Atezolizumab + Cobimetinib for Lung Cancer

Not currently recruiting at 18 trial locations

Overseen By Raid Aljumaily

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, CYP3A4 inhibitors

Disqualifiers: CNS metastases, Autoimmune disease, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: 28 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two treatments, atezolizumab and cobimetinib, in treating non-small cell lung cancer that has spread, returned, or resisted other treatments. Atezolizumab (Tecentriq) is an immunotherapy that helps the immune system attack cancer, while cobimetinib (Cotellic) blocks a protein that promotes cancer cell growth. Both treatments aim to slow or stop cancer spread. Suitable candidates include those with non-small cell lung cancer resistant to PD-1/PD-L1 therapies, who know their cancer's KRAS mutation status, and who have tried other unsuccessful treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain medications like strong or moderate inhibitors or inducers of CYP3A4 enzymes, and systemic immunosuppressive medications within 2 weeks before starting the trial. It's best to 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 the combination of atezolizumab and cobimetinib is generally well-tolerated by patients with various types of cancer, including non-small cell lung cancer. Studies have found that patients can usually manage the side effects at the tested doses. While some side effects may occur, they are typically not severe. This suggests that the treatment might be safe for most people considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of atezolizumab and cobimetinib for lung cancer because these drugs work together in a unique way. Atezolizumab is an immunotherapy that helps the immune system recognize and attack cancer cells, while cobimetinib is a targeted therapy that inhibits a pathway involved in cancer cell growth. This combination targets both the immune system and specific cancer cell mechanisms, potentially offering a more comprehensive approach than traditional chemotherapy, which primarily targets rapidly dividing cells. This dual action could lead to more effective treatment with potentially fewer side effects than conventional methods.

What evidence suggests that atezolizumab and cobimetinib might be effective for non-small cell lung cancer?

Research has shown that the combination of atezolizumab and cobimetinib, which participants in this trial will receive, may help treat certain cancers, such as non-small cell lung cancer (NSCLC). Studies have found that atezolizumab can extend the lives of patients with advanced NSCLC by boosting the immune system to fight cancer cells. Cobimetinib blocks signals that prompt cancer cells to grow. Together, these drugs aim to slow or stop the spread of cancer. Early results suggest this combination could be a viable option for patients whose cancer has spread or hasn't responded to other treatments. ^{1 4 6 7 8}

Who Is on the Research Team?

Stephen V. Liu

Principal Investigator

JHU Sidney Kimmel Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

Adults with metastatic, recurrent, or treatment-resistant non-small cell lung cancer who have previously not responded well to anti-PD-1/PD-L1 therapy. Participants must be over 18, have measurable disease, and acceptable organ function. Those with certain gene mutations may join specific cohorts. Pregnant women and individuals with uncontrolled diseases or recent significant adverse events from cancer therapies are excluded.

Inclusion Criteria

My lung cancer is confirmed to be metastatic or recurrent through testing.

Your hemoglobin level is at least 8 grams per deciliter.

My cancer progressed or I couldn't tolerate treatment for my EGFR, ALK, or ROS1 mutation.

Exclusion Criteria

You have had allergic reactions to drugs similar to atezolizumab or cobimetinib.

I do not have another cancer that needs treatment within 2 years, except for certain low-risk types.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab intravenously and cobimetinib orally. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

1 visit (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, including CT scan, MRI, biopsy, and blood collection.

90 days

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Cobimetinib

Trial Overview

The trial is testing the combination of atezolizumab (an immunotherapy drug) and cobimetinib (a kinase inhibitor for cancers with a mutated BRAF gene) in patients whose lung cancer has spread or resisted previous treatments. The study aims to see if this drug combo is more effective than current standard care.

How Is the Trial Designed?

Group I: Treatment (atezolizumab, cobimetinib) Experimental Treatment 6 Interventions

Patients receive atezolizumab IV over 30-60 minutes on days 1, and cobimetinib PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity. Patients also undergo a CT scan, MRI, biopsy, and collection of blood throughout the trial.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Atezolizumab, an immune checkpoint inhibitor, has been shown to significantly prolong overall survival in patients with advanced non-small cell lung cancer (NSCLC) who have previously received chemotherapy, based on results from the phase II POPLAR and phase III OAK trials.

