VAXINIA + Pembrolizumab for Cancer

(MAST Trial)

Recruiting at 12 trial locations

Overseen By Lisa Guttman

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Imugene Limited

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Autoimmune disease, Transplant, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 21-42 days for initial dose evaluation

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with advanced or metastatic solid tumors. It aims to determine if CF33-hNIS, an experimental treatment, is safe and effective when administered directly into the tumor or through the bloodstream, either alone or with pembrolizumab (KEYTRUDA, an immunotherapy drug) or other chemotherapy drugs. Individuals who have tried at least two other cancer treatments without success might be suitable candidates, particularly if their tumors have spread and continue to grow. 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 treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking corticosteroids or other immunosuppressive medications at least 4 weeks before starting the study treatment. If you are on these medications, you will need to stop them to participate.

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

Research has shown that CF33-hNIS is well tolerated by patients. In previous studies, using CF33-hNIS alone was generally safe, with only mild side effects reported. The most common issues were minor, such as fatigue or mild fever, indicating that the treatment usually doesn't cause serious problems on its own.

When combined with pembrolizumab (a drug that helps the immune system fight cancer), CF33-hNIS increased the ability to kill tumors. However, no new major safety issues emerged with this combination. Patients handled it well, suggesting that adding pembrolizumab didn't cause severe side effects.

Overall, past results are promising for both CF33-hNIS alone and when used with pembrolizumab. However, it is important to remember that this is based on early research, and ongoing studies will provide more detailed safety information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CF33-hNIS in combination with Pembrolizumab because it introduces a novel approach to cancer treatment by using an oncolytic virus, CF33-hNIS, that specifically targets and destroys cancer cells while sparing healthy ones. Unlike traditional chemotherapy or radiation, which can harm both healthy and cancerous cells, this virus-based therapy aims to reduce side effects and improve precision in attacking tumors. Additionally, when combined with Pembrolizumab, a well-known immune checkpoint inhibitor, it potentially boosts the immune system’s ability to fight cancer more effectively. This innovative combination could lead to more effective and less toxic cancer treatments.

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

Research has shown that CF33-hNIS, a virus designed to target and kill cancer cells, holds promise for treating advanced cancers. In this trial, some participants will receive CF33-hNIS alone, while others will receive it with pembrolizumab, a drug that boosts the immune system. Studies have found that this virus, whether used alone or with pembrolizumab, is safe and may help shrink tumors. Early trials with CF33-hNIS showed positive results in cancers of the digestive system and bile ducts. Specifically, in some patients with advanced cancer, using it with pembrolizumab was linked to longer survival. Additionally, animal studies suggest that CF33-hNIS enhances the immune system's ability to fight cancer. These early findings indicate that CF33-hNIS could be an effective treatment option for certain advanced cancers. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

Adults with metastatic or advanced solid tumors who have tried at least two treatments can join this trial. They must be over 18, able to perform daily activities (ECOG 0-2), and have good kidney, liver, and blood function. People with active autoimmune diseases, poor heart or lung function, brain metastases that aren't controlled, recent radiotherapy or those on high-dose steroids or other immune-suppressing drugs cannot participate.

Inclusion Criteria

At least one measurable lesion

Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

My liver is working well.

Exclusion Criteria

I have not had radiotherapy in the last 2 weeks.

Active autoimmune disease

I have serious heart conditions, such as severe heart failure or uncontrolled high blood pressure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CF33-hNIS either intratumorally or intravenously, as monotherapy or in combination with pembrolizumab. Treatment occurs on Day 1 and 8 of Cycle 1, and then on Day 1 of each subsequent cycle.

21-42 days for initial dose evaluation

Multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment, including evaluation of adverse events and overall survival.

Up to 2 years

Open-label extension (optional)

Participants may continue to receive treatment and be monitored for long-term outcomes such as overall survival and disease control rate.

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• CF33-hNIS
• Pembrolizumab

Trial Overview The study is testing CF33-hNIS (an oncolytic virus) given directly into the tumor or through the vein as a single agent or combined with Pembrolizumab. It's an early-phase trial to see how safe these treatments are and what doses might work best for people with hard-to-treat cancers.

How Is the Trial Designed?

