NK Cells +/− Atezolizumab for Lung Cancer

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

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

6 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

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 atezolizumab safe for humans?

Atezolizumab has been shown to be generally safe in humans, with serious treatment-related side effects occurring in a small percentage of patients. Studies in diverse populations with lung cancer found no new safety concerns, indicating it is well-tolerated. ^{1 2 3 4 5}

How is the treatment with NK Cells and Atezolizumab unique for lung cancer?

This treatment combines NK cells (natural killer cells, which are part of the immune system that can attack cancer cells) with Atezolizumab, a drug that helps the immune system recognize and fight cancer by blocking a protein called PD-L1. This combination aims to enhance the body's immune response against lung cancer, offering a novel approach compared to traditional chemotherapy. ^{1 4 6 7 8}

What data supports the effectiveness of the drug Atezolizumab for lung cancer?

Research shows that Atezolizumab, a drug that helps the immune system fight cancer, is effective in treating non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) by blocking a protein that allows cancer cells to hide from the immune system. ^{2 4 6 9 10}

Who Is on the Research Team?

Stephen Forman, MD

Principal Investigator

City of Hope Medical Center

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?

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 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]

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]

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]

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]

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]

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 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]

Citations

1. England 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. [2022]

2. Ireland 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. [2023]

3. England pubmed.ncbi.nlm.nih.gov

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. [2022]

4. United States 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. [2021]

5. Netherlands 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. [2019]

6. England 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. [2022]

7. England 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. [2022]

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

Atezolizumab in Japanese Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer: A Subgroup Analysis of the Phase 3 OAK Study. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Atezolizumab for the treatment of non-small cell lung cancer. [2019]

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

Safety and clinical activity of atezolizumab monotherapy in metastatic non-small-cell lung cancer: final results from a phase I study. [2021]