On November 21, 2019 Medicenna Therapeutics Corp. (TSX: MDNA,OTCQB: MDNAF), a clinical stage immuno-oncology company, reported new positive results on drug distribution from the recently completed Phase 2b clinical trial of MDNA55 for the treatment of recurrent glioblastoma ("rGBM"), the most common and uniformly fatal form of brain cancer (Press release, Medicenna Therapeutics, NOV 21, 2019, View Source [SID1234551601]).
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The results were presented by Dr. Nicholas Butowski, MD, Professor of Neurological Surgery and Director of Translational Research in Neuro-Oncology at the Helen Diller Family Comprehensive Cancer Center, University of California San Francisco at the 3rd Society for Neuro-Oncology and Society for CNS Interstitial Delivery of Therapeutics Joint Conference ("SNO-SCIDOT") held on November 20, 2019 at the JW Marriott Desert Ridge Resort in Phoenix, Arizona. Dr. Butowski provided an update on drug delivery results from the MDNA55 clinical trial which uses a technique known as Convection Enhanced Delivery ("CED") to treat adults with rGBM.
"CED allows us to solve one of the fundamental problems in trying to treat patients with brain tumors, and that is delivery," states Dr. Butowski. "By implementing new advances in CED that were previously not available, we are able to bypass the blood-brain barrier and deliver high concentrations of MDNA55 directly to the tumor and the at-risk area immediately surrounding it, without exposure to the rest of the body. Delivering MDNA55 to where it needs to be, along with the ability to continuously monitor distribution using real-time imaging, allows us to dramatically improve drug delivery and maximize tumor coverage."
Highlights from the podium presentation include:
The MDNA55-05 study showed nearly 50% coverage of the tumor, with some patients achieving over 90% coverage of the target volume. In contrast, a previous CED study in rGBM1, without the advances implemented by Medicenna, was able to achieve coverage of only 18% of the tumor and a 1cm high-risk margin around it.
Higher infusion volumes (up to 66 mL) and higher doses of MDNA55 (up to 240 mg) did not result in increased toxicity.
In the first 33 patients enrolled in the clinical trial, subjects expressing high levels of the IL4 receptor (IL4R) showed promising overall survival at 12 months (OS-12) of 57%, compared to an OS-12 of 27% for patients expressing low levels of IL4R – an improvement of 111%.
The two IL4R groups did not reveal any differences in drug distribution or tumor coverage, highlighting the importance of IL4R expression in receiving optimal benefit from MDNA55.
"This trial clearly illustrates that directing therapy to a relevant target in rGBM, such as the IL4 receptor, is key in order to see improved patient outcomes," states Dr. Fahar Merchant, President and CEO of Medicenna. "We are optimistic that the combination of a targeted therapy and precision delivery of MDNA55 will enable us to provide maximum benefit to patients."
Updated efficacy results from the Phase 2b clinical trial MDNA55-05 will be presented on Sunday, November 24th, 2019 at the SNO Annual Meeting taking place immediately after the SNO-SCIDOT conference.
Reference:
Sampson JH, Archer G, Pedain C, Wembacher-Schröder E, Westphal M, Kunwar S, Vogelbaum MA, Coan A, Herndon JE, Raghavan R, Brady ML, Reardon DA, Friedman AH, Friedman HS, Rodríguez-Ponce MI, Chang SM, Mittermeyer S, Croteau D, Puri RK; PRECISE Trial Investigators. Poor drug distribution as a possible explanation for the results of the PRECISE trial. J Neurosurg. 2010 Aug;113(2):301-9.
About the MDNA55-05 Clinical Trial
MDNA55-05 is a Phase 2b study of the safety and efficacy of MDNA55, an IL4R-directed toxin, in patients with de novo GBM at first or second relapse where the tumor is not amenable to surgical resection. In the study, investigators administer MDNA55 once directly into the brain tumor using a technique known as Convection Enhanced Delivery (CED). CED allows precision delivery of MDNA55 into the tumor and the surrounding healthy brain containing infiltrative tumor cells, while avoiding systemic exposure.
The primary endpoint of the study is median Overall Survival (mOS) comparing a null survival rate of 8.0 months (based on historical control) with an alternative pursue rate of 11.5 months (1-sided alpha = 0.10 and 80% power for 46 ITT subjects). The secondary endpoint is objective response rate (ORR) assessed by the modified Response Assessment in Neuro-Oncology (mRANO)-based criteria incorporating advanced imaging modalities according to a null response rate of 6% with alternative pursue rate of 18% (1-sided alpha = 0.10 and 80% power for at least 35 subjects evaluable for response).