CAN-2409 + Chemoradiation/SBRT for Pancreatic Cancer

(PaTK02 Trial)

Not currently recruiting at 7 trial locations

Overseen By Andrea Manzanera, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Candel Therapeutics, Inc.

Must not be taking: Corticosteroids, Immunomodulators, Immunosuppressives

Disqualifiers: Hepatic dysfunction, Pancreatitis, Ascites, HIV, others

Stay on Your Current Meds You can continue your current medications while participating

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with a specific form of pancreatic cancer that might be removable with surgery. The researchers aim to determine if adding a new drug, CAN-2409 (also known as aglatimagene besadenovec), to standard treatments like chemotherapy and radiation is safe and effective. The trial compares this new approach to usual care to assess its efficacy. Individuals who have undergone treatment for pancreatic cancer with a specific type of chemotherapy and are now considering surgery might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on systemic corticosteroids, immunomodulators, or immunosuppressive drugs.

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

Research has shown that CAN-2409, when combined with a medication like valacyclovir or acyclovir, has been tested in other studies for safety. These studies found no unexpected safety issues, indicating that the treatment is generally well-tolerated. Specifically, one study found that after 36 months, no new side effects appeared, which reassures potential participants.

The treatment has also shown promising effectiveness, often aligning with safety data. Additionally, CAN-2409 has received FDA Orphan Drug Designation for pancreatic cancer, indicating potential benefits and safety in treating serious conditions.

Overall, existing data suggests that people have tolerated CAN-2409 with a prodrug well in past studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CAN-2409 combined with chemoradiation or stereotactic body radiation therapy (SBRT) for pancreatic cancer because it uses a unique mechanism to enhance the body's ability to fight cancer. Unlike traditional treatments that directly target cancer cells, CAN-2409 involves a gene therapy approach where a virus helps deliver a specific gene into the cancer cells, making them more susceptible to destruction when a prodrug like valacyclovir or acyclovir is administered. This approach has the potential to improve the effectiveness of existing treatments by making the cancer cells more vulnerable to radiation and chemotherapy, potentially leading to better outcomes for patients.

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

In this trial, participants in the test arm will receive CAN-2409 combined with a prodrug like valacyclovir, alongside neoadjuvant chemoradiation or SBRT, followed by surgery. Studies have shown that CAN-2409, when paired with a drug like valacyclovir, can significantly benefit patients with pancreatic cancer. Specifically, previous studies reported a 30% increase in the time patients lived without cancer recurrence. Additionally, research found that 71.4% of patients treated with CAN-2409 were still alive after two years, compared to only 16.7% in a group that did not receive the treatment. This treatment strengthens the body's immune system to fight cancer cells more effectively. These findings suggest that CAN-2409 could be a powerful tool against pancreatic cancer. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults over 18 with borderline resectable pancreatic cancer, who've had FOLFIRINOX chemotherapy for at least 4 months and are healthy enough for major surgery. They should have no distant metastasis or lymph node involvement outside the planned surgery area, and their tumor must be accessible for injection. Key health metrics like liver function, kidney clearance, blood cell counts need to be within specific ranges.

Inclusion Criteria

My cancer is near the liver artery but hasn't reached the main stomach artery.

My tumor can be reached for treatment and might be removable after specific chemotherapy.

My cancer has not spread to distant areas or lymph nodes outside the surgery area.

Exclusion Criteria

I do not have any current cancer except for skin cancer.

Known sensitivity or allergic reactions to acyclovir or valacyclovir

Known to be HIV+

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Participants receive at least 4 months (8 cycles) of a FOLFIRINOX based induction therapy

16 weeks

Treatment

Participants receive three courses of CAN-2409 + prodrug, with the first course starting prior to CR or SBRT, the second course concurrent with CR or just following completion of SBRT, and the third at time of resection

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Long-term Follow-up

Participants are followed for disease-free survival and overall survival

60 months

What Are the Treatments Tested in This Trial?

Interventions

• Aglatimagene besadenovec
• Chemoradiation
• GMCI (aglatimagene besadenovec + valacyclovir)
• Stereotactic body radiation therapy

Trial Overview

The trial is testing CAN-2409 plus a prodrug (valacyclovir or acyclovir) in patients undergoing neoadjuvant chemoradiation (CR) or stereotactic body radiation therapy (SBRT), followed by surgery. The goal is to assess safety, effectiveness, and immune response compared to standard care.

How Is the Trial Designed?

Group I: Test Arm Experimental Treatment 4 Interventions

CAN-2409 + prodrug (valacylovir or acyclovir) in combination with neoadjuvant chemoradiation or SBRT + Surgery

Group II: Control Arm Active Control 3 Interventions

Neoadjuvant chemoradiation or SBRT + Surgery

Chemoradiation is already approved in China for the following indications:

Approved in China as Baizean for:

• Classical Hodgkin’s lymphoma (cHL)
• Locally advanced or metastatic urothelial carcinoma (UC)
• Locally advanced or metastatic non-small cell lung cancer (NSCLC)
• Advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors
• Locally advanced or metastatic esophageal squamous cell carcinoma (ESCC)
• Recurrent or metastatic nasopharyngeal cancer (NPC)

Who Is Running the Clinical Trial?

Candel Therapeutics, Inc.

Lead Sponsor

Trials

12

Recruited

1,300+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Ohio State University

Collaborator

Trials

891

Recruited

2,659,000+

Published Research Related to This Trial

Stereotactic body radiation therapy (SBRT) combined with chemotherapy for unresectable pancreatic cancer showed a median overall survival of 14.3 months and a local control rate of 79%, indicating its effectiveness in managing this challenging condition.

