MG1 Maraba/MAGE-A3, With and Without Adenovirus Vaccine With Transgenic MAGE-A3 Insertion in Incurable MAGE-A3-Expressing Solid Tumours

NCT02285816 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: I214
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 4

Brief Summary

This research is being done because these viruses have been shown to shrink tumours in animals and human tumour samples by selectively killing cancer cells and creating an immune response to the tumour antigen contained in the viruses. This effect has been shown to increase when the AdMA3 virus is given first. It is not clear if this treatment will offer better results than standard treatment.

Conditions

Advanced/Metastatic Solid Tumours

Outcome Measures

Primary Outcomes (2)

• Phase I: Toxicity as measured by adverse events

  To Determine maximum feasible dose (MFD) of: * MG1MA3 when administered alone on day 1 \& day 4 (Arm A) * MG1MA3 when administered on day 1 \& 4 or days 1, 4, 8 \&11 following immunologic priming with AdMA3 (Arm C) * To confirm the safety profile of AdMA3 administration (Arm B).

  3 years

• Phase II: Objective tumour response rate (ORR) using RECIST v1.1.

  To evaluate the objective tumour response rate (ORR) using RECIST v1.1.

  16 weeks

Secondary Outcomes (9)

• Phase I: Number and Severity of Adverse Events in patients

  8 weeks

• Phase I: MG1MA3 clearance and secondary replication from pharmacokinetics and viral shedding

  3 years

• Phase I: Delivery to, and viral detection and replication within, tumours for MG1MA3

  3 years

• Phase I: Cellular and humoral immune response to virus and tumour antigens

  3 years

• Phase I: Efficacy using RECIST v1.1 and iRECIST

  3 years

Study Arms (3)

Arm A (MG1MA3 virus alone)

EXPERIMENTAL

The starting dose of MG1MA3 will be 1 x 10\^10 pfu administered by IV on day 1 and day 4.MG1MA3 dose will be escalated as per protocol.

Biological: MG1MA3

Arm B- AdMA3 (vaccine prime) alone

EXPERIMENTAL

Six patients will receive prime AdMA3 vaccine at a dose of 1x10\^10 pfu administered IM on day (-14). No dose escalation is planned.

Biological: AdMA3

Arm C- AdMA3 plus MG1MA3 (prime + boost)

EXPERIMENTAL

Prime AdMA3 vaccine will be administered as a single dose of 1x10\^10 pfu IM at day (-14) followed by dose escalation of MG1MA3 boost, IV administered on days 1 \& 4 at a starting dose of 1 log below the recommended phase II dose (RP2D), as determined in Arm A of this study. MG1MA3 dose will be escalated as defined in protocol.

Biological: MG1MA3; Biological: AdMA3

Interventions

MG1MA3 BIOLOGICAL

MG1MA3: Boosting component of Oncolytic Vaccine

Also known as: MG1 Maraba/MAGE-A3

Arm A (MG1MA3 virus alone); Arm C- AdMA3 plus MG1MA3 (prime + boost)

AdMA3 BIOLOGICAL

AdMA3: Priming component of Oncolytic Vaccine

Also known as: Adenovirus/MAGE-A3

Arm B- AdMA3 (vaccine prime) alone; Arm C- AdMA3 plus MG1MA3 (prime + boost)

Eligibility Criteria

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

You may qualify if:

• PHASE I: Patients must have histologically confirmed, unresectable locally advanced/metastatic solid tumour with positive expression of MAGE-A3 (primary or metastatic lesion) and for which there is no known life prolonging standard therapy.
• PHASE II: Patients must have histologically confirmed, unresectable locally advanced/metastatic solid tumour with positive expression of MAGE-A3 (primary or metastatic lesion) as follows:
• Non-small cell lung cancer (NSCLC) specifically adenocarcinoma and squamous cell carcinoma.
• Breast cancer
• Esophageal/GEJ cancer/gastric
• In phase II patients may be treated before refractory, such as while stable post treatment response to first line therapy.
• Presence of clinically and/or radiologically documented disease. At least one site of disease must be unidimensionally measurable by CT with IV contrast as follows:
• Chest x-ray ≥ 20 mm
• CT scan (with slice thickness of ≤ 5 mm) ≥ 10 mm--\>Longest diameter
• Physical exam (using calipers) ≥ 10 mm
• Lymph nodes by CT scan ≥ 15 mm --\>Measured in short axis
• All radiology studies must be performed within 14 days prior to registration (within 21 days if negative).
• Patients must have at least one additional tumour mass amenable to core needle or excisional biopsy (Note FNA is not acceptable) that is not a measurable lesion that will be used as a target lesion. Patients must consent to and be willing and able to undergo at least two core needle biopsies of that lesion.
• Age ≥ 18 years
• ECOG performance status of 0 or 1