Group I: CF33-hNIS IV Administration in Combination with modified FOLFOX Experimental Treatment 2 Interventions

Group II: CF33-hNIS IV Administration in Combination with Pembrolizumab Experimental Treatment 2 Interventions

Group III: CF33-hNIS IV Administration Monotherapy Experimental Treatment 1 Intervention

Group IV: CF33-hNIS IT Administration in Combination with Pembrolizumab Experimental Treatment 2 Interventions

Group V: CF33-hNIS IT Administration Monotherapy Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Imugene Limited

Lead Sponsor

Trials

7

Recruited

340+

Published Research Related to This Trial

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a phase 1a/b trial involving 26 patients with PD-L1-positive non-small cell lung cancer (NSCLC), the combination of ramucirumab and pembrolizumab showed a manageable safety profile, with 84.6% experiencing treatment-related adverse events, primarily hypertension.

The treatment demonstrated promising efficacy, with an objective response rate of 42.3%, and particularly strong results in patients with high PD-L1 expression (TPS ≥ 50%), who had a median progression-free survival that was not reached.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 Expansion Cohort of Ramucirumab Plus Pembrolizumab in Advanced Treatment-Naive NSCLC. Herbst, RS., Arkenau, HT., Bendell, J., et al.[2023]

Combining pembrolizumab with trastuzumab and chemotherapy has been shown to reduce tumor size in patients, indicating enhanced efficacy of the treatment.

This combination therapy can also lead to complete responses in some patients, suggesting a potential for significant improvement in cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Addition Improves Clinical Response in HER2+ Gastric Cancer. [2022]

In a study of 38 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, the median overall survival was 11.08 months, indicating that the drug is a viable treatment option for this patient group.

The study found that while pembrolizumab's effectiveness in real-life settings appears lower than in clinical trials, it still provides significant benefits, particularly for patients with high PD-L1 expression, and highlights the importance of monitoring for immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world efficacy and safety of pembrolizumab in patients with non-small cell lung cancer: a retrospective observational study. Cavaille, F., Peretti, M., Garcia, ME., et al.[2022]

Pembrolizumab significantly improved progression-free survival (PFS) in patients with unresectable or metastatic microsatellite instability-high (MSI-H) colorectal cancer, with a median PFS of 16.5 months compared to 8.2 months for standard chemotherapy, indicating its efficacy as a first-line treatment.

The FDA found no safety concerns during the approval process, and while both pembrolizumab and standard of care had similar adverse reactions, the duration of treatment with pembrolizumab was nearly double that of standard care, suggesting a potentially more favorable treatment profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the First-line Treatment of Patients with MSI-H/dMMR Advanced Unresectable or Metastatic Colorectal Carcinoma. Casak, SJ., Marcus, L., Fashoyin-Aje, L., et al.[2022]

Pembrolizumab (Keytruda) has been approved by the FDA for treating high-risk, non-muscle invasive bladder cancer (NMIBC) in patients who are unresponsive to BCG therapy and are either ineligible for or have opted not to undergo cystectomy.

This approval specifically targets patients with carcinoma in situ (CIS) with or without papillary tumors, highlighting its role as a treatment option for those with limited surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. Wright, KM.[2021]

The study evaluated the effectiveness of pembrolizumab and cetuximab, both alone and in combination, on head and neck squamous cell carcinoma (HNSCC) using the FLAVINO assay, revealing significant variability in patient responses, particularly in those with cisplatin-resistant cases.

An 'IP-10 score' was developed to predict patient outcomes based on their response to treatment, indicating that higher levels of IP-10 release in response to interferon gamma (IFN-γ) stimulation may correlate with better outcomes for certain HNSCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine Profiles of Head and Neck Squamous Cell Carcinoma Undergoing Dual Immunotherapy With Cetuximab and Pembrolizumab Identify Interferon Gamma-Induced Protein 10 as Novel Biomarker. Berszin, M., Michaelides, I., Siemert, J., et al.[2022]

A 70-year-old woman developed immune checkpoint inhibitor (ICI)-related myocarditis and new-onset myasthenia gravis (MG) after starting pembrolizumab for metastatic thymic cancer, highlighting potential serious side effects of this treatment.

