stable disease and a 1yr survival of 22.5% in salvage PDAC pts. AM0010 has synergistic immune and anti-tumor activity with platinums and 5-FU in preclinical cancer models.

Methods

This phase 1b clinical study studied the safety and efficacy of AM0010 +FOLFOX as ≥ 2nd line treatment of PDAC. Pts who progressed on a median of 2 prior therapies (range 1-3) were treated with AM0010 (5ug/kg SQ, qd) + FOLFOX (n = 21). The safety population (n = 25) included four additional pts with prior FOLFOX. Tumor responses were assessed using irRC. Serum cytokines, activation of blood derived T cells and peripheral T cell clonality were analyzed. Pre-existing tumor infiltrating CD8 T cells were quantified by IHC.

Results

AM0010 + FOLFOX was generally well tolerated. G3/4 TrAEs included thrombocytopenia (52%), anemia (40%) and neutropenia (36%). Most cytopenias were transient and met retreatment criteria within 2-5 days. A modified AM0010 dose schedule of 5 days on, 2 days off avoided G3/4 cytopenias while retaining the immune stimulation. As of 05/1/2017, 2 pts have remained on treatment for > 72 weeks. 19 pts had tumor assessment following irRC (2 CR, 1 PR, 11 SD). The ORR and DCR were 15.8% and 74%. With a median follow-up of 14.2 m (range 6.8-18.9), 10 patients were alive (48%), mPFS and mOS were 3.5 and 10.2 m. Treatment induced a sustained cytokine increase in the serum and an expansion of novel T cell clones in the blood. This and a higher number of intra-tumoral CD8 T cells correlated with increased OS.

Conclusions

The combination of AM0010 with FOLFOX is well tolerated in patients with metastatic PDAC. This regimen induced sustained immune activation including the expansion of oligoclonal T cells. The prolonged tumor responses and OS are encouraging in this advanced population. This regimen is being studied in a phase 3 trial.

Clinical trial identification

NCT02009449

Legal entity responsible for the study

Armo BioSciences

Funding

ARMO BioSciences

Disclosure

A. Hung, G. Brown: Employee of ARMO BioSciences. P. Van Vlasselaer: Stock, leadership, employee of ARMO BioSciences. M. Oft: Employee of ARMO BioSciences. All other authors have declared no conflicts of interest.