The treatment was generally well tolerated, with minimal acute toxicity, although there were some severe late toxicities, suggesting that while SBRT is a promising option, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiation Therapy (SBRT) Combined With Chemotherapy for Unresected Pancreatic Adenocarcinoma. Gurka, MK., Kim, C., He, AR., et al.[2022]

Stereotactic body radiation therapy (SBRT) is emerging as a promising treatment for pancreatic cancer (PCA), particularly for patients with locally advanced, unresectable disease, offering potentially better tumor control compared to traditional chemotherapy and chemoradiation.

Early studies of SBRT using multiple doses (3-5) have shown favorable outcomes with improved tumor control and manageable toxicity rates, suggesting it may be a viable alternative to current standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy in pancreatic cancer: the new frontier. Moningi, S., Marciscano, AE., Rosati, LM., et al.[2014]

Patients with unresectable pancreatic carcinoma have very low survival rates, with less than 5% overall survival at 5 years, even with standard treatments like chemotherapy and radiation.

Stereotactic body radiation therapy (SBRT) offers a promising alternative, delivering treatment in just 3-5 days with minimal disruption to chemotherapy, showing excellent local control and acceptable toxicity, suggesting it could improve patient outcomes and warrants further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiation Therapy (SBRT) for Unresectable Pancreatic Carcinoma. Stauder, MC., Miller, RC.[2021]

Stereotactic body radiation therapy (SBRT) for unresectable pancreatic cancer showed similar overall survival and disease control outcomes compared to conventional intensity modulated radiation therapy (IMRT), based on a retrospective review of 270 patients (44 SBRT and 226 IMRT).

SBRT was associated with significantly lower rates of acute gastrointestinal toxicity, fatigue, and hematologic toxicity compared to IMRT, indicating that SBRT may be a safer and more tolerable treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation vs. intensity-modulated radiation for unresectable pancreatic cancer. Park, JJ., Hajj, C., Reyngold, M., et al.[2022]

Stereotactic body radiation therapy (SBRT) shows promising efficacy for patients with locally advanced pancreatic cancer, with a pooled 1-year overall survival rate of 51.6% and a median overall survival of 17 months based on a systematic review of 19 studies involving 1009 patients.

The treatment also demonstrated a 1-year locoregional control rate of 72.3%, with severe adverse events occurring in less than 10% of patients, suggesting that SBRT is a safe and effective option for inoperable pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiation Therapy for Locally Advanced Pancreatic Cancer: A Systematic Review and Pooled Analysis of 19 Trials. Petrelli, F., Comito, T., Ghidini, A., et al.[2023]

Stereotactic body radiotherapy (SBRT) is an effective treatment for pancreatic cancer, showing good tolerance and disease control, and may become a standard treatment option alongside chemoradiotherapy (CRT).

The combination of SBRT with chemotherapy could enhance treatment effects, although optimal doses and fractionation schedules for SBRT have yet to be established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy in pancreatic adenocarcinoma. de la Pinta, C.[2023]

The use of neoadjuvant stereotactic body radiation therapy (SBRT) for pancreatic cancer is on the rise, increasing from 0% in 2004 to 9.5% in 2015, particularly in patients with more advanced disease.

Patients receiving neoadjuvant chemo-SBRT showed improved overall survival rates and higher rates of R0 resection compared to those receiving chemotherapy or conventional radiation therapy, suggesting that SBRT may offer significant benefits in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant stereotactic body radiation therapy for nonmetastatic pancreatic adenocarcinoma. Jiang, W., Haque, W., Verma, V., et al.[2023]

Citations

1.

ir.candeltx.com

ir.candeltx.com/news-releases/news-release-details/candel-therapeutics-presents-positive-phase-3-can-2409-results

Candel Therapeutics Presents Positive Phase 3 CAN-2409 ...

CAN-2409 induced 80.4% pathological complete responses in the two-year post-treatment biopsies compared to 63.6% observed in the control arm (p= ...

2.

ir.candeltx.com

ir.candeltx.com/news-releases/news-release-details/candel-therapeutics-presents-phase-3-clinical-trial-can-2409

Candel Therapeutics Presents Phase 3 Clinical Trial of ...

The trial achieved its primary endpoint with a 30% improvement in disease-free survival (HR 0.7, p=0.0155) and demonstrated a 38% improvement in ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02446093

Study Details | NCT02446093 | Neoadjuvant CAN-2409 in ...

The purpose of this study is to characterize the safety, preliminary efficacy, and immune biologic activity of CAN-2409 + prodrug (valacyclovir or ...

4.

onclive.com

onclive.com/view/can-2409-plus-valacyclovir-generates-positive-phase-2-survival-results-in-pdac

CAN-2409 Plus Valacyclovir Generates Positive Phase 2 ...

Positive phase 2 findings for CAN-2409 plus valacyclovir in pancreatic ductal adenocarcinoma have been reported.

5.

ir.candeltx.com

ir.candeltx.com/news-releases/news-release-details/candel-therapeutics-announces-positive-final-survival-data

Candel Therapeutics Announces Positive Final Survival ...

Previous analysis at 24 months showed survival rates of 71.4% in patients treated with CAN-2409 compared to 16.7% in the control group. Previous ...

6.

onclive.com

onclive.com/view/can-2409-granted-fda-orphan-drug-designation-in-pancreatic-cancer

CAN-2409 Receives FDA Orphan Drug Designation in ...

At a data cutoff of March 29, 2024, patients in the CAN-2409 arm (n = 7) achieved an estimated median overall survival (OS) of 28.8 months ...

7.

clin.larvol.com

clin.larvol.com/trial-detail/NCT02446093

Neoadjuvant CAN-2409 in Combination With ...

At 36 months, estimated survival was 47.6% in the CAN-2409 group versus 16.7% in the control group; No new safety signals were observed, providing further ...