Viral Therapy for Cancer

Not currently recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Canadian Cancer Trials Group

Must not be taking: Antivirals, Steroids, Immunosuppressants

Disqualifiers: Other malignancies, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new viral therapy that could treat certain types of cancer by using viruses to target and kill cancer cells, potentially shrinking tumors and boosting the immune system's response. The study tests two experimental treatments, AdMA3 and MG1MA3, in different combinations to determine which works best. It seeks participants with advanced solid tumors that express a specific protein (MAGE-A3) and for whom standard treatments aren't effective. Those with non-small cell lung cancer, breast cancer, or certain types of esophageal cancer with these characteristics might find this trial suitable. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) before starting the treatment. This means you may need to stop taking some of your current medications, especially anti-viral, anti-platelet, or anti-coagulation medications, at least 14 days before enrolling in the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the AdMA3 and MG1MA3 viruses have potential in early studies. These viruses target and kill cancer cells while sparing healthy cells. Studies have found that AdMA3, used alone or with MG1MA3, can activate the body’s immune system to combat cancer cells.

In other studies, MG1MA3 has been safely used in patients with various types of cancer, causing few side effects, which are usually mild. For example, some patients have experienced flu-like symptoms, common with many immune-boosting treatments.

The combination of AdMA3 and MG1MA3 has also been tested and can be administered without major safety concerns. Researchers tested different doses to find the safest and most effective amount. The results were promising, with no major safety issues reported.

While the treatment is still under investigation, current data suggest that both AdMA3 and MG1MA3 are generally well-tolerated, meaning they do not cause severe side effects in most patients. However, as with any trial, risks exist, and discussing these with a healthcare provider before joining any study is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the viral therapies AdMA3 and MG1MA3 for cancer because they employ a unique mechanism of action that is different from traditional treatments like chemotherapy and radiation. AdMA3 acts as a viral vaccine that primes the immune system to recognize and attack cancer cells. When used in combination with MG1MA3, which serves as a boost, this approach has the potential to enhance the immune response even further. Unlike conventional treatments that often have broad, systemic effects, these therapies specifically target cancer cells, which could lead to fewer side effects. The innovative use of viruses to stimulate the body's own defenses offers a promising new avenue in cancer treatment.

What evidence suggests that this trial's treatments could be effective for cancer?

Research has shown that the viruses AdMA3 and MG1MA3 may help fight cancer by shrinking tumors, killing cancer cells, and boosting the immune system. In this trial, participants will be divided into different treatment arms to evaluate these therapies. Participants in Arm B will receive the AdMA3 virus, which acts like a vaccine, preparing the body to defend itself. Meanwhile, Arm A participants will receive MG1MA3 alone, which strengthens this defense. In Arm C, participants will receive both AdMA3 and MG1MA3 together. Studies have found that this combination can create strong immune responses against tumors. Some patients have experienced significant tumor shrinkage, and similar results have been observed in animal studies. This suggests that these treatments could effectively target cancer cells. ^{1 2 6 7 8}

Who Is on the Research Team?

Derek Jonker

Principal Investigator

Ottawa Hospital Research Institute

Are You a Good Fit for This Trial?

Adults with certain advanced solid tumors expressing MAGE-A3, who've had at least one standard treatment. They must have measurable disease and be in good physical condition (ECOG 0 or 1). Excluded are those with active infections, other cancers needing treatment, significant medical issues, brain metastases requiring steroids, or pregnant/breastfeeding individuals.

Inclusion Criteria

My cancer is advanced, cannot be surgically removed, and tests positive for MAGE-A3.

My cancer is advanced, cannot be surgically removed, and tests positive for MAGE-A3.

Exclusion Criteria

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, Anyone with significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication (e.g. systemic corticosteroids), Use of anti-viral medication, steroids, immunosuppressive agents (cyclosporine, interferon) or immunization (including the flu shot) within 14 days prior to registration. Use of anti-viral, anti-platelet, or anti-coagulation medication that cannot be discontinued within 14 days of enrollment, Patients with disease/tumour invading a major vascular structure (e.g. carotid artery), tumour related impending bowel obstruction or clinically significant and/or rapidly accumulating ascites, pericardial or pleural effusions, Patients with conditions likely to have resulted in splenic dysfunction (e.g. splenectomy, sickle cell anemia, radiation to the spleen ≥ 20Gy, congenital asplenism), Patients with ≥ grade 2 dyspnea and/or requirement for supplemental oxygen. Patients with important pulmonary disease must complete a 6 minute ambulation test with O2 states ≥ 90% to be eligible

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Participants receive MG1MA3 alone or in combination with AdMA3 to determine the maximum feasible dose and safety profile

8 weeks

Multiple visits for dose administration and monitoring

Phase II Treatment

Participants receive treatment to evaluate objective tumour response rate using RECIST v1.1

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• AdMA3
• MG1MA3

Trial Overview The trial is testing two viruses: MG1MA3 alone or followed by AdMA3. These have shown promise in killing cancer cells and boosting immune response against the tumor antigen they carry. The study aims to see if this approach works better than standard treatments.

