Phase I-II trial of sunitinib plus nivolumab after standard treatment in advanced soft tissue and bone sarcomas

Sarcomas are rare, life-threatening, malignant tumors affecting soft, visceral, and bone tissues. Due to their high heterogeneity (more than 60 subtypes), many sarcomas lack effective therapies. Incidence is 50-60 new cases/year per million. 20% are metastatic at diagnosis and 40% of localized cases will develop metastases. For locally advanced or metastatic disease, few curative options might be offered. In metastatic setting, complete responses to chemotherapy are very rare and median of survival is around 1 year. Most cytotoxic chemotherapies have reached a ceiling in efficacy. Median PFS in first line is 3.5-5 months. Few new drugs have been approved in the last decade offering some survival benefit. Median PFS for most second line drugs is around 2.5 months. New treatments are urgently needed.
IMMUNOSARC is a phase II, single-arm, open-label, international clinical trial exploring the synergistic efficacy of the anti-PD-1 (nivolumab) plus antiangiogenic agent (sunitinib) combination in advanced/metastatic soft tissue and bone sarcomas. Tumor formalin-fixed paraffin-embedded samples at baseline and at week 13 were collected prospectively during the IMMUNOSARC phase II clinical trial. This translational study seeks to develop new immunological strategies for the treatment of sarcomas, by investigating the impact of immune target drug nivolumab and the role of immune modulation due to sunitinib, along with their interaction. Genomic analyses (direct transcriptomics with HTG Molecular technology) and protein expression tests (Multiplex procarta panel and co-localization by immunohistochemistry/ immunofluorescence-based assays) will help describe new potential predictive or other prognostic biomarkers in patients treated with immunotherapy.

This prospective project, led by Javier Martin-Broto, is part of a positive clinical trial and aims to increase the knowledge in sarcomas immune modulation, as a groundbreaking approach to develop or improve sarcoma therapy. The in-depth study of sarcoma immunotherapy offers a good chance to discover key immunologic insights that may have wider application in cancer therapeutics as a whole.