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

NCT02858895 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: MDNA55-05
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 7

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.

Conditions

Glioblastoma; Grade IV Astrocytoma; Glioblastoma Multiforme; Grade IV Glioma

Keywords

High grade glioma; malignant glioma; recurrent glioblastoma; recurrent GBM; recurrent GB; glioblastoma (GB); glioblastoma multiforme (GBM); progressive glioblastoma; Brain tumor; Brain cancer; immunotherapy; targeted; IL4R

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  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.

  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.

Secondary Outcomes (2)

• Objective Response Rate (ORR)

  12 months

• Progression Free Survival (PFS)

  12 months

Other Outcomes (4)

• Number of Subjects With Serious Adverse Events

  12 months

• Treatment Emergent Adverse Events

  12 months

• Level of MDNA55 in Peripheral Plasma

  14 days

Study Arms (1)

MDNA55

EXPERIMENTAL

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

Drug: MDNA55

Interventions

MDNA55 DRUG

MDNA55 is an engineered circularly permuted interleukin-4 (cpIL-4) genetically fused to the catalytic domain of the pseudomonas exotoxin A (PE).

Also known as: IL4-PE, Interleukin-4 Pseudomonas Exotoxin, Interleukin-4 Pseudomonas Toxin, IL4 Pseudomonas Exotoxin, NBI-3001, cpIL4-PE

MDNA55

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be ≥ 18 years old and have a life expectancy ≥ 12 weeks
• Histologically proven, primary (de novo) GB that has recurred or progressed (first or second recurrence, including this recurrence)
• Confirmation that archived tissue is available from first diagnosis of GB for biomarker analysis
• Recurrent tumor must be supratentorial, contrast-enhancing GB no smaller than 1 cm x 1 cm (largest perpendicular dimensions) and no larger than 4 cm maximum in a single direction based on MRI taken within 14 days prior to catheter placement
• Karnofsky Performance Score (KPS) ≥ 70
• Subjects must be able and willing to undergo multiple brain MRI examinations
• Subjects must be able and willing to comply with all study procedures

You may not qualify if:

• Prior treatment with cytotoxic chemotherapy
• Temozolomide (standard induction and / or maintenance dosing) within the past 4 weeks prior to planned infusion
• "Metronomic" Temozolomide (low-dose, continuous administration) within the past 7 days prior to planned infusion
• Nitrosoureas within the past 6 weeks prior to planned infusion
• Treatment with any other cytotoxic agent within the past 4 weeks prior to planned infusion
• Prior investigational treatment within the past 4 weeks or prior immunotherapy or antibody therapy within the past 4 weeks prior to planned infusion
• Prior treatment with bevacizumab (Avastin) or other vascular-endothelial growth factor (VEGF) inhibitors or VEGF-receptor signaling inhibitors within the past 4 weeks prior to planned infusion
• Prior therapy that included interstitial brachytherapy or Gliadel® Wafers (carmustine implants) within the past 12 weeks prior to planned infusion
• Prior surgery (including stereotactic radiosurgery and biopsy procedures) within the past 4 weeks prior to planned infusion
• Ongoing Optune© therapy within 5 days of planned infusion
• Secondary GB (i.e., GB that progressed from low-grade diffuse astrocytoma or AA)
• Known mutation in either the isocitrate dehydrogenase 1 (IDH1) or the IDH2 gene.
• Tumor in the brainstem (not including fluid-attenuated inversion recovery \[FLAIR\] changes), an infratentorial tumor, diagnosis of gliomatosis cerebri (highly infiltrative T2 hyperintense tumor with ill-defined margins encompassing at least three lobes of the brain.
• Tumor with a mass effect (e.g. 1-2 cm midline shift)
• Subjects with tumors for which the preponderance of tissue is not of the type in which convection would be possible (e.g. preponderance of cystic component)

Sponsors & Collaborators

• Medicenna Therapeutics, Inc.: lead

Study Sites (7)

University of California San Francisco

San Francisco, California, 94143, United States

Location

John Wayne Cancer Institute at Providence Saint John's Health Center

Santa Monica, California, 90404, United States

Location

Boca Raton Regional Hospital

Boca Raton, Florida, 33486, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

Location

Cancer Therapy and Research Center at The University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Related Publications (2)

• Sampson JH, Singh Achrol A, Aghi MK, Bankiewicz K, Bexon M, Brem S, Brenner A, Chandhasin C, Chowdhary S, Coello M, Ellingson BM, Floyd JR, Han S, Kesari S, Mardor Y, Merchant F, Merchant N, Randazzo D, Vogelbaum M, Vrionis F, Wembacher-Schroeder E, Zabek M, Butowski N. Targeting the IL4 receptor with MDNA55 in patients with recurrent glioblastoma: Results of a phase IIb trial. Neuro Oncol. 2023 Jun 2;25(6):1085-1097. doi: 10.1093/neuonc/noac285.

  PMID: 36640127 DERIVED

• Ellingson BM, Sampson J, Achrol AS, Aghi MK, Bankiewicz K, Wang C, Bexon M, Brem S, Brenner A, Chowdhary S, Floyd JR, Han S, Kesari S, Randazzo D, Vogelbaum MA, Vrionis F, Zabek M, Butowski N, Coello M, Merchant N, Merchant F. Modified RANO, Immunotherapy RANO, and Standard RANO Response to Convection-Enhanced Delivery of IL4R-Targeted Immunotoxin MDNA55 in Recurrent Glioblastoma. Clin Cancer Res. 2021 Jul 15;27(14):3916-3925. doi: 10.1158/1078-0432.CCR-21-0446. Epub 2021 Apr 16.

  PMID: 33863808 DERIVED

Related Links

• Sponsor website

MeSH Terms

Conditions

Glioblastoma; Glioma; Brain Neoplasms

Interventions

interleukin-4-Pseudomonas exotoxin

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Rosemina Merchant - Chief Development Officer
• Organization: Medicenna Therapeutics Inc

nmerchant@medicenna.com

604-340-3081

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2016
• First Posted: August 8, 2016
• Study Start: April 11, 2017
• Primary Completion: September 12, 2019
• Study Completion: October 31, 2019
• Last Updated: October 24, 2022
• Results First Posted: October 24, 2022

Record last verified: 2022-10

Locations

US (7)