Abstract 1083P
Background
Patients (pts) with advanced melanoma resistant to immune checkpoint inhibitors (ICI) may benefit from oncolytic viruses. ONCOS-102 (Ad5/3-D24-GM-CSF), a chimeric oncolytic adenovirus expressing human granulocyte-macrophage colony stimulating factor, has demonstrated innate and adaptive immune responses in solid tumors. This study assessed the safety, clinical and immune responses of sequential (Part 1) or combined (Part 2) ONCOS-102 and pembro for pts with advanced melanoma after prior PD-1 blockade.
Methods
Pts received 3 doses of ONCOS-102 on days 1, 4, and 8 followed by up to 8 doses of pembro q3 weeks (Part 1, N=9) or 4 doses of ONCOS-102 on days 1, 4, 8, 15 followed by up to 8 doses of ONCOS-102 plus pembro q3 weeks (Part 2, N=12). Biopsies were done at baseline, week 3 and 9. Primary objective was safety; secondary objectives included Objective Response Rate (RECIST 1.1) and immunologic changes in tumor and peripheral blood.
Results
Safety (n=21) and efficacy (n=20) were assessed. Treatment emergent AEs included pyrexia (10%), chills (8%), nausea and hypertension (4%). There were no dose limiting toxicities. Best overall response was 7/20 (35%) (Part 1: 3/8 (38%); Part 2: 4/12 (33%)). Non-injected lesions decreased in 4 of 20 pts. ONCOS-102 increased CD8+ T-cells in both injected and non-injected tumors as well as in plasma. CD8+/Treg ratio increased in tumors of responding pts from day 22 to day 64. Numerous immune-related genes (cytotoxicity, co-stimulatory molecules, checkpoints, TLR9 and T cell inflammation) were upregulated in ONCOS-102 treated tumors. Table: 1083P
Patient characteristics
| Parameters | Part 1 (n=8) | Part 2 (n=12) | Total (n=20) |
| Median age years (range) | 73 (40-87) | 72 (43-83) | 73 (40-87) |
| Sex (F/M) | 4/5 | 6/6 | 10/11 |
| AJCC stage III/IV | 6/2 | 5/7 | 11/9 |
| Median tumor burden, mm (range) | 37.5 (15-117) | 73.5 (11.8-174) | 55 (11.8-174) |
| Median time from last aPD1 failed treatment to study start, months (range) | 1.8 (0.9-24.5) | 1.9 (0.7-21.2) | 1.9 (0.7-24.4) |
Conclusions
Treatment with ONCOS-102 and pembrolizumab was well tolerated. Objective responses were seen in 35% of pts with PD-1 refractory melanoma, including in non-injected lesions. Immunologic changes in blood and tumor suggest ONCOS-102 may synergize with ICI.
Clinical trial identification
NCT03003676, 28/12/2016.
Editorial acknowledgement
Legal entity responsible for the study
Targovax ASA.
Funding
Targovax ASA.
Disclosure
A.N. Shoushtari: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Immunocore; Financial Interests, Personal, Royalties: UptoDate; Financial Interests, Institutional, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Institutional, Invited Speaker: Immunocore; Financial Interests, Institutional, Invited Speaker: Polaris; Financial Interests, Institutional, Invited Speaker: Xcovery; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Novartis; Non-Financial Interests, Member: ASCO. A.J. Olszanski: Financial Interests, Institutional, Principal Investigator: Targovax ASA; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Institutional, Principal Investigator: Alkermes; Financial Interests, Institutional, Principal Investigator: Astellas; Financial Interests, Institutional, Principal Investigator: Bristol-Myers Squibb; Financial Interests, Institutional, Principal Investigator: Checkmate Pharmaceuticals; Financial Interests, Institutional, Principal Investigator: Gan & Lee; Financial Interests, Institutional, Principal Investigator: Glyconex; Financial Interests, Institutional, Principal Investigator: Intensity Therapeutics; Financial Interests, Institutional, Principal Investigator: InstilBio; Financial Interests, Institutional, Principal Investigator: Kadmon; Financial Interests, Institutional, Principal Investigator: Kartos; Financial Interests, Institutional, Principal Investigator: OncoSec; Financial Interests, Institutional, Principal Investigator: Sound Biologics; Financial Interests, Institutional, Principal Investigator: SpringBank; Financial Interests, Institutional, Principal Investigator: Sumitomo Dainippon Pharma; Financial Interests, Institutional, Principal Investigator: Takeda. M. Nyakas: Financial Interests, Institutional, Principal Investigator: Targovax ASA; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Merck Scharpe & Dohme. T.J. Hornyak: Financial Interests, Institutional, Principal Investigator: Targovax ASA. J.D. Wolchok: Financial Interests, Personal, Advisory Board: Adaptive Biotech; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Apricity; Financial Interests, Personal, Advisory Board: Ascentage Pharma; Financial Interests, Personal, Advisory Board: Arsenal IO; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Beigene; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal and Institutional, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Chugai; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Dragonfly; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Elucida; Financial Interests, Personal, Advisory Board: F Star; Financial Interests, Personal, Advisory Board: Georgiamune; Financial Interests, Personal, Advisory Board: Idera; Financial Interests, Personal, Advisory Board: Imvaq; Financial Interests, Personal, Advisory Board: Kyowa Hakko Kirin; Financial Interests, Personal, Advisory Board: Linnaeus; Financial Interests, Personal, Advisory Board: Maverick Therapeutics; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Neon Therapeutics; Financial Interests, Personal, Advisory Board: Polynoma; Financial Interests, Personal, Advisory Board: Psioxus; Financial Interests, Personal, Advisory Board: Recepta; Financial Interests, Personal, Advisory Board: Takara Bio; Financial Interests, Personal, Advisory Board: Trieza; Financial Interests, Personal, Advisory Board: Truvax; Financial Interests, Personal, Advisory Board: Trishula; Financial Interests, Personal, Advisory Board: Sellas; Financial Interests, Personal, Advisory Board: Serametrix; Financial Interests, Personal, Advisory Board: Surface Oncology; Financial Interests, Personal, Advisory Board: Syndax; Financial Interests, Personal, Advisory Board: Syntalogic; Financial Interests, Personal, Advisory Board: Werewolf Therapeutics; Financial Interests, Institutional, Research Grant: Sephora; Financial Interests, Personal, Stocks/Shares: Tizona Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Adaptive Biotechnologies; Financial Interests, Personal, Stocks/Shares: Imvaq; Financial Interests, Personal, Stocks/Shares: Beigene; Financial Interests, Personal, Stocks/Shares: Linnaeus; Financial Interests, Personal, Stocks/Shares: Apricity; Financial Interests, Personal, Stocks/Shares: Arsenal IO; Financial Interests, Personal, Stocks/Shares: Georgiamune. V. Levitsky: Financial Interests, Personal, Full or part-time Employment: Targovax ASA. A. Møller: Financial Interests, Personal, Full or part-time Employment: Targovax ASA. L. Kuryk: Financial Interests, Personal, Full or part-time Employment: Targovax ASA. K. Risberg Handeland: Financial Interests, Personal, Full or part-time Employment: Targovax ASA. M. Jäderberg: Financial Interests, Personal, Full or part-time Employment: Targovax ASA.