The treatment is particularly effective in patients with higher PD-L1 expression, demonstrating higher objective response rates, and it has a manageable safety profile with a low incidence of immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Previously Treated Advanced Non-Small Cell Lung Cancer. Blair, HA.[2020]

Atezolizumab significantly improves overall survival (OS) and progression-free survival (PFS) in patients with advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, based on a meta-analysis of 7 randomized clinical trials involving 4,859 patients.

The effectiveness of atezolizumab varies based on clinical and molecular features, with better outcomes observed in younger patients, those with wild-type EGFR, and active or previous smokers, highlighting the importance of personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Atezolizumab for Advanced Non-Small Cell Lung Cancer Based on Clinical and Molecular Features: A Meta-Analysis. Liu, W., Huo, G., Chen, P.[2022]

Atezolizumab significantly improves overall survival in patients with metastatic non-small cell lung cancer (mNSCLC), with median survival times of 13.8 months in the atezolizumab group compared to 9.6 months in the docetaxel group in the OAK trial.

The treatment has an acceptable safety profile, with common side effects including fatigue and decreased appetite, and serious immune-related adverse events occurring in a small percentage of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. Weinstock, C., Khozin, S., Suzman, 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 is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

Atezolizumab, the first anti-PD-L1 monoclonal antibody approved by the FDA, has shown promising efficacy in treating metastatic triple-negative breast cancer, supported by data from the Phase III IMpassion130 trial.

The review highlights the pharmacodynamic and pharmacokinetic properties of atezolizumab, emphasizing its safety and effectiveness in various cancers, including small-cell lung cancer and renal cell cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. Mavratzas, A., Seitz, J., Smetanay, K., et al.[2020]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

Atezolizumab, an immunotherapy targeting PD-L1, has shown promising efficacy in treating non-small-cell lung cancer (NSCLC), particularly in clinical trials like the phase II FIR and BIRCH studies, which evaluated its effectiveness based on PD-L1 expression.

In randomized trials (POPLAR and OAK), atezolizumab demonstrated improved efficacy compared to standard chemotherapy (docetaxel) in previously treated NSCLC patients, suggesting a favorable risk-benefit ratio for second-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospects and progress of atezolizumab in non-small cell lung cancer. Vansteenkiste, J., Wauters, E., Park, K., et al.[2019]

Atezolizumab, an anti-PD-L1 therapy, has shown promising results in treating advanced non-small-cell lung cancer (NSCLC), particularly in patients who have already undergone other treatments.

Emerging evidence suggests that administering atezolizumab earlier, especially in combination with chemotherapy and bevacizumab, may enhance its effectiveness, highlighting the importance of patient selection based on clinical and immune-related factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of atezolizumab in the treatment of metastatic non-small-cell lung cancer: patient selection and perspectives. Facchinetti, F., Bordi, P., Leonetti, A., et al.[2023]

Atezolizumab, a PD-L1 blocking antibody, shows higher rates of objective response, progression-free survival, and overall survival when used as a first-line therapy in chemotherapy-naïve patients with metastatic non-small cell lung cancer (NSCLC), compared to its use in later treatment lines.

The review included 15 ongoing studies, with 5 reporting results, indicating that atezolizumab is being explored in various treatment combinations and settings, suggesting its potential as a versatile first-line treatment option for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for the First-Line Treatment of Non-small Cell Lung Cancer (NSCLC): Current Status and Future Prospects. Ryu, R., Ward, KE.[2023]

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, cemiplimab, and pembrolizumab are established as standard first-line immunotherapy options for patients with advanced non-small cell lung cancer (NSCLC) who have high PD-L1 expression (≥50%).

The consensus among 25 Spanish lung cancer experts indicates that these therapies can be tailored to specific patient subgroups, enhancing treatment decision-making based on differences observed in pivotal clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 Inhibitors as Monotherapy in the First-Line Treatment of Advanced Non-Small Cell Lung Cancer Patients with High PD-L1 Expression: An Expert Position Statement. Isla, D., Sánchez, A., Casal, J., et al.[2023]

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