724O - EO2401 (E) peptide immunotherapy + nivolumab (N) in adrenocortical carcinoma (ACC) and metastatic pheochromocytoma/paraganglioma (MPP): EOADR1-19/SPENCER

Background

E expands memory T cells recognizing proteins from gut bacteria, which cross-react with tumor associated antigens. E contains 3 CD8 HLA-A2 epitopes with mimicry to IL13Rα2, BIRC5, and FOXM1, and the CD4 epitope UCP2.

Methods

Patients (pt) received E (300 μg/peptide, q2w x4 then q4w) with N (240 mg q2w x3 then 480 mg q4w) in cohorts: C1 (safety lead-in); ACC in C2a and C2b with 2nd/3rd and 1st -line systemic therapy metastatic disease, respectively; MPP in C3a after prior and in C3b as 1st -line systemic therapy. Based on C2a results, a randomized extension, RND-C2a, was initiated (65 pt, 4:1:1, E/N vs E vs N).

Results

Recruitment to C1, C2a and C2b is completed, MPP cohorts and RND-C2a are recruiting (Table). EN was well tolerated in C1 (3 pt) and thereafter, with E associated events limited to local skin events (50% of pt Gr 1/2, 4% Gr 3) and N-tox in expected range. Two main groups for C2a efficacy, one with no benefit (10 pt PD/death week 8). No impact of TMB, MSI-status, PD-L1 expression, cytokines, chemokines, or hormones on efficacy. Post-hoc analyses identified predictors of lack of efficacy (no mitotane, ECOG > 1, ACC 1st diagnosis ≤9 months(mo), lesion size >125 mm, >3 organs involved, lymphopenia >grade 1); C2-post hoc group was created applying these factors.

EN induced specific T cell expansion in 91% of tested pt (67% of all treated pt); durations up to 19 mo. Strength of immune response correlated with progression-free survival.

Table: 724O

DC disease control; SD stable disease; PR partial response; CR complete response; OR objective response; NR not reached; ∗median (range) in months; ^ˆlocal therapies allowed for symptoms; “too early, futility assessment at n⁓19.

Conclusions

EO2401/N was well tolerated generating durable immune responses correlating with efficacy. Based on the greater efficacy in C2-post hoc group a randomized extension is currently recruiting.

Clinical trial identification

NCT04187404.

Editorial acknowledgement

Legal entity responsible for the study

Enterome.

Funding

Enterome.

Disclosure

E. Baudin: Financial Interests, Personal, Other, Project lead and principal investigator: Ipsen; Financial Interests, Personal, Advisory Board: Novartis-AAA; Financial Interests, Institutional, Research Grant: Novartis, HRA; Non-Financial Interests, Principal Investigator: Enterome; Non-Financial Interests, Leadership Role, French network of endocrine and neuroendocrine tumors: Endocan Network. J. Capdevila Castillon: Financial Interests, Personal, Invited Speaker: Novartis, Novartis, Pfizer, Ipsen, Exelixis, Bayer, Eisai, Advanced Accelerator Applications, Amgen, Sanofi, Lilly, Merck Serono; Financial Interests, Personal, Advisory Board: Pfizer, Ipsen, Exelixis, Bayer, Eisai, Advanced Accelerator Applications, Amgen, Sanofi, Lilly, Merck Serono, Esteve, ITM; Financial Interests, Personal, Research Grant: Novartis, Bayer, Pfizer, AstraZeneca, Advanced Accelerator Applications, Eisai. M. Fassnacht: Financial Interests, Institutional, Local PI, Clinical trial on adrenocortical carcinoma and malignant pheochromocytoma: Enterome Bioscience; Financial Interests, Institutional, Local PI, Clinical trial in Cushing's syndrome: HRA Pharma, Corcept; Non-Financial Interests, Leadership Role: European Network for the Study of Adrenal Tumor; Non-Financial Interests, Member of Board of Directors: European Society of Endocrinology; Non-Financial Interests, Member: European Network for the Study of Adrenal Tumors; Other, Data safety board for a clinical trail (compensation is paid to the Institution): Bayer Pharma. C. de la Fouchardiere: Financial Interests, Personal, Advisory Board: Merck, Roche, Lilly, Bayer, Amgen, MSD, Servier, Pierre Fabre Oncologie, Bristol Myers Squibb, Incyte, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Ipsen, Eisai, Servier, MSD, Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: Pierre Fabre Oncologie, Servier; Non-Financial Interests, Principal Investigator: Amgen, Daiichi Sankyo, MSD. M. Kroiss: Financial Interests, Institutional, Other, Research support: Ipsen, Lilly; Financial Interests, Institutional, Advisory Board: Bayer, Lilly; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Institutional, Other, Travel support: Catalym; Non-Financial Interests, Principal Investigator: MSD; Non-Financial Interests, Institutional, Other, MTA: Corcept; Non-Financial Interests, Leadership Role: European Network for the Study of Adrenal Tumours; Non-Financial Interests, Member: Deutsche Krebsgesellschaft. K.G. Daugaard: Financial Interests, Personal, Advisory Board, Prostate cancer: Janssen; Financial Interests, Personal, Advisory Board, Prostate Cancer: Astellas, Bayer, MSD; Financial Interests, Personal, Advisory Board, Anticoagulation therapy: BMS; Financial Interests, Personal, Advisory Board: AA; Financial Interests, Institutional, Coordinating PI: BMS, Roche, MSD. L. Lamartina: Financial Interests, Personal, Advisory Board: Eisai, Bayer, Ipsen; Financial Interests, Personal, Invited Speaker: Lilly, Ipsen; Financial Interests, Institutional, Local PI: Exelixis, isai, Sanofi, Bayer. J. Paillarse, L. Aubergeon, J. Fagerberg, L. Chêne: Financial Interests, Personal, Full or part-time Employment: Enterome. A. Berruti: Financial Interests, Personal, Advisory Board: Amgen, Astellas, Janssen, Ipsen; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker, Public speaking in international webinar: HRA; Financial Interests, Institutional, Funding: Astellas, Janssen; Non-Financial Interests, Institutional, Product Samples: Sanofi, Novartis. All other authors have declared no conflicts of interest.