Oncolytic Virus Therapy for Pancreatic Cancer

Not currently recruiting at 1 trial location

Overseen By Benjamin Musher, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Lokon Pharma AB

Must be taking: Gemcitabine, Nab-paclitaxel

Must not be taking: Corticosteroids, Immune inhibitors

Disqualifiers: Autoimmune disease, Hepatitis, HIV, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 707

Duration: 9 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for pancreatic cancer using a virus called LOAd703 (also known as Delolimogene Mupadenorepvec), designed to attack and kill cancer cells. The goal is to determine if this virus can be safely used alongside standard cancer treatments to shrink tumors and improve survival. Patients with pancreatic cancer who have tumors accessible for injections and are not eligible for full surgical removal may qualify for this trial. Participants will receive regular care with added injections of LOAd703, and some will also receive atezolizumab, a drug that helps the immune system fight cancer. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop all current medications. However, you cannot take high-dose corticosteroids, certain immune inhibitors, biologic therapies, investigational agents, or systemic immunostimulatory agents close to or during the trial. Check with the trial team about your specific medications.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but certain treatments like high-dose corticosteroids, immune inhibitors, and investigational agents are not allowed close to the start of the study. It's best to discuss your specific medications with the trial team.

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

Research has shown that LOAd703, a special virus designed to attack cancer cells, has been generally safe in past studies. This virus targets and kills only cancer cells, sparing healthy ones. In these studies, researchers used LOAd703 with standard chemotherapy for patients with pancreatic cancer. The results indicated that it was well-tolerated, with most patients not experiencing severe side effects. Some patients might develop a fever shortly after the virus is injected, a common reaction as the body responds to the treatment.

When combined with another drug called atezolizumab, LOAd703 was also well-tolerated. Some patients even experienced a period where their cancer stopped growing. These findings suggest that the treatment is safe for further testing, but it remains experimental and is not yet approved by the FDA. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for pancreatic cancer, which typically involve chemotherapy, radiation, or surgery, LOAd703 introduces a novel approach using oncolytic virus therapy. This treatment employs a virus engineered to selectively infect and kill cancer cells, while also boosting the body's immune response against the tumor. In one arm of the study, LOAd703 is combined with atezolizumab, an immune checkpoint inhibitor, to potentially enhance the immune system's ability to fight the cancer. Researchers are excited because this dual-action strategy could offer a more targeted and effective treatment option for pancreatic cancer, with the potential to improve outcomes compared to conventional therapies.

What evidence suggests that LOAd703 might be an effective treatment for pancreatic cancer?

Research has shown that LOAd703, a virus used to fight cancer, may help treat pancreatic cancer. In this trial, one group of participants will receive LOAd703 with chemotherapy, which studies have demonstrated to have significant cancer-fighting effects. Some patients experienced tumor shrinkage or had their cancer remain stable for extended periods. LOAd703 attacks cancer cells directly and enhances the immune system's ability to fight cancer. In another group, LOAd703 will be combined with the drug atezolizumab. This combination has been well-tolerated, and some patients have responded positively. While more research is needed, these early results offer promise for those considering this treatment. ^{1 2 3 6 7}

Who Is on the Research Team?

Angelica Loskog, PhD

Principal Investigator

Lokon Pharma AB

Are You a Good Fit for This Trial?

Adults diagnosed with pancreatic ductal adenocarcinoma, not eligible for surgery, can join this trial. They must be fit for standard chemotherapy and able to undergo sedation for injections. Women of childbearing age need a negative pregnancy test and must use contraception. Exclusions include pregnant or breastfeeding women, recent biologic therapy users, those with certain illnesses or high-dose steroid treatment, and individuals with other cancers within the last two years.

Inclusion Criteria

I am eligible for treatment with gemcitabine and nab-paclitaxel.

My cancer cannot be completely removed by surgery.

I am not pregnant and agree to use birth control during the study.

Exclusion Criteria

I am not on any treatments that could interfere with the study, such as high dose steroids or certain immune system targeting drugs.

I haven't taken strong immune system drugs like alemtuzumab or rapamycin in the last 3 weeks.

I have a noticeable amount of fluid in my abdomen.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive standard of care treatment with gemcitabine and nab-paclitaxel, and intratumoral injections of LOAd703 every other week for 6 doses, with an option for 6 additional doses if beneficial.

9 months

Biweekly visits for LOAd703 injections, additional visits for standard chemotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment, with blood samples and imaging to evaluate tumor size and health status.

3 months

Every 3 months

Extension

Participants may receive up to 6 additional doses of LOAd703 if they are benefiting from the treatment.

3 months

What Are the Treatments Tested in This Trial?

