Identification of synergistic combination of molecular targeted agents and chemotherapy using TumorGraft3D and the Lumin Platform

Targeted therapies, such as tyrosine kinase inhibitors (TKIs) for non-small-cell lung cancer (NSCLC) and melanoma, have transformed cancer treatment. However, resistance to these therapies, like the T790M mutation in EGFR for NSCLC and BRAF mutations in melanoma, limits their long-term effectiveness. Osimertinib, a third-generation EGFR-TKI, is designed to overcome T790M-driven resistance, while vemurafenib targets BRAF-mutated melanoma. Champions Oncology’s TumorGraft3D platform uses patient-derived xenograft (PDX)-derived 3D cultures to test drug efficacy, including single-agent and combination therapies, and is ideal for evaluating treatments like osimertinib and vemurafenib in NSCLC and melanoma models.

• Champion’s EGFR-mut and EGFR-wt NSCLC and BRAF-mut melanoma TumorGraft3D models are highly proliferative and form tight 3D structures in culture.

• EGFR-mut NSCLC model CTG3D-2842 showed higher sensitivity to osimertinib compared to EGFR-wt model CTG3D-0165, as expected based on osimertinib mechanism of action.

• Synergy analysis of osimertinib and cisplatin combination in EGFR-wt model CTG3D-0165 showed a synergistic effect of the two agent. These results support recent evidence of the potential benefit of combining chemotherapy and osimertinib for the treatment of patients with EGFR-wt NSCLC (3,4) and warrant further investigation.