What side effects are associated with this type of intervention?

Common side effects of lung cancer immunotherapies, including those similar to the COH06 trial with genetically modified NK cells, often involve immune-related adverse events such as pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Cytokine-induced therapies can also cause flu-like symptoms, fatigue, and injection site reactions. Severe immune-mediated reactions, though less frequent, may require corticosteroid treatment.

What prior FDA approvals exist?

Several immunotherapy drugs have received FDA approval for the treatment of non-small cell lung cancer (NSCLC). Atezolizumab, a PD-L1 inhibitor, is approved for use in various settings, including in combination with chemotherapy. Nivolumab, a PD-1 inhibitor, is another approved option for NSCLC, often used in the second-line setting after chemotherapy. Durvalumab, also a PD-L1 inhibitor, is approved for patients with unresectable stage III NSCLC whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. These treatments are similar to the investigational COH06 trial, which explores genetically modified NK cells expressing PD-L1 and secreting IL-15, aiming to enhance the immune system's ability to attack cancer cells.

What other types of research exist?

Promising novel alternatives to COH06 for lung cancer patients include: 1) Combination of cytokine-induced killer (CIK) cells with PD-1 inhibitors (e.g., nivolumab) and ALK inhibitors (e.g., crizotinib), which have shown substantial variability but potential efficacy in NSCLC cell lines. 2) Anti-PD-1 monoclonal antibodies (e.g., pembrolizumab, nivolumab) combined with other therapies like VEGF pathway blockers or CTLA-4 inhibitors. 3) Therapeutic vaccines such as Sipuleucel-T, which are being explored for their ability to enhance immune response against tumors. These alternatives offer different mechanisms of action and may provide effective treatment options for lung cancer patients.

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CAR T-cell Therapy

NK Cells +/− Atezolizumab for Lung Cancer

Phase 1

Waitlist Available

Led By Miguel A Villalona-Calero

Research Sponsored by City of Hope Medical Center

Eligibility Criteria Checklist

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

Must have

Lung non-small cell carcinoma (NSCLC) patients with advanced, metastatic, or recurrent disease, previously treated with a PD-1 or PD-L1 immune checkpoint inhibitor, either as single agent or in combination with chemotherapy or other immunotherapy or experimental agents

Eastern Cooperative Oncology Group (ECOG) 0 or 1

Must not have

Severe (grade 3 or higher) immune related adverse events during prior PD-1 inhibitor treatment

Active diarrhea

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new treatment using modified immune cells from umbilical cord blood to fight advanced lung cancer that didn't respond to previous treatments. Some patients will also receive a drug that boosts the immune system's ability to attack cancer. The goal is to find the best dose and see if the treatment is safe and effective.

Who is the study for?

Adults with advanced non-small cell lung cancer that has worsened after treatment with PD-1/PD-L1 inhibitors. They must not have HIV, active hepatitis B or C, and should have normal organ function. Pregnant or breastfeeding women can't join, nor can those with certain mutations in their tumors unless specific treatments failed.

What is being tested?

The trial is testing COH06 (genetically modified NK cells) alone or combined with Atezolizumab to see if they help fight lung cancer better. It's a phase I study to determine the right dose and observe side effects when treating patients whose cancer didn't respond to previous therapies.

What are the potential side effects?

Possible side effects include immune reactions due to NK cells or Atezolizumab, such as inflammation in various organs, infusion-related reactions, fatigue, blood disorders like anemia and low platelet counts, increased risk of infections and potential allergic responses.

Eligibility Criteria

Inclusion Criteria

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

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I have advanced NSCLC and was treated with PD-1 or PD-L1 inhibitors.

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

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I am 18 years old or older.

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I have recovered from side effects of cancer treatment, except for hair loss.

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My cancer has grown despite treatment with a PD-1/PD-L1 inhibitor.

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I haven't had chemotherapy or immunotherapy in the last 3 weeks.

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My body has recovered from previous medication side effects, except for hair loss or mild anemia.

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My lung cancer is confirmed to be non-small cell type.

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My kidneys are working well, as shown by a test.

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My blood clotting time is near normal and I'm not on blood thinners.

Exclusion Criteria

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

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I experienced severe side effects from previous PD-1 inhibitor treatment.

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I am currently experiencing diarrhea.

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I am not pregnant or breastfeeding.

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I haven't had chemotherapy, radiation, or immunotherapy in the last 21 days.

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I have a serious illness that is not under control.

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I am currently taking antibiotics for an infection.

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I have been diagnosed with Gilbert's disease.

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I had a stem cell transplant using my own cells within the last year.

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I do not have any other active cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Incidence of adverse events - ASTCT

Incidence of adverse events - CTCAE

Secondary study objectives

Disease Control Rate (DCR)

Overall Response Rate (ORR)

Overall Survival (OS)

+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: Treatment (fludarabine, cyclophosphamide, COH06, atezolizumab)Experimental Treatment5 Interventions

Patients receive fludarabine IV on days -5 to -3, cyclophosphamide IV on days -5 to -3, and COH06 IV on days 0, 7, 14, and 21 in the absence of disease progression or unacceptable toxicity. Patients assigned to dose level 4 also receive atezolizumab IV over 60 minutes on days 0, 14, 28, and 42 in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Atezolizumab

2016

Completed Phase 3

~5860

Biospecimen Collection

2004

Completed Phase 3

~2020

Cyclophosphamide

2010

Completed Phase 4

~2310

Fludarabine

2012

Completed Phase 4

~1860

0 / 19Eligibility 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 lung cancer, particularly advanced non-small cell lung cancer (NSCLC), include immunotherapies that harness the body's immune system to target and destroy cancer cells. Treatments like the COH06 trial use genetically modified natural killer (NK) cells that express PD-L1 and secrete IL-15. These modifications enhance the NK cells' ability to kill tumor cells and prolong their survival. Additionally, monoclonal antibodies such as atezolizumab target immune checkpoint pathways, helping the immune system recognize and attack cancer cells. These therapies are significant for lung cancer patients as they offer a targeted approach that can improve overall survival and progression-free survival, especially in cases where traditional treatments have failed.

Comparative beneficiary effects of immunotherapy against chemotherapy in patients with advanced NSCLC: Meta-analysis and systematic review.