94TiP - Combination therapy with Nivolumab and PD-L1/IDO peptide vaccine to patients with metastatic melanoma. A clinical trial in progress. (94TiP)

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Cancer Immunology and Immunotherapy
Translational Research
Presenter Julie Kjeldsen
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors J.W. Kjeldsen1, M.H. Andersen2, I. Svane1
  • 1Department Of Oncology, Herlev and Gentofte Hospital, 2730 - Herlev/DK
  • 2Department Of Hematology, Center for Cancer Immune Therapy, 2730 - Herlev/DK

Abstract

Background

Huge advances have been made in the treatment of metastatic melanoma (MM); especially immunotherapy is showing impressive results. Combination of Ipilimumab and Nivolumab is to date the most effective treatment strategy, but over 50% of the patients experience grade 3/4 adverse events. New effective combinations with less toxicity are strongly needed. It is known that cancer cells induce a state of tolerance against the immune system. Two well-known mechanisms are brought through overexpression of PD-L1 and IDO on the tumor cells, which inhibits activation of cytotoxic T-cells. We have identified spontaneous T-cell reactivity against PD-L1 and IDO in the tumor microenvironment and in the peripheral blood of patients with MM and healthy donors. Both IDO and PD-L1 reactive CD8 T-cells are cytotoxic and can kill cancer cells and immune regulatory cells in vitro. Thus boosting specific T-cells that recognize immune regulatory proteins such as IDO and PD-L1 may directly modulate immune regulation. Due to distinct mechanisms of action, the combination of treatment with a monoclonal antibody targeting PD-1 and a vaccine with peptides against PD-L1 and IDO may have a synergistic effect. We recently reported a phase I trial where the IDO peptide was tested in 15 patients with MM in combination with Ipilimumab leading to induction of immunity without increased toxicity. The PD-L1 peptide is currently being tested in patients with multiple myeloma, so far without severe toxicity.

Trial design

A two-step clinical phase I/II trial design is used. 6 patients with MM will be included in a pilot study to test feasibility and tolerability. If the treatment is feasible 24 patients will further be included. The objectives are to describe anti-tumor immune responses in both blood as well as tumor tissue samples and objective responses using RECIST 1.1. Patients are treated with Nivolumab, involving outpatient IV infusions biweekly as long as there is clinical benefit. The PD-L1/IDO (IO102/IO103) peptide vaccine is given from start of Nivolumab and biweekly for the first 6 vaccines and thereafter every fourth week up to 1 year. Patients will be followed with clinical controls and diagnostic imaging every 12 weeks.

Clinical trial identification

NCT03047928

Legal entity responsible for the study

Inge Marie Svane

Funding

IO Biotech

Disclosure

All authors have declared no conflicts of interest.