EO was created to stimulate memory T cells that cross-react with antigens linked with tumor associated antigens (TAAs). The HLA-A2 restricted peptides (IL13Rα2, BIRC5, and FOXM1) mimicked by TAAs and elevated in ACC/MPP and CD4 peptide UCP2 are included in EO.
Nivolumab (N) and EO were shown to be safe in Cohort (C) 1; C2a/3a patients underwent analysis. Patients who had had prior systemic treatment for advanced illness and had non-resectable ACC (C2) and MPP (C3) with (C2a/3a) or without (C2b/3b) received EO (300 μg/peptide, Q2 weeks (w) x4 then Q4 w) + N (240 mg/dose x3, then 480 mg/dose, after EO) = EN.
Entered with 33 points from ACC (C2a 26, C2b 7) and 13 points from MPP (C3a 9, C3b 4). Except for local administration site responses to EO (35% of patients; grades 1-3), EN was well tolerated and had a safety profile similar to that of N mono. Objective response rate (ORR) was 12%, disease control rate (DCR; ORR + SD) was 36%, and median progression-free survival (mPFS) was 1.9 mo (12% ongoing 38-50 w) in ACC (n=33, median follow-up [mFU] 10.5 months [mo]). There was no evidence that past treatment affected ORR or PFS. C2a 11.3 mo (46% alive 35-76 w) and C2b NA (86% alive 29-49 w) are the median survival rates (mOS). With respect to MPP (n=13, mFU 9.6 mo), ORR was 7%, DCR was 77%, mPFS was 4.7 mo (38% continued 9-40 w), and mOS was 11.4 mo (62% alive 14-57 w). There is currently no effect from past treatment. The results of CD8 T cell ELISPOT tests against the EO peptides (19/20 points) and cross-reactivity with the intended TAAs (15/16 evaluable points) were both positive. Maximum immune response levels and clinical results are correlated. Clinical variables (no mitotane, ECOG > 1, ACC 1st diagnosis ≤9 mo, max lesion size >125 mm, >3 organs implicated, decreased lymphocytes >grade 1) were discovered by post-hoc studies, which led to the exclusion of the majority of patients in C2a without benefit. ORR was 29%, DCR was 64%, mPFS was 3.8 mo, and mOS was 13.0 mo in the post-hoc favorably chosen group (n=14, mFU 12.4 mo). Patients that had a good prognosis had few mutations and little PDL1 expression. Clinical benefits and cytokines/chemokines did not correlate.
The immunological responses triggered by EO2401 were well tolerated and correlated with its effectiveness. Clinical criteria were used to define the efficacy in the ACC group post hoc; randomized research was beginning.