Overall survival of PEGylated human IL-10 (AM0010) with 5-FU/LV and oxaliplatin (FOLFOX) in metastatic pancreatic adenocarcinoma (PDAC).

Abstract

374 Background: The therapeutic options for 2nd line therapy PDAC remain unsatisfying with 5-FU/LV plus oxaliplatin or nal-irinotecan resulting in a mOS of 5-6 mo. PDAC has been largely refractory to immune-oncology approaches and CD8 T cells are rare in most PDAC. AM0010 stimulates survival, expansion and cytotoxicity of intratumoral CD8+ T cells. Immune activation, durable stable disease and a 1yr survival of 22.5% was seen in salvage PDAC patients (pts) receiving AM0010 alone. AM0010 has synergistic anti-tumor activity with 5-FU/LV or oxaliplatin in preclinical models. Here we report on the safety, efficacy and overall survival of AM0010 + FOLFOX as 2nd and later line treatment in PDAC. Methods: PDAC progressing on a median of 2 prior therapies (range 1-5) were treated with AM0010 (5ug/kg SQ, qd) + FOLFOX (n = 21). The safety population (n = 25) included also 4 pts with prior oxaliplatin / 5-FU. The survival population included patients without prior platinum containing regimen. Tumor responses were assessed with irRC. Biomarkers evaluated the activation and clonality of peripheral T cells. Archival tumor tissues were evaluated for tumor infiltration by CD8 T cells, by whole exome sequencing and mRNA analysis. Results: AM0010 + FOLFOX, was generally well tolerated. G3/4 TrAEs included thrombocytopenia (52%), anemia (44%), neutropenia (36%) and fatigue (12%). Most cytopenias had a short duration, reaching retreatment criteria within 2-5 days after dose interruption. Dosing AM0010 for 5 days followed by a 2 days dose holiday avoided G3/4 cytopenias. As of 08/11/2017, 2 patients have remained on treatment for > 1 year. Of 19 evaluable pts, 2 had an irCR, 1 had irPR with 100% reduction in tumor burden, ORR is 15.8%, DCR is 78.9%. With median follow-up of 19.2 months (range 13.4-24.1), mPFS was 3.5 mo, mOS was 10.2 mo and 1-year survival was 43%. Transcriptional profiling and CD8 T cells in the archival tumor tissue may identify patients with longer OS. Conclusions: AM0010 in combination with FOLFOX is well tolerated in patients with metastatic PDAC. Immune activation, mOS and 1 year survival are encouraging in this advanced PDAC population. This regimen is currently being studied in a phase 3 trial Clinical trial information: NCT02009449.