Interventions

• LOAd703

Trial Overview

The trial is testing LOAd703, an oncolytic virus modified to boost the immune system against cancer cells when injected into tumors. It's given alongside standard chemo drugs gemcitabine and nab-paclitaxel, with or without atezolizumab (an anti-cancer antibody). The goal is to shrink tumors and improve survival in pancreatic cancer patients.

How Is the Trial Designed?

Group I: Arm 2: Intratumoral LOAd703 + atezolizumab Experimental Treatment 4 Interventions

Patients will receive gemcitabine intravenously at a dose of 1000mg/m2 + nab-paclitaxel 125 mg/m2 as per hospital standards. One cycle will be one dose of gemcitabine +nab-paclitaxel given on days 1, 8, and 15 of a 28 day cycle. LOAd703 will be given every other week for 6 doses starting on day 15 of the first cycle of chemotherapy. There is an option for an additional 6 doses if patients benefit from treatment. A fixed dose of atezolizumab 1680 mg will be given every 4 weeks on day 1 of each chemotherapy cycle. Patients will be assigned to the following LOAd703 doses: Dose level 1: 1 X 10\^11 viral particles per treatment Dose level 2: 5 X 10\^11 viral particles per treatment

Group II: Arm 1 Intratumoral LOAd703 Experimental Treatment 3 Interventions

Patients will receive gemcitabine intravenously at a dose of 1000mg/m2 + nab-paclitaxel 125 mg/m2 as per hospital standards. One cycle will be one dose of gemcitabine +nab-paclitaxel given on days 1, 8, and 15 of a 28 day cycle. LOAd703 will be given every other week for 6 doses starting on day 15 of the first cycle of chemotherapy. There is an option for an additional 6 doses if patients benefit from treatment. The following LOAd703 doses will be evaluated: Dose level 1: 5 X 10\^10 viral particles per treatment Dose level 2: 1 X 10\^11 viral particles per treatment Dose level 3: 5 X 10\^11 viral particles per treatment

LOAd703 is already approved in United States for the following indications:

Approved in United States as LOAd703 for:

• None approved yet; received FDA Fast Track designation for pancreatic cancer

Who Is Running the Clinical Trial?

Lokon Pharma AB

Lead Sponsor

Trials

3

Recruited

120+

Published Research Related to This Trial

Nanoliposomal irinotecan combined with 5-fluorouracil/folinic acid has been approved as the first second-line treatment for metastatic pancreatic cancer, showing significant improvements in progression-free survival (3.1 months vs. 1.5 months) and overall survival (6.2 months vs. 4.1 months) compared to 5-FU/folinic acid alone.

Patients receiving this combination therapy may experience more frequent adverse effects like neutropenia, fatigue, and diarrhea, necessitating careful monitoring and potential dose adjustments, especially for those with specific UGT1A1 gene variants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on the role of nanoliposomal irinotecan in the treatment of metastatic pancreatic cancer. Rahman, FAU., Ali, S., Saif, MW.[2020]

In a small clinical study involving 3 patients with stage IV pancreatic cancer, the gene therapy Rexin-G successfully arrested tumor growth in all participants without causing dose-limiting toxicity or significant side effects.

Two of the patients remained alive with stable disease for 5 and 14 months post-diagnosis, indicating potential efficacy of Rexin-G as a treatment option, which will inform future phase I/II clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First clinical experience using a 'pathotropic' injectable retroviral vector (Rexin-G) as intervention for stage IV pancreatic cancer. Gordon, EM., Cornelio, GH., Lorenzo, CC., et al.[2022]

Recent phase I trials have shown that several novel treatments for pancreatic adenocarcinoma, including a MEK inhibitor and a connective tissue growth factor inhibitor, are safe for patients.

These promising treatments, along with others tested, will undergo phase II trials to determine their potential effectiveness in treating this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel agents in the management of pancreatic adenocarcinoma: phase I studies. Highlights from the "2011 ASCO Gastrointestinal Cancers Symposium". San Francisco, CA, USA. January 20-22, 2011. Dimou, AT., Syrigos, KN., Saif, MW.[2022]

In a phase II study involving 44 patients with gemcitabine-refractory pancreatic cancer, FOLFOX4 demonstrated an objective response rate of 11.4% and a tumor stabilization rate of 40.9%, indicating its potential efficacy as a rescue therapy.

FOLFOX4 was generally well-tolerated, but significant hematologic toxicities were observed, including grade 3 or 4 neutropenia in 43.2% of patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Folfox4 as a rescue chemotherapy for gemcitabine-refractory pancreatic cancer. Chung, JW., Jang, HW., Chung, MJ., et al.[2022]

Recent studies highlight that pancreatic adenocarcinoma, known for its aggressive nature and poor prognosis, may benefit from immunotherapeutic and oncolytic viral strategies that enhance the immune response against tumors.

