Charting a path for prioritization of novel agents for clinical trials in osteosarcoma: A report from the Children's Oncology Group New Agents for Osteosarcoma Task Force

Area of Science:

• Pediatric Oncology
• Bone Tumors
• Cancer Therapeutics

Background:

• Osteosarcoma is the most common primary bone malignancy in children and young adults.
• Metastatic and relapsed osteosarcoma have a poor prognosis with limited treatment advancements.
• Challenges include biological complexity, lack of specific drugs, inadequate preclinical models, and trial design limitations.

Purpose of the Study:

• To establish a systematic approach for identifying and prioritizing novel therapeutic agents for osteosarcoma.
• To address the stagnation in improving outcomes for patients with osteosarcoma.
• To guide the selection of agents for future clinical trials.

Main Methods:

• The Children's Oncology Group Bone Tumor Committee formed the New Agents for Osteosarcoma Task Force.
• The task force identified and prioritized potential therapeutic agents based on defined criteria.
• Agents evaluated included multitargeted tyrosine kinase inhibitors, B7-H3 immunotherapies, CD47-SIRPα inhibitors, telaglenastat, and epigenetic modifiers.

Main Results:

• Multitargeted tyrosine kinase inhibitors were the only agents meeting all criteria for frontline evaluation.
• These inhibitors have been incorporated into an upcoming Phase III study concept.
• Other identified agents remain of interest pending further data.

Conclusions:

• A structured prioritization process is crucial for advancing osteosarcoma treatment.
• Multitargeted tyrosine kinase inhibitors represent a promising frontline strategy for osteosarcoma.
• Ongoing evaluation of novel agents and adaptive trial designs are essential for future progress.