GMCI + Immunotherapy for Lung Cancer

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

90 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this clinical trial is to evaluate the effects of adding CAN-2409 + prodrug for stage III/IV NSCLC patients who are on standard of care first line immune checkpoint inhibitor (ICI) treatment with evidence that the clinical response is inadequate. CAN-2409 is a viral immunotherapy approach that induces tumor-infiltrating T-cells and a consequent PD-L1 up-regulation. 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 suboptimal response to ICI therapy.

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.

What data supports the effectiveness of the treatment CAN-2409 in the GMCI + Immunotherapy for Lung Cancer trial?

Research shows that GMCI, which includes the treatment CAN-2409, is safe and can activate immune cells in lung cancer patients, potentially enhancing the effects of other immune therapies. In a study, patients with lung cancer who received GMCI showed increased immune cell activity, suggesting it could be beneficial when combined with other treatments. ^{1 2 3 4 5}

Is GMCI + Immunotherapy safe for humans?

The safety of GMCI + Immunotherapy, also known as CAN-2409, has been studied in various conditions. While immune checkpoint inhibitors used in immunotherapy can cause side effects called immune-related adverse events (irAEs), these can range from mild to severe and affect different body systems. It's important to discuss potential risks with your healthcare provider. ^{6 7 8 9 10}

How does GMCI + Immunotherapy differ from other lung cancer treatments?

GMCI + Immunotherapy is unique because it combines gene immunotherapy, which enhances the immune system's ability to recognize and attack cancer cells, with other immune-stimulating products that activate specific immune processes. This approach aims to improve survival and response in patients with non-small cell lung cancer (NSCLC) by leveraging the body's own immune system, unlike traditional chemotherapy that directly targets cancer cells. ^{5 11 12 13 14}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase I study of gene-mediated cytotoxic immunotherapy with AdV-tk as adjuvant to surgery and radiation for pediatric malignant glioma and recurrent ependymoma. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Preclinical investigation of combined gene-mediated cytotoxic immunotherapy and immune checkpoint blockade in glioblastoma. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Neoadjuvant Gene-Mediated Cytotoxic Immunotherapy for Non-Small-Cell Lung Cancer: Safety and Immunologic Activity. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Phase I Study of Intrapleural Gene-Mediated Cytotoxic Immunotherapy in Patients with Malignant Pleural Effusion. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

Icariside II potentiates the anti-PD-1 antitumor effect by reducing chemotactic infiltration of myeloid-derived suppressor cells into the tumor microenvironment via ROS-mediated inactivation of the SRC/ERK/STAT3 signaling pathways. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Prognostic factors and effect on survival of immune-related adverse events in patients with non-small-cell lung cancer treated with immune checkpoint blockage. [2021]

7. Spain pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitor-mediated colitis in a patient with epidermoid metastatic lung cancer: new and emerging toxicities. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

The Balancing Act between Cancer Immunity and Autoimmunity in Response to Immunotherapy. [2020]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitor-associated toxicity in advanced non-small cell lung cancer: An updated understanding of risk factors. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Effect of a multidisciplinary Severe Immunotherapy Complications Service on outcomes for patients receiving immune checkpoint inhibitor therapy for cancer. [2022]

11. United States 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. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Gene immunotherapy for non-small cell lung cancer. [2019]

13. England pubmed.ncbi.nlm.nih.gov

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14. Ireland pubmed.ncbi.nlm.nih.gov

Gemcitabine plus cisplatin vs. gemcitabine plus carboplatin in stage IIIb and IV non-small cell lung cancer: a phase III randomized trial. [2022]