Preclinical and early clinical results show promising antitumor efficacy for these novel therapies, suggesting they could improve treatment outcomes and deepen our understanding of pancreatic cancer biology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapeutic and oncolytic viral therapeutic strategies in pancreatic cancer. Khan, ML., Halfdanarson, TR., Borad, MJ.[2023]

Targeted therapies and chemotherapies for pancreatic cancer have had limited success in improving long-term survival rates, with 5-year survival remaining unchanged.

Oncolytic viral therapy, which uses self-replicating nanoparticles, is emerging as a promising new approach for treating pancreatic cancer, leveraging the latest insights into the disease's genetic and molecular mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncolytic viral therapy for pancreatic cancer: current research and future directions. Ady, JW., Heffner, J., Klein, E., et al.[2020]

Oncolytic virus therapy, particularly using the adenovirus ONYX-015, showed promising results in a phase II clinical trial for pancreatic cancer, with about 50% of patients experiencing tumor reduction or stabilization.

Recent advancements have made oncolytic viruses more effective by targeting tumor-specific environments and enhancing the immune response against cancer cells, suggesting that this therapy could be a viable option for treating pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of oncolytic virus therapy for pancreatic cancer. Kasuya, H., Takeda, S., Nomoto, S., et al.[2022]

Oncolytic virotherapy shows promise as a potential treatment for pancreatic ductal adenocarcinoma (PDAC), a highly aggressive cancer, by specifically targeting and destroying tumor cells while also stimulating the immune response.

The pancreatic tumor microenvironment presents significant challenges for treatment, including immunosuppression and limited drug access, making oncolytic viruses particularly suitable for combination therapies aimed at overcoming these barriers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncolytic virotherapy for pancreatic ductal adenocarcinoma: A glimmer of hope after years of disappointment? Tassone, E., Muscolini, M., van Montfoort, N., et al.[2021]

Oncolytic viruses (OVs) like adenoviruses, herpesviruses, and reoviruses have been extensively studied and are currently in clinical trials as potential treatments for pancreatic cancer, showing promise in targeting this difficult-to-treat disease.

The review highlights the unique biological characteristics of these viruses and suggests that genetic manipulation or combination with other therapies could enhance their effectiveness against pancreatic cancer, leveraging insights from recent studies on the disease's molecular biology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncolytic virotherapy for pancreatic cancer. Wennier, S., Li, S., McFadden, G.[2022]

FG-3019, which inhibits connective tissue growth factor, was found to be relatively safe in a phase I study, indicating potential for further development in treating pancreatic adenocarcinoma.

ASG-5ME, an antibody targeting SLC44A4 in pancreatic cancer, also demonstrated safety in a phase I trial, suggesting it could be a promising treatment option, while tanespimycin showed no effectiveness in a phase II study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel agents in the treatment of pancreatic adenocarcinoma. Dimou, A., Syrigos, KN., Saif, MW.[2020]

Combining the oncolytic virus H-1PV with gemcitabine in pancreatic cancer treatment showed synergistic effects, allowing for a significant reduction in the effective dose of gemcitabine by up to 15-fold, even in drug-resistant cancer cells.

H-1PV demonstrated an excellent safety profile and, when used as a second-line treatment after gemcitabine, resulted in reduced tumor growth, prolonged survival, and no metastases in animal models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement of gemcitabine-based therapy of pancreatic carcinoma by means of oncolytic parvovirus H-1PV. Angelova, AL., Aprahamian, M., Grekova, SP., et al.[2022]

Adipose-derived stem cells (ADSCs) infected with the recombinant myxoma virus (MYXV) can effectively target pancreatic ductal adenocarcinoma (PDAC) without significantly harming the ADSCs, while rapidly killing cancer cells.

Administering ADSC/MYXV via the intraperitoneal route enhances the virus's distribution to the pancreas, leading to reduced tumor burden and improved survival in mice with PDAC, along with a stronger adaptive immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myxoma Virus Expressing LIGHT (TNFSF14) Pre-Loaded into Adipose-Derived Mesenchymal Stem Cells Is Effective Treatment for Murine Pancreatic Adenocarcinoma. Jazowiecka-Rakus, J., Hadrys, A., Rahman, MM., et al.[2023]

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LOAd703 Oncolytic Virus Therapy for Pancreatic Cancer

The purpose of this study is to see if LOAd703 (an oncolytic adenovirus) can be safely given to patients with pancreatic cancer.

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A phase I/II clinical trial

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