You may not qualify if:

• Patients with a history of other active or current malignancies that require active treatment
• Patients with known symptomatic brain metastases. Patients with treated and radiologic or clinical evidence of stable brain metastases, are eligible providing that they have been stable for at least 3 months, are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 1 month prior to entry).
• Patients receiving concurrent treatment with other anti-cancer therapy or other investigational agents.
• Patients who have had prior treatment with AdVAC, MG1MA3 or any MAGE-A3 targeted therapy.
• Pregnant or lactating women. Men and women of childbearing potential who do not agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of the study participation.
• Serious illness or medical condition which would not permit the patient to be managed according to the protocol, including, but not limited to:
• History of significant neurologic or psychiatric disorder (e.g. uncontrolled psychotic disorders) which would impair the ability to obtain consent or limit compliance with study requirements.
• Active uncontrolled or serious infection (viral, bacterial or fungal) or a history of opportunistic infection associated with an immunodeficient state.
• Significant immunodeficiency due to underlying illness (e.g. known HIV/AIDS) and/or medication (e.g. systemic corticosteroids).
• Known myeloproliferative disorders requiring systemic therapy.
• Other medical conditions that might be aggravated by study treatment.
• Patients with uncontrolled pre-existing cardiovascular conditions and/or symptomatic cardiac dysfunction.
• Patients with household contacts meeting any of the following criteria are ineligible for study entry unless alternate living arrangements can be made:
• Women who are pregnant or nursing an infant
• Children \< 12 months old

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• Ottawa Hospital Research Institute: collaborator

Study Sites (4)

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (3)

• Mullins-Dansereau V, Myre ML, Bardoul A, Geoffroy K, Rallo Pita MJ, Beland D, Desaulniers KL, Roy DG, Bourgeois-Daigneault MC. Oncolytic VSV-IL-2 has enhanced anticancer vaccination adjuvant abilities. J Immunother Cancer. 2025 May 19;13(5):e010570. doi: 10.1136/jitc-2024-010570.

  PMID: 40389376 DERIVED

• Jenner AL, Cassidy T, Belaid K, Bourgeois-Daigneault MC, Craig M. In silico trials predict that combination strategies for enhancing vesicular stomatitis oncolytic virus are determined by tumor aggressivity. J Immunother Cancer. 2021 Feb;9(2):e001387. doi: 10.1136/jitc-2020-001387.

  PMID: 33608375 DERIVED

• Pol JG, Acuna SA, Yadollahi B, Tang N, Stephenson KB, Atherton MJ, Hanwell D, El-Warrak A, Goldstein A, Moloo B, Turner PV, Lopez R, LaFrance S, Evelegh C, Denisova G, Parsons R, Millar J, Stoll G, Martin CG, Pomoransky J, Breitbach CJ, Bramson JL, Bell JC, Wan Y, Stojdl DF, Lichty BD, McCart JA. Preclinical evaluation of a MAGE-A3 vaccination utilizing the oncolytic Maraba virus currently in first-in-human trials. Oncoimmunology. 2018 Sep 19;8(1):e1512329. doi: 10.1080/2162402X.2018.1512329. eCollection 2019.

  PMID: 30546947 DERIVED

Study Officials

• Derek Jonker

  Ottawa Hospital Research Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2014
• First Posted: November 7, 2014
• Study Start: January 22, 2015
• Primary Completion: September 19, 2019
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)