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Tumor Models Boston 2023

Identification of synergistic combination of molecular targeted agents and chemotherapy using TumorGraft3D & the Lumin Bioinformatics platform



Vaishnavi Sambandam, Ayelen Bulloj, Salma Shaik, Samaneh Kamali, Taylor Light, Matthew Grim, Clare Killick-Cole, Jon Katz, Antonella Chiechi, Mara Gilardi, Stefano Cairo, Marianna Zipeto, Abhay Andar, Karin Abarca Heidemann, Maria Mancini, Mike Ritchie



The advent of targeted therapy based on advanced molecular profiling has revolutionized
the way cancer patients are treated. A successful example is the use of tyrosine kinase
inhibitors (TKIs) for non-small-cell lung cancer (NSCLC) and melanoma. Unfortunately, the tumor often becomes resistant to these agents after the initial therapeutic benefit.
The majority of epidermal growth factor receptor (EGFR) mutations in NSCLC occurs in
exons 18-21 of the tyrosine kinase domain of the receptor. The T790M substitution within
exon 20, is a leading contributor to resistance to first- and second-generation EGFR
inhibitors in NSCLC. Osimertinib is an oral, third-generation EGFR-TKI designed to
overcome T790M-driven EGFR-TKI resistance while targeting the initial EGFR-activating

In melanoma patients, BRAF mutations occur frequently (more than 80% of cases).
Vemurafenib is an FDA-approved targeted therapy for BRAF-mut melanoma. Different
mechanisms characterize EGFR and BRAF acquired resistance and the knowledge of these
will help develop new therapies for overcoming acquired resistance.

Champions Oncology’s TumorGraft3D platform utilizes multiclonal 3D tumor cultures
derived from well-characterized patient-derived xenograft (PDX) models for ex vivo drug

This platform adopts a unique assay with no matrix added and uses indication-specific
media to allow for TumorGraft3D formation and proliferation. These are actively proliferating
3D models that faithfully recapitulate their parent PDXs are ideal for testing single-agent and
combination drug efficacy.

We employed our TumorgGraft3D platform to test osimertinib in 2 NSCLC models, one
EGFR-mut and one EGFR-wt, and vemurafenib in 2 BRAF-mut melanoma models. We used
the Lumin Bioinformatics Pharmacology Analysis tool to evaluate the efficacy and
synergistic effect of combining osimertinib and cisplatin in the EGFR-wt NSCLC
TumorGraft3D model.