NK Cells +/− Atezolizumab for Lung Cancer

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, Irvine

Must not be taking: Anticoagulants, Investigational agents

Disqualifiers: Active infection, Other malignancy, Brain metastases, others

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

Compensation: Varies

Number of Visits: 7

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for non-small cell lung cancer that has spread and hasn't responded to previous treatments. The study examines the safety and effectiveness of using special immune cells from umbilical cord blood, called NK cells, either alone or with the drug atezolizumab (Tecentriq). These treatments may enhance the immune system's ability to fight cancer. Individuals with non-small cell lung cancer that hasn't improved with other immune treatments and shows signs of spreading might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you have not received chemotherapy, radiation therapy, biological therapy, or immunotherapy within 21 days before starting the study treatment. It does not specify other medications, so you should discuss your current medications with the study team.

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

Research has shown that NK cell therapies, such as COH06, are generally safe and well-tolerated. Most side effects are mild and resolve on their own, though some serious side effects can occur, albeit less frequently.

Atezolizumab, another component of the trial, demonstrated safety in past studies. Patients typically tolerate this drug well without major issues. Its approval for certain types of cancer provides some confidence in its safety.

As this trial is in an early stage, the primary goal is to determine the safest dose. Researchers are closely monitoring for any side effects. While both treatments have shown promise in previous studies, the trial remains essential to ensure maximum safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this combination treatment for lung cancer because it targets the disease in a novel way. Unlike standard chemotherapy, which attacks rapidly dividing cells, this treatment uses COH06, a type of natural killer (NK) cell therapy, to specifically target and destroy cancer cells. Additionally, it incorporates atezolizumab, an immunotherapy that helps the immune system recognize and fight cancer more effectively. This dual approach not only aims to enhance the immune response but also potentially reduces the risk of cancer progression, offering a new hope for patients with lung cancer.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that atezolizumab is effective for individuals with advanced non-small cell lung cancer (NSCLC) who have previously undergone treatment. Studies found that patients taking atezolizumab lived longer than those receiving chemotherapy, with a 41% lower risk of death for those on atezolizumab. In this trial, participants will receive COH06, a new treatment using specially modified NK cells to target cancer. These NK cells are designed to survive longer and destroy more cancer cells. Some participants will also receive atezolizumab alongside COH06, which could offer a promising option for treating advanced lung cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

Miguel Villalona, MD

Principal Investigator

University of California, Irvine

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

Your liver enzyme levels are not too high.

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

Your disease can be measured using specific criteria called RECIST 1.1.

Exclusion Criteria

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

Concomitant use of other investigational agents

My cancer has EGFR mutations or ALK translocations and treatments have not worked.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Patients receive fludarabine and cyclophosphamide intravenously to prepare for COH06 infusion

1 week

3 visits (in-person)

Treatment

Patients receive COH06 infusions on days 0, 7, 14, and 21. Patients at dose level 4 also receive atezolizumab on days 0, 14, 28, and 42

6 weeks

4-6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

30 days, then every 8 weeks until disease progression, and annually for 15 years

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• COH06

Trial Overview

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.

How Is the Trial Designed?

Group I: Treatment (fludarabine, cyclophosphamide, COH06, atezolizumab) Experimental Treatment 5 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.

Who Is Running the Clinical Trial?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

CytoImmune Therapeutics

Collaborator

Trials

1

Recruited

6+

Published Research Related to This Trial

Atezolizumab therapy significantly improves overall survival (median OS of 11.2 months) in patients with previously treated advanced non-small cell lung cancer (NSCLC), demonstrating its efficacy in a diverse patient population.

The treatment has a manageable safety profile, with serious adverse events occurring in only 8.0% of patients and no new safety signals identified, indicating it is a viable option for patients often excluded from clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final results from TAIL: updated long-term efficacy of atezolizumab in a diverse population of patients with previously treated advanced non-small cell lung cancer. Ardizzoni, A., Azevedo, S., Rubio-Viqueira, B., et al.[2022]

In a phase 2 trial involving 287 patients with previously treated advanced non-small-cell lung cancer (NSCLC), atezolizumab significantly improved overall survival (12.6 months) compared to docetaxel (9.7 months), with a hazard ratio of 0.73, indicating a 27% reduction in the risk of death.

The efficacy of atezolizumab was found to correlate with PD-L1 expression levels on tumor cells and immune cells, suggesting that higher PD-L1 expression may predict better outcomes with this treatment, while atezolizumab also demonstrated a better safety profile with fewer severe adverse events compared to docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Fehrenbacher, L., Spira, A., Ballinger, M., et al.[2022]

Atezolizumab, a monoclonal antibody targeting PD-L1, has shown significant improvements in progression-free and overall survival in patients with advanced non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) when combined with chemotherapy, as demonstrated in the IMpower studies.

The safety profile of atezolizumab in combination with chemotherapy is acceptable, with common immune-related adverse events including rash (18-28%), hypothyroidism (8-15%), and hepatitis (5-17%), consistent with its known effects as a single agent, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. Manzo, A., Carillio, G., Montanino, A., et al.[2022]

A network meta-analysis of five trials showed that PD-1 inhibitors (pembrolizumab and nivolumab) had higher overall response rates (ORR) compared to the PD-L1 inhibitor (atezolizumab), particularly in patients with high PD-L1 expression.

Both pembrolizumab and nivolumab demonstrated superior overall survival (OS) benefits in various patient subgroups, but treatment decisions should also consider individual patient characteristics and safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of immunotherapies targeting the PD-1/PD-L1 pathway for previously treated advanced non-small cell lung cancer: A Bayesian network meta-analysis. Almutairi, AR., Alkhatib, N., Martin, J., et al.[2019]

Atezolizumab monotherapy demonstrated a manageable safety profile in Chinese patients with previously treated advanced non-small cell lung cancer (NSCLC), with serious adverse events occurring in 25.7% of patients and immune-related adverse events in 47.5%.

The treatment showed clinically meaningful efficacy, with a median overall survival of 15.31 months and a 24-month overall survival rate of 37.4%, while specific gene mutations and the presence of CD8+ TILs were associated with better responses to the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of atezolizumab in Chinese patients with previously treated locally advanced or metastatic non-small cell lung cancer: An open-label, single-arm, multicenter study. Xu, Y., Huang, Z., Chang, J., et al.[2023]

In a phase 1 study involving 17 patients with relapsed or refractory small-cell lung cancer (SCLC), atezolizumab was generally well tolerated, with 64.7% experiencing any-grade treatment-related adverse events, the most common being fatigue.

Atezolizumab showed some antitumor activity, with a partial response in 5.9% of patients and a median overall survival of 5.9 months, suggesting potential benefits for patients with high T-effector gene signature and PD-L1 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer. Chiang, AC., Sequist, LVD., Gilbert, J., et al.[2021]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

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