2MO - EO2401 (EO) therapeutic vaccine for patients (pts) with adrenocortical carcinoma (ACC) and malignant pheochromocytoma/paraganglioma (MPP): Phase I/II SPENCER study

Background

EO was designed to activate memory T cells cross-reacting with tumor associated antigens (TAAs). EO includes microbial-derived synthetically produced HLA-A2 restricted peptides with mimicry to TAAs (IL13Rα2, BIRC5 and FOXM1) upregulated in ACC/MPP and CD4 peptide UCP2.

Methods

Cohort (C) 1 established safety of EO + nivolumab (N); pts analyzed in C2a/3a. Pts with non-resectable ACC (C2) and MPP (C3), with (C2a/3a), or without (C2b/3b), prior systemic therapy for advanced disease received EO (300 μg/peptide, Q2 weeks (w) x4 then Q4 w) + N (240mg/dose x3, then 480mg/dose, following EO) = EN. NCT04187404.

Results

33 pts with ACC (C2a 26, C2b 7), 13 pts with MPP (C3a 9, C3b 4) started EN. EN well tolerated and safety profile consistent with N mono except for local administration site reactions after EO (35% of pts; grades 1-3). In ACC (n=33, median follow-up [mFU] 10.5 months [mo]), objective response rate (ORR) 12%, disease control rate (DCR; ORR + SD) 36%, median progression-free survival (mPFS) 1.9 mo (12% ongoing 38-50 w). No influence of prior therapy on ORR/PFS observed. Median survival (mOS) C2a 11.3 mo (46% alive 35-76 w) and C2b NA (86% alive 29-49 w). In MPP (n=13, mFU 9.6 mo), ORR 7%, DCR 77%, mPFS 4.7 mo (38% ongoing 9-40 w) and mOS 11.4 mo (62% alive 14-57 w). Currently no influence of prior therapy. CD8 T cell ELISPOT responses against the EO peptides (19/20 pts) and cross-reactivity with targeted TAAs (15/16 evaluable pts) shown. Max level of immune response correlate with clinical outcome. Post-hoc analyses identified clinical factors (no mitotane, ECOG > 1, ACC 1st diagnosis ≤9 mo, max lesion size >125 mm, >3 organs involved, reduced lymphocytes >grade 1) excluding majority of pts in C2a without benefit. In post-hoc favorably selected group (n=14, mFU 12.4 mo) ORR 29%, DCR 64%, mPFS 3.8 mo and mOS 13.0 mo. Pts with favorable outcome had low mutational burden/PDL1 expression. Cytokines/chemokines did not correlate with clinical benefit.

Conclusions

EO2401 was well tolerated and generated immune responses correlating with efficacy. Efficacy seen in ACC group defined post-hoc by clinical parameters; a randomized study is starting. Expansion of MPP group ongoing, update will be presented.

Clinical trial identification

NCT04187404.

Editorial acknowledgement

Legal entity responsible for the study

Enterome.

Funding

Enterome.

