What is the mechanism of action of this treatment?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) include immune checkpoint inhibitors like Atezolizumab and gene therapy approaches such as ADV/IL-12. Atezolizumab, a PD-L1 inhibitor, blocks the interaction between PD-L1 on tumor cells and PD-1 on T-cells, preventing the tumor from evading the immune system and allowing T-cells to attack the cancer. ADV/IL-12 gene therapy delivers the gene for interleukin-12 (IL-12) to stimulate an immune response, enhancing the activity of natural killer cells and T-cells against the tumor. These treatments are significant for NSCLC patients as they leverage the body's immune system to combat cancer, potentially improving outcomes and extending survival.

What side effects are associated with this type of intervention?

Atezolizumab, a PD-L1 inhibitor, is associated with treatment-related grade 3/4 adverse events in 27% to 68% of patients, including fatigue, rash, diarrhea, and pneumonitis. Immune checkpoint inhibitors like Atezolizumab can also cause immune-related adverse events such as colitis, hepatitis, endocrinopathies, and pneumonitis. ADV/IL-12 gene therapy, which aims to stimulate the immune system, may have side effects including flu-like symptoms, injection site reactions, and potential immune-related adverse events. Overall, these treatments can lead to significant but manageable side effects, which should be discussed with a healthcare provider.

What prior FDA approvals exist?

Atezolizumab, a PD-L1 inhibitor, is FDA approved for the front-line treatment of NSCLC with high PD-L1 expression (≥50% of tumor cells or ≥10% of tumor-infiltrating immune cells) without EGFR or ALK genomic alterations. Pembrolizumab, another PD-1 inhibitor, is approved for similar indications and has shown efficacy in combination with chemotherapy for both squamous and non-squamous NSCLC. Cemiplimab, a PD-1 inhibitor, is also approved for advanced NSCLC with PD-L1 expression ≥50%. These approvals are based on improved overall survival and progression-free survival in clinical trials. Immune-stimulating therapies like ADV/IL-12 gene therapy are still under investigation and not yet FDA approved.

What other types of research exist?

Promising alternatives for NSCLC treatment in 2024 include Pembrolizumab, which has shown efficacy in various trials, particularly for patients with high PD-L1 expression. Nivolumab is another PD-1 inhibitor with demonstrated intracranial response in patients with brain metastases. Additionally, Lorlatinib has shown significant brain penetration and efficacy in ALK-positive NSCLC. Alectinib is effective against systemic disease and brain metastases in ALK-rearranged NSCLC. Osimertinib is beneficial for patients with EGFR mutations, including those with leptomeningeal metastases. These treatments offer various mechanisms of action and target different genetic profiles, providing a range of options for personalized therapy.

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Monoclonal Antibodies

Atezolizumab + IL-12 Gene Therapy for Non-Small Cell Lung Cancer

Phase 1

Waitlist Available

Research Sponsored by Eric Bernicker, MD

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Cardiac ejection fraction of ≥45%

Willing to provide biopsy tissue as required by the study

Must not have

Prior allogeneic stem cell or solid organ transplantation

Uncontrolled or symptomatic hypercalcemia

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 12 weeks

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of a drug called atezolizumab and a gene therapy that delivers a specific protein directly into tumors. The goal is to see if this combination can safely enhance the immune system's ability to fight advanced lung cancer that hasn't responded to standard treatments.

Who is the study for?

This trial is for adults with metastatic non-small cell lung cancer that worsened after first-line immunotherapy, with or without chemo. They must have a life expectancy of at least 6 months, measurable disease, and be able to provide biopsy tissue. Participants need to agree to use contraception and not have severe allergies, active infections, heart issues within the last 3 months, or other conditions that could interfere with the study.

What is being tested?

The trial tests Atezolizumab combined with ADV/IL-12 gene therapy in patients whose lung cancer has progressed despite treatment. It's a Phase I study focused on safety and requires participants' tumors to be accessible for gene therapy administration.

What are the potential side effects?

Potential side effects may include allergic reactions related to antibodies or fusion proteins used in treatments, immune system complications due to gene therapy, as well as general risks associated with immunotherapies such as fatigue and inflammation.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My heart pumps blood effectively.

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I am willing to provide tissue samples for the study.

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My lung cancer has spread and was confirmed by a lab test.

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I am 18 years old or older.

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I am fully active or restricted in physically strenuous activity but can do light work.

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My tumor can be reached for treatment injections.

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My cancer has worsened despite initial immunotherapy.

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I agree to either not have sex or use a condom.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had a previous transplant of stem cells or an organ.

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I have high calcium levels in my blood that are causing symptoms.

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I frequently need procedures to remove excess fluid from my chest or abdomen.

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I have a history of specific lung conditions without a known cause.

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I have active tuberculosis.

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I have had cancer spread to the lining of my brain and spinal cord.

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My cancer pain is not managed with current treatment.

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I have cancer that has spread to my brain or surrounding membranes.

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I am currently on medication for hepatitis B.

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I have previously received gene therapy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 12 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~12 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 12 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression-free survival plus stable disease after 6 cycles

Secondary study objectives

Health-Related Quality-of-Life (HRQOL)

Overall Survival

Patient-reported outcomes (PRO)

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Atezolizumab and Interleukin-12 Gene TherapyExperimental Treatment1 Intervention

0 / 18Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Non-Small Cell Lung Cancer (NSCLC) include immune checkpoint inhibitors like Atezolizumab and gene therapy approaches such as ADV/IL-12. Atezolizumab, a PD-L1 inhibitor, blocks the interaction between PD-L1 on tumor cells and PD-1 on T-cells, preventing the tumor from evading the immune system and allowing T-cells to attack the cancer. ADV/IL-12 gene therapy delivers the gene for interleukin-12 (IL-12) to stimulate an immune response, enhancing the activity of natural killer cells and T-cells against the tumor. These treatments are significant for NSCLC patients as they leverage the body's immune system to combat cancer, potentially improving outcomes and extending survival.