GMCI + Immunotherapy for Lung Cancer

Not currently recruiting at 13 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Candel Therapeutics, Inc.

Must be taking: Immune checkpoint inhibitors

Must not be taking: DMARDs, Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disease, Heart disease, HIV, others

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 aims to test a new treatment called CAN-2409 for individuals with advanced lung cancer who aren't responding well to their current immunotherapy. CAN-2409 is a viral therapy designed to enhance the body's immune response to attack cancer cells more effectively. The trial seeks patients with stage III or IV non-small cell lung cancer who have stable disease or worsening symptoms despite ongoing immunotherapy. Participants should be able to continue their current treatment and have a tumor that can be safely injected with the new therapy. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial does not specify if you need to stop taking your current medications, but it does exclude those who need ongoing treatment with certain immune-related drugs or high doses of steroids. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that CAN-2409 has been tested in over 1,000 patients in clinical trials and is generally well-tolerated. Patients have reported no major safety issues, indicating it is safe for human use. This treatment uses a virus to help the immune system fight cancer by increasing the number of cells that attack tumors. It has shown promising results in patients with lung cancer who did not fully respond to other treatments. While the treatment appears safe, discussing any concerns with a healthcare provider before joining a trial is always important. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for lung cancer?

Unlike the standard treatments for lung cancer, which often include chemotherapy, radiation, and immune checkpoint inhibitors, CAN-2409 offers a novel approach by using gene-mediated cytotoxic immunotherapy (GMCI). This innovative treatment works by introducing a specific gene into cancer cells, making them more visible to the immune system, which then targets and destroys them. Researchers are excited about CAN-2409 because it enhances the body's natural defenses to specifically attack cancer cells, potentially leading to fewer side effects and improved effectiveness compared to traditional therapies. Additionally, it might provide new hope for patients whose cancer has not responded to existing immunotherapies.

What evidence suggests that CAN-2409 might be an effective treatment for lung cancer?

Studies have shown that CAN-2409 can benefit patients with non-small cell lung cancer (NSCLC) who did not respond well to certain immune treatments. In a previous study, patients resistant to these treatments lived for a median of 24.5 months when they received CAN-2409. This trial will evaluate CAN-2409 in different cohorts based on disease progression and response to prior immune checkpoint inhibitor (ICI) treatments. CAN-2409 increases the number of T-cells, which are immune cells that attack the tumor, and raises PD-L1 levels, making the cancer more detectable to the immune system. Overall, research suggests that adding CAN-2409 to current treatments could improve survival and help manage lung cancer more effectively. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults with Stage III/IV NSCLC who are not responding well to first-line immune checkpoint inhibitors. Participants must have stable organ function, no severe illnesses that could interfere with the study, and cannot be pregnant or planning pregnancy. They should not have had significant treatment interruptions or received certain other cancer treatments recently.

Inclusion Criteria

My blood clotting tests are within safe ranges for an injection procedure.

Your liver enzyme levels are not more than 5 times the upper limit of normal, and if they are higher, it doesn't affect your health in a significant way that would stop you from taking the study medication.

I have a tumor that can be measured and is suitable for injection.

Exclusion Criteria

I have no other cancer needing treatment except for skin cancer.

My tumor is pressing on nerves or blood vessels, posing a risk.

My brain cancer has not responded to treatment, as determined by my doctor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CAN-2409 plus prodrug in combination with standard of care immune checkpoint inhibitors

12 weeks

Regular visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Periodic visits for survival and progression assessments

Biomarker Studies

Blood and tumor samples are evaluated for changes in immune response before and after CAN-2409 + prodrug

6 months

What Are the Treatments Tested in This Trial?

Interventions

• CAN-2409

Trial Overview The trial tests CAN-2409 plus a prodrug alongside standard immune checkpoint inhibitors in patients whose cancers haven't responded adequately to initial treatments. The goal is to see if this combination can improve outcomes by boosting the body's immune response against cancer cells.

How Is the Trial Designed?

Group I: Cohorts Experimental Treatment 1 Intervention

Cohort 1A and 1B - persistent but stable disease at least 18 weeks after starting ICI treatment Cohort 2A and 2B - radiographic progressive disease at least 18 weeks after starting ICI treatment Cohort 3 - refractory disease defined as progressed by imaging at least 9 weeks after starting ICI treatment (CLOSED TO ENROLLMENT)

Who Is Running the Clinical Trial?

Candel Therapeutics, Inc.

Lead Sponsor

Trials

12

Recruited

1,300+

NYU Langone Health

Collaborator

Trials

1,431

Recruited

838,000+

Published Research Related to This Trial

Immune checkpoint inhibitors (ICIs) have significantly improved treatment outcomes for non-small cell lung cancer (NSCLC), offering durable benefits for some patients.

However, these therapies can lead to a range of immune-related adverse events (irAEs) that can affect multiple organ systems, highlighting the need for better understanding and prediction of these toxicities to improve patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitor-associated toxicity in advanced non-small cell lung cancer: An updated understanding of risk factors. Hu, X., Wang, L., Shang, B., et al.[2023]

In a study involving 15 patients with advanced non-small cell lung cancer (NSCLC) who had previously undergone chemotherapy, the novel antitumor agent MGI-114 showed no objective tumor responses, leading to the conclusion that it is not effective as a second-line treatment.

The treatment was associated with significant side effects, including grade 2 or higher thrombocytopenia in 40% of patients, and grade 3 nausea and grade 2 vomiting in 40% and 47% of patients, respectively, indicating safety concerns with this dosing regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of 6-hydroxymethylacylfulvene (MGI-114, irofulven) in patients with advanced non-small cell cancer previously treated with chemotherapy. Dowell, JE., Johnson, DH., Rogers, JS., et al.[2019]

Immunotherapy, particularly with antibodies that block immune checkpoints, has shown promise in treating non-small-cell lung cancer (NSCLC), which is a major cause of cancer-related deaths.

There is a growing interest in combining immunotherapy with chemotherapy to enhance treatment effectiveness by inducing immunogenic cell death, highlighting the need for further clinical trials in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lung cancer: potential targets for immunotherapy. Tartour, E., Zitvogel, L.[2014]

Citations

1. 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 ...

2. targetedonc.com targetedonc.com/view/can-2409-shows-strong-os-outcomes-in-ici-refractory-nsclc

CAN-2409 Shows Strong OS Outcomes in ICI-Refractory ... Final phase 2a results showed that CAN-2409 led to a median overall survival of 24.5 months in immune checkpoint inhibitor–refractory patients with NSCLC.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.8634

Overall survival after treatment with CAN-2409 plus ... Results: As of 16Jan2024, 73 patients were treated (safety population: ≥1 dose of CAN-2409) and 44 were evaluable per protocol (received 2 doses ...

4. 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 ... The Company's phase 3 clinical trial met its primary endpoint and secondary endpoints and demonstrated statistically significant improvement in DFS.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04495153

Study Details | NCT04495153 | CAN-2409 Plus Prodrug ... A combination of CAN-2409 added to standard of care (SOC) checkpoint inhibitors may lead to improved long-term outcomes for patients with NSCLC who have ...

6. ir.candeltx.com ir.candeltx.com/news-releases/news-release-details/candel-therapeutics-reports-both-prolonged-median-overall

Release Details Experimental treatment with CAN-2409 was associated with a median overall survival (mOS) of 24.5 months in patients with advanced NSCLC who ...