Disclosure

E. Baudin: Financial Interests, Institutional, Advisory Board, Advisory board and principal investigator: Novartis; Financial Interests, Institutional, Advisory Board: HRA, Hutchinson Pharma; Financial Interests, Personal, Other, Project lead and principal investigator: Ipsen; Financial Interests, Institutional, Other: Pfizer; Financial Interests, Personal, Advisory Board: Novartis - AAA; Financial Interests, Institutional, Research Grant: Novartis, HRA, Pfizer; Non-Financial Interests, Principal Investigator: Enterome; Non-Financial Interests, Advisory Role: Hutchinson Pharma; Non-Financial Interests, Leadership Role: Endocan Network. S. Grisanti: Financial Interests, Personal, Advisory Role: Boehringer-Ingelheim, BMS Foundation, Sanofi-Aventis. M. Fassnacht: Financial Interests, Institutional, Invited Speaker, Clinical trial on adrenocortical carcinoma and malignant pheochromocytoma: Enterome Bioscience; Financial Interests, Institutional, Invited Speaker, Clinical trial in Cushing's syndrome: HRA Pharma, Corcept; Non-Financial Interests, Leadership Role: European Network for the Study of Adrenal Tumor; Data safety board for a clinical trial (compensation is paid to the Institution): Bayer Pharma. C.W. Menke-van der Houven van Oordt: Financial Interests, Institutional, Research Grant: BMS/Celgene, Pfizer, Cristal Therapeutics; Financial Interests, Institutional, Advisory Role: Novartis, Pfizer, Daiichi DSankyo/AstraZeneca. C. de la Fouchardiere: Financial Interests, Personal, Advisory Role: Lilly, Bayer, BMS, Amgen, Servier, Roche, Pierre Fabre, Incyte, Eisai, MSD Oncology, Ipsen; Financial Interests, Personal, Speaker’s Bureau: Ipsen; Financial Interests, Personal, Other, Travel, accomodation, expenses: Roche, Celgene, Amgen, BMS, Servier; Financial Interests, Personal, Other: Incyte, MSD; Financial Interests, Personal, Other, Honoraria: Merck Serono, Roche; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Pierre Fabre, Servier. V. Subbiah: Financial Interests, Personal, Advisory Role: MedImmune, Helsinn Therapeutics, Loxo, R-Pharm, QED Therapeutics; Financial Interests, Personal, Other, Travel, accomodation, expenses: PharmaMar, Bayer, Novartis, Helsinn Therapeutics; Financial Interests, Personal, Other: Medscape; Financial Interests, Institutional, Research Grant: Novartis, GSK, NanoCarrier, Northwest Biotherapeutics, Genentech/Roche, Berg, Bayer, Incyte, Fujifilm, PharmaMar, D3 ONcology Solutions, Pfizer, Amgen, AbbVie, Multivir, Blueprint Medicines, Loxo, Vegenics, Takeda, Alfasigma, Agenesys, Idera, Boston Biomedicall, Inhibrx, Exelixis, Amgen, Turning Point Therapeutics. C. Jimenez: Financial Interests, Personal, Other, Honoraria: MSD, Pfizer; Financial Interests, Personal, Advisory Role: MSD, Pfizer, Progenics, Lantheus, HRA Pharma; Financial Interests, Personal, Research Grant: MSD, Exelixis, Progenics, Lantheus. J. Capdevila Castillon: Financial Interests, Personal, Advisory Role: Amgen, Bayer, AAA, AstraZeneca, Eisai, Exelixis, Ipsen, ITM, Lilly, Sanofi, Merck, Novartis, Pfizer; Financial Interests, Personal, Speaker’s Bureau: Amgen, Bayer, AAA, AstraZeneca, Eisai, Exelixis, ITM, Lilly, Sanofi, Merck, Novaris, Pfizer; Financial Interests, Personal, Invited Speaker: Ipsen. D. Granberg: Financial Interests, Institutional, Research Grant: Enterome, MSD. K.G. Daugaard: Financial Interests, Personal, Advisory Role: Bayer Pharma, Astellas, MSD, Janssen; Financial Interests, Grant: Lilly, MSD, Janssen, BMS. M. Kroiss: Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Advisory Role: Loxo Oncology, Lilly, Ipsen, Bayer , Eisai, Ipsen; Financial Interests, Personal, R esearch Grant: Enterome, Lilly, Loxo Oncology; Financial Interests, Personal, Other, Travel, accomodation expenses: Lilly. O. Kimpel: Financial Interests, Personal, Other, Honoraria: HRA Pharma. L. Lamartina: Financial Interests, Personal, Other, Honoraria: Eisai; Financial Interests, Personal, Advisory Role: Bayer, Eisai, Ipsen; Financial Interests, Personal, Other, Travel, accomodatioon, expenses: AAA (Novartis). J. Hadoux: Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Advisory Role: Ipsen, AAA, Roche, PharmaMar, Lilly. J. Paillarse: Financial Interests, Personal, Member, employee and shareholder: Enterome. L. Chêne: Financial Interests, Personal, Leadership Role: Enterome. J. Fagerberg: Financial Interests, Personal, Leadership Role: Enterome. A. Berruti: Financial Interests, Personal, Advisory Role: Janssen-Cilag, Astellas Pharma, Amgen; Financial Interests, Personal, Speaker’s Bureau: Janssen-Cilag, Astellas Pharma; Financial Interests, Institutional, Research Grant: Janssen-Cilag, Astellas Pharma; Financial Interests, Personal, Other, Travel, Accomodation expenses: Janssen-Cilag, Sanofi. All other authors have declared no conflicts of interest.