Hospitals, industry, and associations join forces against rare cancers with the IMMUNORARE5 program
For 15 years, immunotherapy has been transforming the treatment of common cancers, but the lack of data for rare cancers limits access to these advances, creating healthcare inequalities. The IMMUNORARE 5 program, coordinated by the Hospices Civils de Lyon and conducted in 15 national centers, aims to address this.
A dual immunotherapy against rare cancers
The IMMUNORARE 5 program aims to evaluate the efficacy and tolerability of a dual immunotherapy combining domvanalimab and zimberelimab in patients with five types of rare cancers, for whom therapeutic options remain limited after the failure of first-line treatment.
The five rare cancers concerned are:
- peritoneal mesothelioma, treated with chemotherapy when complete surgery is no longer possible,
- gestational trophoblastic disease, resistant to polychemotherapy,
- aggressive forms of thymic cancer (type B3 or carcinoma), non-responsive to at least one line of chemotherapy,
- anaplastic thyroid cancer, uncontrolled by radiochemotherapy or targeted anti-BRAF therapy according to mutational status,
- neuroendocrine tumors progressing despite oxaliplatin-based treatment.
This multicenter study, coordinated by the Hospices Civils de Lyon (HCL) in fifteen French centers, will include approximately 130 patients, and aims, in the event of positive results, to promote wider and rapid access to this new dual immunotherapy for people with these rare cancers.
Biomarkers to guide immunotherapy
IMMUNORARE 5 plans to collect tumor, blood, saliva, and stool samples to identify biomarkers that can predict response or non-response after six months of treatment with the domvanalimab/zimberelimab dual immunotherapy in the five rare cancers under study. All data collected across the fifteen partner centers is centralized in a large computerized registry, the "electronic case report form," and analyzed directly at the HCL (Hospices Civils de Lyon).
The evaluation of therapeutic efficacy will vary depending on the pathology. For example, for peritoneal mesothelioma, the trial will be considered positive if more than 60% of patients show no clinical or radiological worsening. For gestational trophoblastic disease, it will be positive if more than 60% of patients normalize their hCG levels. For anaplastic thyroid cancer, the chosen criterion is survival greater than 50% after six months of treatment. Depending on the results and in the event of success, the partner entities hope to unite pharmaceutical industry players and the scientific community in the cause of rare cancers, in order to expand access to treatment and reduce inequalities in patient care.
Furthermore, the indirect benefits of the program aim to strengthen France's visibility and attractiveness in the implementation of national drug development programs and in biomarker research. As part of the Ten-Year Cancer Control Plan (priority areas 3 and 4), IMMUNORARE5 thus contributes to maintaining French leadership in rare cancer expertise.
A major multi-partner program
The IMMUNORARE 5 program relies on broad cooperation between teams and partners with complementary expertise.
Among the fifteen partner French medical centers are the Gustave Roussy Institute, AP-HP Tenon Hospital, the Curie Institute, the Lille University Hospital, the Bergonié Institute in Bordeaux, the IUCT-Oncopole Toulouse, the Western Cancer Institute (ICO), AP-HM Timone Hospital, the Paoli-Calmettes Institute Marseille, the Eugène-Marquis Center Rennes, the Regional Cancer Institute of Montpellier, and the Strasbourg University Hospital. A dedicated coordination team, composed of project managers, clinical research associates, pharmacists, data managers, methodologists, biostatisticians, and financial managers, ensures the smooth running of the trial across the fifteen centers and oversees the complete data management.
The national reference centers for rare cancers, certified by the French National Cancer Institute (INCa) or the European Reference Networks for Rare Diseases (ERN), are also fully associated.
The HCL teams, experts in the targeted pathologies, have solid experience in patient management and rely on their networks to ensure equitable access to the program across the entire country. They also benefit from the support of EPSILYON, a structure specialized in complex early trials, which manages the entire process: development of the scientific rationale, search for funding, writing of protocols, regulatory procedures, therapeutic follow-up, and data collection and analysis.
Funding for the trial and the supply of the dual immunotherapy are provided through the partnership with the pharmaceutical laboratory Gilead. The program also benefits from the support of patient associations and charitable organizations, such as the Ligue contre le cancer and Rotary International, which contribute to the funding of complementary research projects.
The strength of the public-private alliance
With IMMUNORARE 5, HCL once again demonstrates the potential and value of public-private collaborations, particularly through supported academic clinical trials. The pharmaceutical industry finances and provides the medicines, entrusting expert academic teams with the design and conduct of specialized studies. The latter can thus conduct clinical research independently, centered on patients' needs, while fulfilling their public service mission.
This multi-partner national program is an example of bringing together high-level complementary expertise around a common ambition: to make therapeutic innovations accessible to all patients, without exception!
Sources: © La Gazette du Laboratoire - J S.Lopes