Despite the adverse effects, the patient showed significant improvement in her metastatic disease after 6 weeks, indicating that pembrolizumab can be effective in reducing tumor burden even in the presence of severe immune-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Checkpoint inhibitor-induced myocarditis and myasthenia gravis in a recurrent/metastatic thymic carcinoma patient: a case report. Szuchan, C., Elson, L., Alley, E., et al.[2022]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

In patients with hormone receptor-positive metastatic breast cancer, higher levels of specific immune cells (effector memory CD8+ and CD4+ T cells) before treatment were associated with better responses to the combination therapy of palbociclib, pembrolizumab, and letrozole, compared to those receiving only pembrolizumab and letrozole.

The combination therapy also led to significant changes in myeloid cell composition, including increased mature dendritic cells and decreased classical monocytes, which may enhance the immune response against the cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-existing effector T-cell levels and augmented myeloid cell composition denote response to CDK4/6 inhibitor palbociclib and pembrolizumab in hormone receptor-positive metastatic breast cancer. Egelston, C., Guo, W., Yost, S., et al.[2021]

In a phase II trial involving 50 patients with early triple-negative breast cancer, 66% achieved a pathological complete response (pCR) after treatment with nab-paclitaxel and pembrolizumab, indicating a promising efficacy of this combination therapy.

The treatment was associated with manageable side effects, with fatigue, peripheral sensory neuropathy, and neutropenia being the most common adverse events, suggesting that this regimen could be a viable alternative to platinum-based chemotherapy for patients who cannot tolerate it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in combination with nab-paclitaxel for the treatment of patients with early-stage triple-negative breast cancer - A single-arm phase II trial (NeoImmunoboost, AGO-B-041). Fasching, PA., Hein, A., Kolberg, HC., et al.[2023]

In a phase 1b study involving 28 patients with myelodysplastic syndromes (MDS) resistant to hypomethylating agents, pembrolizumab demonstrated manageable safety, with 36% experiencing treatment-related adverse events, but no patients achieved a complete or partial response.

Despite the lack of significant tumor response, 19% of patients showed a complete response in bone marrow, and the median overall survival was 6 months, indicating some clinical activity in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for myelodysplastic syndromes after failure of hypomethylating agents in the phase 1b KEYNOTE-013 study. Garcia-Manero, G., Ribrag, V., Zhang, Y., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.749

Oncolytic virus CF33-hNIS monotherapy for the treatment ... Results: As of Aug 2023, we report early results from seven patients with GI malignancies who received CF33-hNIS alone, including: colorectal ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05346484

NCT05346484 | A Study of CF33-hNIS (VAXINIA), an ... This is an open-label, dose-escalation, multi-center phase I study evaluating the safety of CF33-hNIS (hNIS - human sodium iodide symporter) administered ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S075333222500602X

CF33-hNIS-antiPDL1 enhances immunogenicity and anti ... Intraperitoneal CF33-hNIS-antiPDL1 increased antitumor immunity, reduced tumor burden, and prolonged survival in these mice. •. The results provide a ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10640805/

CF33-hNIS-anti-PD-L1 oncolytic virus followed by ... A significant reduction in cancer antigen 15-3 (CA 15-3) was documented over the course of treatment (Figure 2). Patient remained disease-free ...

5. imugene.com imugene.com/wp-content/uploads/2024/11/IMU6080_FA_Newsletter_MAY24_WEB.pdf

PHASE 1 CF33-HNIS STUDY UPDATE The trial, which uses the CF33-hNIS (VAXINIA) virus, demonstrated encouraging outcomes in patients with cholangiocarcinoma. This expansion study, now open for ...

6. jitc.bmj.com jitc.bmj.com/content/11/Suppl_1/A825

730 A phase I safety and tolerability study of VAXinia ... The combination of CF33-hNIS + anti-PD-L1 therapy showed a synergistic tumor killing, and increased survival in a preclinical triple negative ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12417592/

hNIS-based imaging to monitor treatment with the novel ... CF33-hNIS-antiPDL1 treatment and safety data. Nine patients received at least one dose of IT CF33-hNIS-antiPDL1 for mTNBC at one of the first three doses ...

8. onclive.com onclive.com/view/fda-grants-orphan-drug-designation-to-cf33-hnis-for-cholangiocarcinoma

FDA Grants Orphan Drug Designation to CF33-hNIS for ... Previously reported safety data showed that CF33-hNIS monotherapy was well tolerated, and the most common treatment-related adverse effects ...