On May 29, 2020 Medicenna Therapeutics Corp. ("Medicenna" or "the Company") (TSX: MDNA,OTCQB: MDNAF), a clinical stage immuno-oncology company, reported virtual presentations of data from its completed Phase 2b trial of MDNA55, an IL4-guided toxin, in patients with recurrent Glioblastoma (rGBM), at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Medicenna Therapeutics, MAY 29, 2020, View Source [SID1234558764]).
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The oral poster discussion led by Dr. Ian F. Parney, MD, PhD (Mayo Clinic) and a presentation by Dr. John Sampson, MD, PhD (Robert H. and Gloria Wilkins Distinguished Professor of Surgery, Duke University School of Medicine), focused on additional data demonstrating clinical superiority of MDNA55 in patients with rGBM. The study enrolled rGBM patients that had aggressive tumors (de novo GBM, IDH wild-type, not-resectable at recurrence) with limited treatment options and poor survival outcomes [median overall survival ("mOS") of 6-9 months, median progression free survival ("mPFS") of < 2months and progression free survival ("PFS") at twelve months ("PFS-12") of 0%].
"Currently there are no approved therapies for rGBM that can extend survival by 50%, let alone by 70 – 100% as seen with MDNA55 after just one treatment," said Dr. John Sampson. "The data presented here reinforces our conviction that MDNA55 is an important player in glioblastoma and is a promising treatment option for this devastating disease."
"We’ve long believed that MDNA55 has the potential to present as a superior treatment option for improved survival and tumor control in patients with recurrent glioblastoma," says Dr. Fahar Merchant, President and Chief Executive Officer, Medicenna Therapeutics. "Further refinement of new and previously reported data using a rigorous propensity-matching methodology to remove any potential selection bias further bolsters this belief. For a treatment area that has seen limited innovation for more than 20 years, the MDNA55 phase 2 clinical trial data demonstrates strong evidence that MDNA55 could change the treatment paradigm for rGBM." The Company plans to submit an end of Phase 2 meeting package for MDNA55 to the FDA in Q2 2020.
Highlights from the ASCO (Free ASCO Whitepaper) presentation included:
Comparison of MDNA55 with an eligibility-matched Synthetic Control Arm ("SCA") demonstrated an improvement in mOS of 61%. When stratified by IL4R status, IL4R High subjects in the MDNA55 arm demonstrated improved mOS by 155% (Table 1).
Table 1.
Eligibility-Matched
Groups
N
mOS
Improvement
in mOS
Hazard
Ratio (HR)
OS-12
MDNA55 All-comers
44
12.4
61%
0.58
53%
SCA All-comers
81
7.7
25%
MDNA55 IL4R High
21
15.8
155%
0.54
62%
SCA IL4R High
17
6.2
24%
Further refinement of the SCA using propensity-score weighting (Li et al), an unbiased approach to select patients that match the baseline characteristics of MDNA55 treated patients based on 11 key baseline prognostic factors, confirms these results (Table 2).
Table 2.
Propensity-Weighted
Groups
N
mOS
Improvement
in mOS
HR
MDNA55 All-comers
43
12.4
72%
0.63
SCA All-comers
40.8
7.2
MDNA55 IL4R High
17
13.2
116%
0.52
SCA IL4R High
16.8
6.1
Irrespective of IL4R expression, subjects showed tumor control rate ("TCR") (tumor shrinkage or stabilization) of 76% based on modified RANO criteria; these subjects demonstrated mPFS of 4.6 months, PFS at six months ("PFS-6") of 40%, PFS-12 of 33%, mOS of 15.0 months and overall survival at twelve months ("OS-12") of 57%.
Additional updated results (not presented at ASCO (Free ASCO Whitepaper)) include the following:
Patients with Low IL4R expression (H-Score ≤ 60) had a similar TCR as patients with High IL4R expression (H-Score > 60); TCR of 75% vs. 76%, respectively. However, the majority of the IL4R Low patients (11 of 16) received high doses of MDNA55 (180 – 240 mg; median 180 mg) whereas only 8 of 21 IL4R High patients received the high dose of MDNA55.
The IL4R Low group receiving high dose also showed improved survival (mOS Not Reached, OS-12 of 53%) when compared to the low dose group (mOS = 8 months, OS-12 = 13%).
The Proposed Population (n=32), comprised of all IL4R High (irrespective of dose) as well as IL4R Low patients receiving the high dose, were shown to benefit the most from a single treatment of MDNA55. Median survival and OS-12 in this population was 15.8 months and 62% vs 7.0 months and 18%, respectively, when compared to the eligibility matched SCA. (Table 3).
Table 3.
TCR in the Proposed Population was 81% based on radiologic assessment by mRANO criteria.
These data indicate that MDNA55 has the potential to benefit all rGBM patients treated at the high dose (180 mg) irrespective of IL4R expression. The high dose has already shown an acceptable safety profile in this and earlier clinical trials (MTD = 240 mg).
The presentation and poster is available for on-demand viewing online at:
View Source
Reference:
Li F, Zaslavsky AM, Landrum MB. Propensity score weighting with multilevel data. Stat Med. 2013 Aug 30;32(19):3373-87.