Medidata AI & Imunon Publish Findings in ASCO Journal of Clinical Oncology that Show a Historic Clinical Trial External Control Arm Provides an Actionable Efficacy Estimate Prior to a Randomized Trial
Medidata and Imunon Corporation—a clinical-stage company focused on DNA-based immunotherapy and next-generation vaccines—published their findings on the use of a Synthetic Control ArmⓇ (SCA) in a completed Phase Ib dose-escalating study of GEN-1 in the neoadjuvant treatment of patients with Stage III/IV ovarian cancer (the OVATION 1 Study) in the American Society of Clinical Oncology (ASCO) Journal of Clinical Oncology.
The research team, comprised of Xiang Yin, PhD, Ruthie Davi, PhD, Elizabeth B. Lamont, MD, MS, Premal H. Thaker, MD, MS, William H. Bradley, MD, Charles A. Leath, III, MD, MSPH, Kathleen M. Moore, MD5, Khursheed Anwer, PhD, MBA, Lauren Musso, and Nicholas Borys, MD, demonstrated that comparing patients from a single-arm study can:
- Enhance understanding of treatment effects in advance of randomized clinical trials
- Inform drug development and clinical trial design
- Increase the scientific value of early-phase clinical trials
The Phase Ib OVATION 1 Study evaluated escalating doses of GEN-1 (36 mg/m2, 47 mg/m2, 61 mg/m2 and 79 mg/m2) administered intraperitoneally in combination with three cycles of neoadjuvant chemotherapy (NACT) prior to interval debulking surgery. This was followed by three cycles of NACT in the treatment of newly diagnosed patients with Stage III/IV ovarian cancer.
GEN-1—designed using Imunon’s proprietary TheraPlasTM platform technology—is an interleukin-12 (IL-12) DNA plasmid vector encased in a non-viral nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein.
“The Medidata AI Synthetic Control Arm provided reliable estimates of the efficacy endpoints, which allowed for a decrease in the number of patients needed to participate in the subsequent randomized Phase II trial. In addition to decreasing the burden on patients, this helped to accelerate trial timelines and decrease costs,” said Dr. Nicholas Borys, Chief Medical Officer at Imunon. “This truly important progress will lead to further insights and advancements in future trials and, in the end, help bring treatments to patients faster.”
A Synthetic Control Arm is a type of external control formed by carefully matching patients treated with a new investigational therapy to anonymized clinical trial patients from Medidata’s extensive repository of historical clinical trials using baseline demographic and disease characteristics. Using this advanced statistical methodology, Imunon and Medidata found that progression-free survival was prolonged for the patients treated with the investigational therapy GEN-1 along with standard of care chemotherapy in the OVATION 1 Study compared to well-balanced historic control patients treated with the same standard of care chemotherapy alone (Hazard Ratio=0.53, 95% Confidence Interval (0.16, 1.73).
This larger than expected effect size led to a decrease in the number of planned patients for Imunon’s subsequent Phase II trial and was used in support of Fast Track Designation from the U.S. Food and Drug Administration (FDA) received in February 2021.
“Medidata AI is in a unique position to create fit-for-purpose synthetic controls because of access to a pool of more than eight million anonymized patients from 28,000+ previous clinical trials,” said Ruthie Davi, Ph.D., Vice President of Data Science at Medidata AI. “Our findings show that an SCA can provide a scientifically rigorous comparison in scenarios where a control group is not part of the study design or hard to recruit or retain. We are proud to be working to decrease the patient burden, enhance scientific value, and accelerate studies.”
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