Cellworks Biosimulation Predicts Chemotherapy Benefit in Osimertinib-treated NSCLC Patients with EGFR Mutations
September 09 2024 - 1:46PM
Business Wire
Study Uncovers Biomarkers Linked to
Chemotherapy Response in NSCLC Patients Carrying EGFR Variants
Cellworks Group Inc., a leader in Personalized Therapy Decision
Support and Precision Drug Development, today announced findings
from a study using the Cellworks Platform to predict the benefits
of adding chemotherapy to osimertinib treatment in patients with
EGFR mutated non-small cell lung cancer (NSCLC). Leveraging data
from a real-world retrospective cohort, the biosimulation study
confirmed that adding chemotherapy to osimertinib led to a higher
predicted overall response rate (ORR). The study revealed that
while all patients responded to the addition of chemotherapy, the
magnitude of benefit varied among individuals and was intricately
determined by underlying genomic abnormalities, enabling the
identification of patients who would benefit from combination
therapies, and others who would achieve similar outcomes without
the addition of chemotherapy.
Results from the study were showcased in a poster presentation
(P1.06A.03) titled ‘Use of Biosimulation to Predict Concomitant
Chemotherapy Benefit in NSCLC Patients with EGFR Mutations Being
Treated with Osimertinib’ as part of the IASLC 2024 World
Conference on Lung Cancer hosted by the International Association
for the Study of Lung Cancer in San Diego, California on September
8, 2024.
“Osimertinib has become a standard treatment option in patients
with NSCLC harboring EGFR mutations,” said Dr. Charu Aggarwal, MD,
MPH, Professor of Medicine, University of Pennsylvania, Associate
Director, PC3I and Director, Program in Precision Oncology
Innovation, Penn Center for Cancer Care Innovation; and Principal
Investigator for the study. “However, while targeted therapies are
generally effective for these patients, response rates can vary
significantly, and the potential advantage of incorporating
chemotherapy in some patients remains unclear. This study
demonstrates how utilizing Cellworks biosimulation can provide
valuable insights by more accurately predicting the benefit of
chemotherapy, as it allows for a deeper understanding of an
individual patient's therapy response based on biosimulation of
their full mutation profile.”
“This study opens new potential avenues for optimizing treatment
strategies in NSCLC patients with EGFR mutations,” said Dr. Michael
Castro, Cellworks Chief Medical Officer. “By identifying additional
biomarkers that influence chemotherapy response in NSCLC patients,
we gain a deeper understanding of how each patient’s unique disease
profile impacts therapy effectiveness. EGFR blockade can reverse
chemotherapy resistance for some patients by downregulating
apoptotic blockade and DNA repair caused by EGFR. Through the use
of Cellworks personalized therapy biosimulation, we can pave the
way for individualized decision making to determine which patients
should be offered combination therapy upfront, thereby improving
survival outcomes.”
Study Design
Cellworks computational biosimulation was performed in this
study to evaluate the additive value of chemotherapy in patients
with advanced non-small cell lung cancer (NSCLC) with EGFR
mutations. A real-world retrospective cohort of 116 frontline NSCLC
patients treated with osimertinib were obtained from the nationwide
(US based) de-identified Flatiron Health-Foundation Medicine NSCLC
clinico-genomic database (FH-FMI-CGDB). Biosimulated efficacy
scores were generated for both osimertinib alone and in combination
with carboplatin and pemetrexed. The study then analyzed
chemotherapy-driven improvements in predicted clinical response,
using the upper 95% confidence interval of the osimertinib ES as a
threshold.
Study Results
The efficacy scores for osimertinib were significantly
associated with clinical outcomes, confirming the predictive power
of Cellworks computational biosimulation. Importantly, the
biosimulated addition of chemotherapy to osimertinib led to a
higher efficacy score for some patients, allowing for a more
refined selection of patients, moving beyond the generalized
conclusion that chemotherapy is beneficial in combination, which
may apply to some, but not all, patients. The benefit of
chemotherapy is unevenly distributed in the population, and
biosimulation aids in the selection of which patients are most
likely to get a benefit from combination compared to sequential
treatment.
The Cellworks Platform
The Cellworks Platform biosimulates the impact of specific drug
compounds on an individual patient or class of patients using their
multi-omic profile. Multi-omic data from an individual patient or
cohort is used as input to the in silico Cellworks Computational
Biology Model (CBM) to generate a personalized or cohort-specific
disease model. The CBM is a highly curated mechanistic network of
6,000+ human genes, 30,000 molecular species and 600,000 molecular
interactions. This model along with associated drug models are used
to biosimulate the impact of specific compounds or combinations of
drugs on the patient or cohort and produce therapy response
predictions, which are statistically modeled to produce a
qualitative Therapy Response Index (TRI) score, scaled from 0
(unfavorable outcome) to 100 (favorable outcome) for a specific
therapy. The Cellworks CBM has been tested and applied against
various clinical datasets with results provided in over 125
presentations and publications with global collaborators.
About Cellworks Group
Cellworks Group, Inc. is a leader in Personalized Therapy
Decision Support and Precision Drug Development. The Cellworks
Platform predicts therapy response for individual patients and
patient cohorts using a breakthrough Computational Biology Model
(CBM) and biosimulation technology. Backed by Artiman Ventures,
Bering Capital, Sequoia Capital, UnitedHealth Group and Agilent
Ventures, Cellworks has the world’s strongest trans-disciplinary
team of molecular biologists, cellular pathway modelers and
software engineers working toward a common goal – attacking serious
diseases to improve the lives of patients. The company is based in
South San Francisco, California with a CLIA-certified computational
laboratory in Franklin, Tennessee and a research and development
facility in Bangalore, India. For more information, visit
www.cellworks.life.
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