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

Sponsor

Medicenna Therapeutics, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02858895

Collaborator

(none)

Enrollment

Locations

Arm

30.7

Actual Duration (Months)

6.6

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma Grade IV Astrocytoma Glioblastoma Multiforme Grade IV Glioma	Drug: MDNA55	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

46 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-Label Non-Randomized, Multi-Center Phase-2 Study of Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Recurrent or Progressive Glioblastoma

Actual Study Start Date :

Apr 11, 2017

Actual Primary Completion Date :

Sep 12, 2019

Actual Study Completion Date :

Oct 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MDNA55 Single infusion of MDNA55 via convection enhanced delivery (CED).* *Subjects may be eligible to receive a second administration of MDNA55.	Drug: MDNA55 MDNA55 is an engineered circularly permuted interleukin-4 (cpIL-4) genetically fused to the catalytic domain of the pseudomonas exotoxin A (PE). Other Names: IL4-PE Interleukin-4 Pseudomonas Exotoxin Interleukin-4 Pseudomonas Toxin IL4 Pseudomonas Exotoxin NBI-3001 cpIL4-PE

Arm

Intervention/Treatment

Experimental: MDNA55

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

Drug: MDNA55

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

Other Names:

IL4-PE

Interleukin-4 Pseudomonas Exotoxin

Interleukin-4 Pseudomonas Toxin

IL4 Pseudomonas Exotoxin

NBI-3001

cpIL4-PE

Outcome Measures

Primary Outcome Measures

Overall Survival (OS) [12 months]
OS, time from treatment until death

Secondary Outcome Measures

Objective Response Rate (ORR) [12 months]
ORR, determined by independent central review (per RANO-based criteria)
Progression Free Survival (PFS) [12 months]
PFS, time from treatment until disease progression (per RANO-based criteria) or death

Other Outcome Measures

Serious adverse events (SAEs) [12 months]
Incidence of SAEs
Treatment emergent adverse events (AEs) [12 months]
Incidence of Treatment-Emergent AEs
Pharmacokinetics (PK) of MDNA55 [14 days]
Blood samples will be collected to determine levels of MDNA55
Anti-MDNA55 antibody [12 months]
Blood samples will be collected to determine anti-drug antibody titers

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

INCLUSION CRITERIA:

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
Any related toxicities following discontinuation of prior GB therapies must have resolved to CTCAE Grade 1 or lower prior to inclusion in this study

EXCLUSION CRITERIA:

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)
Tumor with geometric features that make them difficult to adequately cover the tumor volume with infusate by using CED catheters
Clinical symptoms that are thought by the Investigator to be caused by uncontrolled increased intracranial pressure, hemorrhage, or edema of the brain
Any condition that precludes the administration of anesthesia
Known to be human immunodeficiency virus positive
Concurrent or a history of any significant medical illnesses that in the Investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the subject's ability to tolerate the study drug therapy and/or put the subject at additional risk or interfere with the interpretation of the results of this trial
Known history of allergy to gadolinium contrast agents
Presence of another type of malignancy requiring treatment within < 3 years prior to the screening visit, except for adequately treated carcinoma in-situ of the cervix, prostate cancer not actively treated, and basal or squamous cell carcinoma of the skin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Francisco	San Francisco	California	United States	94143
2	John Wayne Cancer Institute at Providence Saint John's Health Center	Santa Monica	California	United States	90404
3	Boca Raton Regional Hospital	Boca Raton	Florida	United States	33486
4	Duke University Medical Center	Durham	North Carolina	United States	27710
5	Oregon Health & Science University	Portland	Oregon	United States	97239
6	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19107
7	Cancer Therapy and Research Center at The University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229