Vismodegib + Atezolizumab for Lung Cancer

Overseen By The Ohio State Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dwight Owen

Must not be taking: Systemic steroids, Immunosuppressants

Disqualifiers: Autoimmune disease, CNS metastases, Cardiovascular disease, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: Up to 2 years

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase Ib trial tests the safety, side effects, and best dose of the combination of vismodegib and atezolizumab in treating patients with non-small cell lung cancer (NSCLC) that has come back after a period of improvement (recurrent) or has spread from where it first started (primary site) to other places in the body (metastatic). Vismodegib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving a combination of vismodegib and atezolizumab may be safe, tolerable and/or effective than either drug alone in treating patients with recurrent or metastatic NSCLC.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy at doses greater than 10 mg prednisone or equivalent, or other immunosuppressive therapy, you may need to stop these 14 days before starting the trial treatment.

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

Atezolizumab has been shown to significantly improve overall survival in patients with advanced non-small cell lung cancer who have previously received chemotherapy, as demonstrated in the phase II POPLAR and phase III OAK trials. It also has a favorable safety profile with manageable side effects. ^{1 2 3 4 5}

Is the combination of Vismodegib and Atezolizumab safe for humans?

Atezolizumab, also known as Tecentriq, has been shown to have an acceptable safety profile in clinical trials for lung and bladder cancer. Common side effects include fatigue, decreased appetite, and nausea, while more serious effects can include pneumonia and liver inflammation. Vismodegib, known as Erivedge, is generally used for skin cancer, and its safety profile includes muscle spasms and hair loss. ^{1 3 4 6 7}

What makes the drug combination of Vismodegib and Atezolizumab unique for lung cancer treatment?

The combination of Vismodegib and Atezolizumab is unique because it pairs a drug that targets the Hedgehog signaling pathway (Vismodegib) with a PD-L1-blocking antibody (Atezolizumab), potentially enhancing the immune system's ability to fight lung cancer by reducing tumor growth signals and boosting immune response. ^{1 3 4 6 8}

Research Team

Dwight Owen, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with non-small cell lung cancer that has either returned after getting better or spread to other parts of the body. Participants must have measurable disease and be able to undergo procedures like blood draws and scans.

Inclusion Criteria

Willing to comply with study procedures

Albumin ≥ 2.5 g/dL

My blood clotting time is normal or near normal, unless I'm on blood thinners.

Exclusion Criteria

I have had a transplant of stem cells or an organ from another person.

I have not had a severe infection in the last 4 weeks.

I have no health issues that prevent me from taking the study drug.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive vismodegib orally daily and atezolizumab intravenously on day 1 of each 28-day cycle

Up to 2 years

Monthly visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 12 weeks

Quarterly visits (in-person)

Treatment Details

Interventions

• Atezolizumab
• Vismodegib

Trial Overview The trial is testing a combination of two drugs, Vismodegib and Atezolizumab, to see if they're safe together, what the best dose might be, and how well they work against recurrent or metastatic NSCLC.

Participant Groups

Group I: Treatment (vismodegib, atezolizumab) Experimental Treatment 5 Interventions

Patients receive vismodegib PO daily on days 1-28 and atezolizumab IV on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and blood sample collection throughout the study. Some patients undergo tissue sample collection during screening and on study.

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?

Dwight Owen

Lead Sponsor

Trials

6

Recruited

210+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

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, 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 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 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, 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 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, 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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. [2019]

2. France pubmed.ncbi.nlm.nih.gov

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

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

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. [2020]

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

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

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

8. New Zealand pubmed.ncbi.nlm.nih.gov

Profile of atezolizumab in the treatment of metastatic non-small-cell lung cancer: patient selection and perspectives. [2023]