Phase I/II Trial of Dinutuximab Beta in Combination With Irinotecan and Rapamycin in Pediatric, Adolescents and Adult Patients With Relapsed/Refractory Bone Tumors. (BONE DINIRRA)

Osteosarcomas, like other primitive bone tumors, remain hard-to-treat malignancies, especially after failure of first-line treatments. Multiple mechanisms are initiating or rendering bone tumor cells resistant to the chemotherapies leading to the drastic reduction of treatment possibilities in case of relapses. Among the list of extra-tumoral mechanisms enabling this cancer cell resistance, hypoxia and tumor-associated macrophage modulation seem to be in the top ranks. Based on that, we generated by the past tumor data where the study of hypoxic biomarkers' expressions and the presence of protumoral macrophages were influencing the prognosis of osteosarcoma patients. In fact, the association of HIF1 hyperexpression and a high number of M2 phenotype macrophages (e.g., protumoral cells) were predictive markers of the worst outcome. We recently redone this translational approach in other bone tumors like Ewing sarcomas (EWS) showing the same prognostic tendency. Furthermore, a past pediatric phase I trial, named RAPIRI, targeting both mTor and HIF1, with combination of Sirolimus and…

• Phase 1: Determination of the maximum tolerated dose (MTD) of Dinutuximab beta, given in combination with iv. Irinotecan (day 1 and day 15) and daily oral Sirolimus
• Phase 2:

1. Study completion expected

   Feb 2033

2. Primary completion expected

   Feb 2031

3. Expected to start

   Oct 2026

4. Registered

   1 Oct 2026