Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Recurrent or Progressive Glioblastoma

Phase 2

Completed

• Conditions: Glioblastoma; Glioblastoma Multiforme; Grade IV Glioma; Grade IV Astrocytoma
• Interventions: Drug: MDNA55

• Registration Number: NCT02858895
• Lead Sponsor: Medicenna Therapeutics, Inc.

Brief Summary

This is a single-arm, open-label, multicenter study in approximately 52 adults with primary (de novo) GB that has recurred or progressed (first or second recurrence, including this recurrence) after treatment(s) including surgery and radiotherapy with or without chemotherapy and following discontinuation of any previous standard or investigational lines of therapy.

Detailed Description

The study drug, MDNA55, is a fusion protein comprising a genetically engineered Interleukin-4 (IL-4) linked to a modified version of the Pseudomonas aeruginosa exotoxin A (PE). MDNA55 binds to the IL-4 receptor (IL4R), over-expressed by cancer cells and non-malignant immunosuppressive cells of the tumor microenvironment (TME), and delivers a potent cell-killing agent, PE.

The study will be conducted at up to 10 clinical sites following institutional review board approval and completed informed consent.

Subjects that meet the study eligibility criteria will undergo surgery associated with study drug administration. MDNA55 will be administered locally by convection-enhanced delivery (CED).

Post-treatment follow-up assessment of safety and efficacy will be performed monthly for the first 6 months and bimonthly thereafter for approximately 1 year after study drug administrations. Subjects will continued to be followed for survival and post-study treatment(s) of GB after study completion or withdrawal.

Study Timeline

• Study First Submitted: 2016-07-28
• Study First Submitted QC: 2016-08-03
• Study First Posted: 2016-08-08
• Study Start: 2017-04-11
• Primary Completion: 2019-09-12
• Study Completion: 2019-10-31
• Disposition First Submitted: 2021-01-13
• Results First Submitted: 2022-07-08
• Status Verified: 2022-10
• Results First Submitted QC: 2022-10-18
• Disposition First Submitted QC: 2022-10-18
• Last Update Submitted: 2022-10-18
• Results First Posted: 2022-10-24
• Disposition First Posted: 2022-10-24
• Last Update Posted: 2022-10-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 47

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MDNA55	MDNA55	Single infusion of MDNA55 via convection enhanced delivery (CED).\* \*Subjects may be eligible to receive a second administration of MDNA55.

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS)	From start of treatment until date of death from any cause. Subjects who were not known to have died at the time of the analysis were to be censored at the date of last contact.	Primary endpoint analysis was based on the ITT population. The null hypothesis was mOS of 8.0 months, based on a clinically-weighted average of published studies of FDA-approved therapies versus the alternative hypothesis of 11.5 months.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	12 months	ORR, determined by independent central review (per RANO-based criteria) Complete Response - Disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks.; Partial Response - ≥50% decrease in sum of products of perpendicular diameters or ≥65% decrease in total volume of all measurable enhancing lesions compared with baseline, sustained for at least 4 weeks Progressive Disease - At least two sequential scans separated by at ≥4 weeks both exhibiting ≥25% increase in sum of products of perpendicular diameters or ≥40% increase in total volume of enhancing lesions.; Stable Disease - Does not qualify for CR, PR, or PD as defined above
Progression Free Survival (PFS)	12 months	PFS, time from treatment until disease progression (per RANO-based criteria) or death Progressive Disease per RANO - At least two sequential scans separated by at ≥4 weeks both exhibiting ≥25% increase in sum of products of perpendicular diameters or ≥40% increase in total volume of enhancing lesions

Trial Locations

Locations (7)

John Wayne Cancer Institute at Providence Saint John's Health Center; 🇺🇸 Santa Monica, California, United States

Hospital of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Cancer Therapy and Research Center at The University of Texas Health Science Center at San Antonio; 🇺🇸 San Antonio, Texas, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

Boca Raton Regional Hospital; 🇺🇸 Boca Raton, Florida, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States