How Is the Trial Designed?

Group I: Arm C- AdMA3 plus MG1MA3 (prime + boost) Experimental Treatment 2 Interventions

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.

Group II: Arm B- AdMA3 (vaccine prime) alone Experimental Treatment 1 Intervention

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

Group III: Arm A (MG1MA3 virus alone) Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Ottawa Hospital Research Institute

Collaborator

Trials

585

Recruited

3,283,000+

Published Research Related to This Trial

In a phase I trial involving 41 patients with recurrent glioblastoma (rGBM), the oncolytic herpes virus CAN-3110 was safely administered without dose-limiting toxicities, showing potential for preferential tumor replication due to its unique genetic modifications.

Patients with pre-existing HSV1 antibodies experienced improved survival and tumor response, suggesting that CAN-3110 can enhance immune responses against tumors even in challenging microenvironments, providing a promising avenue for treating cancers resistant to traditional immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trial links oncolytic immunoactivation to survival in glioblastoma. Ling, AL., Solomon, IH., Landivar, AM., et al.[2023]

In a pilot study involving 21 patients with advanced melanoma resistant to anti-PD-1 therapy, the combination of ONCOS-102 (an oncolytic adenovirus) and pembrolizumab was well tolerated, with most side effects being mild to moderate, such as fever and chills.

The treatment resulted in an objective response rate of 35%, with 53% of patients showing a reduction in size of non-injected tumors, indicating a systemic immune response and suggesting that ONCOS-102 effectively enhances T-cell infiltration and activity against melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study of ONCOS-102 and Pembrolizumab: Remodeling of the Tumor Microenvironment and Clinical Outcomes in Anti-PD-1-Resistant Advanced Melanoma. Shoushtari, AN., Olszanski, AJ., Nyakas, M., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11669620/

Cancer vaccines: an update on recent achievements and ... Some clinical trials using mRNA-based cancer vaccines have demonstrated promising results. A phase I study using an RNA-LPX vaccine ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2017.35.15_suppl.e14637

Phase I study of oncolytic virus (OV) MG1 maraba/MAGE- ... MG1MA3, both alone and after immune priming with a MAGE-A3 modified adenovirus (AdMA3) may trigger anti-tumour T-cell responses. Methods: N = 41 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02285816

Study Details | NCT02285816 | MG1 Maraba/MAGE-A3 ... 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 ...

4. mdpi.com mdpi.com/2072-6694/16/19/3428

Innovative Cancer Immunotherapy with MAGE-A3 mRNA ... Immunization with this vaccine significantly inhibited tumor growth in mice and activated strong immune responses. This suggests that the MAGE- ...

5. researchgate.net researchgate.net/publication/344978492_Phase_I_study_of_oncolytic_virus_OV_MG1_marabaMAGE-A3_MG1MA3_with_and_without_transgenic_MAGE-A3_adenovirus_vaccine_AdMA3_in_incurable_advancedmetastatic_MAGE-A3-expressing_solid_tumours_CCTG_IND214

Phase I study of oncolytic virus (OV) MG1 maraba/MAGE ... In this study, we report that systemic delivery of CARG-2020 via the intravenous (i.v.) route can successfully control CRC growth. To further ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11475142/

Innovative Cancer Immunotherapy with MAGE-A3 mRNA ... This study investigated advanced immunotherapy strategies, focusing on mRNA vaccines that target tumor-specific antigens to activate the immune system.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6263248/

Development and applications of oncolytic Maraba virus ... Maraba virus-vectored cancer vaccines represent a safe and novel therapeutic option for cats. ... (AdMA3) in incurable advanced/metastatic ...

8. aacrjournals.org aacrjournals.org/clincancerres/article/27/3/689/83407/The-Changing-Landscape-of-Therapeutic-Cancer

The Changing Landscape of Therapeutic Cancer Vaccines ... Advantages include simplicity, ease of manufacture, and safety; however, naked DNA vaccines have limited efficacy as a result of low transfection rates into ...