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.
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.
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.
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
Legal entity responsible for the study
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.