(P 408) OSTEOMYC: A PHASE 2 PILOT STUDY TO EVALIATE THE SAFETY AND THE ANTITUMOR ACTIVITY OF THE MYC INHIBITOR OMO-103 ADMINISTERED INTRAVENOUSLY IN PATIENTS WITH ADVANCED HIGH GRADE OSTEOSARCOMA

Objective: Osteosarcoma is the most common primary malignant bone tumour in teenagers and young adults, although it has a second peak of incidence in older patients. The initial treatment of high-grade osteosarcoma is multimodal. For patients with recurrent disease or progressing after first line chemotherapy, the prognosis remains poor with few systemic options.
The pathogenesis of osteosarcoma involves complex molecular mechanisms, with dysregulation of various oncogenes and tumour suppressor genes. Among these molecular alterations, the dysregulation of the MYC oncogene has gained increasing attention. MYC is a pleiotropic transcription factor that controls various cellular processes such as proliferation, cell death, metabolism, senescence, angiogenesis, immune response, microenvironment remodelling and differentiation. MYC amplification, has been associated with poor clinical outcomes in osteosarcoma patients. Despite the identification of MYC as a potentially effective and safe therapeutic target, there is still no approved MYC inhibitor in the clinic.
OMO-103 is a truncated form of the human MYC protein, 91 amino acids long, with mutations that alter its dimerization specificity compared to MYC and enable OMO-103 to disrupt and displace the oncogenic MYC/MAX heterodimers from their DNA binding sites, acting as a very efficient MYC dominant negative. Among other mechanisms, OMO-103 can form heterodimers with wild-type MYC, sequestering it from its targets on the DNA. To date, OMO-103 has shown a positive safety profile in animals as well as in the Phase 1 part of the first in human study, with mainly grade 1 infusion-related reactions.
This open-label, unicentric, single-arm Phase 2 pilot study aims to serve as a proof-of-concept of OMO-103 safety and activity in patients with advanced high-grade osteosarcoma, as measured by progression-free survival rate at 16 weeks, response rate and quality of life. In addition,it will explore potential biomarkers.

Methods: Patients ≥12 years with locally advanced/metastatic high-grade osteosarcoma who have received at least one line of standard chemotherapy containing cisplatin and anthracycline, and no more than 2 previous lines, will be included. 10 evaluable patients will be enrolled. At least 30% of them will be < 18 years old.
Patients will be treated at the RP2D (6.5 mg/kg as a weekly IV infusion) of OMO-103 to estimate anti-tumour activity and further characterise the safety, tolerability, pharmacokinetics, and pharmacodynamics (PD) of OMO-103. The first three patients 12-15 years of age will undergo additional safety monitoring and pharmacokinetics (PK).
Disease will be assessed by RECIST v1.1 by CT/MRI +/- gammagraphy every 8 weeks for the first 8 months and every 12 weeks thereafter until confirmed disease progression. Patients will be treated until progression by RECIST v1.1 or intolerable toxicity.
Patients >16 years of age will need to provide a newly obtained tumour biopsy (either from the primary tumour or from metastases) during screening and on-treatment for translational research, as well as seriated blood samples for predictive and PD Biomarker signature.
Health-related quality of life (HRQoL) will be measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 items (EORTC-C30) for adult patients, and by the Pediatric Quality of Life Inventory (PedsQL) for patients between 12 and 17.

Results: N/A, N/A,N/A

Conclusion: N/A,N/A,N/A