Study of Radiotherapy Administered in Combination With Ipilimumab in Patients With Unresectable Stage III or Stage IV Advanced Malignant Melanoma

Summary

RATIONALE:Anti-melanoma activity of Ipilimumab both as a single therapy and in association with melanoma peptides has been shown as well as synergy between radiation therapy and anti-CTLA-A mAb in several tumor animal models for both local tumor control and distant effects.Radiotherapy increases tumor immunogenicity in several preclinical models by increasing MHC molecules expression and is able to induce significant tumor reduction in around 30% of cases. Thus, combining radiotherapy and administration of ipilimumab could elicit systemic antitumor response. Radiation therapy will expose tumor-associated antigens (TAA) and facilitate antigen presentation, and further blockade of CTLA-4 could amplify the immune antitumor response. In this therapeutical model, the use of the own patient tumor as a source of tumor antigens (in opposition with other vaccination protocols, where TAA are exogenic) is particularly adapted. PURPOSE: This Phase I trial determines the side effects and best dose of radiation therapy administered in combination with ipilimumab.

Timeline

Start

2011-03

Primary completion

2015-11

Completion

2016-03

Outcome

Outcome not reported

Stopped: “New compounds available in the indication (nivolumab/pembrolizumab), toxicity of ipilimumab”

Publications

• Boutros C, Chaput-Gras N, Lanoy E, Larive A, Mateus C, Routier E, Sun R, Tao YG, Massard C, Bahleda R, Schwob D, Ibrahim N, Khoury Abboud RM, Caramella C, Lancia A, Cassard L, Roy S, Soria JC, Robert C, Deutsch E. Dose escalation phase 1 study of radiotherapy in combination with anti-cytotoxic-T-lymphocyte-associated antigen 4 monoclonal antibody ipilimumab in patients with metastatic melanoma. J Immunother Cancer. 2020 Aug;8(2):e000627. doi: 10.1136/jitc-2020-000627.

Drugs

Indications