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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with non-small cell lung cancer (NSCLC) that has either recurred after treatment or metastasized. The trial aims to determine the safest and most effective dose of two drugs, vismodegib and atezolizumab, which may work better together than separately. Vismodegib may inhibit tumor growth by blocking key enzymes, while atezolizumab, an immunotherapy, helps the immune system combat cancer. The trial seeks participants who have tried standard NSCLC treatments but still need options. 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 combination therapy.

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.

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

Previous studies have shown that atezolizumab helps people with advanced non-small cell lung cancer (NSCLC) live longer, suggesting it is generally well-tolerated. Vismodegib stops tumor growth by blocking certain enzymes. Although its safety in lung cancer is less understood, it has been used for conditions like basal cell carcinoma.

As this is an early phase study, the main goal is to assess safety and determine the best dose when using vismodegib and atezolizumab together. While evidence exists for the safety of each drug individually, their combined use is still under investigation. Early trials like this one are crucial for understanding treatment tolerance and identifying side effects. The combination appears promising, and participation will help gather more information on its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of vismodegib and atezolizumab for lung cancer because it offers a novel approach to treatment. While most existing treatments for lung cancer focus on targeting specific mutations or using chemotherapy, vismodegib works by inhibiting the Hedgehog signaling pathway, which is involved in the growth and spread of cancer cells. Atezolizumab, on the other hand, is an immunotherapy that helps the immune system recognize and attack cancer cells. By combining these two mechanisms, this treatment has the potential to enhance the body's natural defenses against cancer while simultaneously disrupting the pathways cancer cells use to grow, which could lead to more effective outcomes for patients.

What evidence suggests that the combination of vismodegib and atezolizumab could be effective for non-small cell lung cancer?

Research has shown that atezolizumab, a type of immunotherapy, can help people with non-small cell lung cancer (NSCLC) live longer by enhancing the immune system's ability to fight cancer. Studies have found that atezolizumab is particularly beneficial for patients whose cancer cells express high levels of the molecule PD-L1. Vismodegib, in contrast, inhibits cancer cell growth by blocking essential enzymes. In this trial, participants will receive a combination of vismodegib and atezolizumab, as researchers are investigating whether these drugs might be more effective together, potentially offering greater benefits than when used separately. This combination could be promising for those with NSCLC that has recurred or spread. ^{1 3 6 7 8}

Who Is on the Research Team?

Dwight Owen, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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, 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 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 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, 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, 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, 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06616623

NCT06616623 | Vismodegib and Atezolizumab for the ... Vismodegib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as ...

2. withpower.com withpower.com/trial/vismodegib-atezolizumab-for-lung-cancer-0d903

Vismodegib + Atezolizumab for Lung Cancer What data supports the effectiveness of the drug Atezolizumab for lung cancer? Atezolizumab has been shown to significantly improve overall survival in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10477621/

Immune checkpoint inhibitors in non-small cell lung cancer Following this study, in October 2021, the FDA approved the use of atezolizumab for use in the maintenance treatment of stage II–III NSCLC with PD-L1 expressed ...

4. clinicaltrialsarena.com clinicaltrialsarena.com/news/newscancer-research-uk-reports-positive-phase-iii-oak-trial-of-atezolizumab-in-treating-lunch-cancer-5696114/

Cancer Research UK reports positive Phase III OAK trial of ... According to study findings, atezolizumab was more effective for patients with the highest levels of the PD-L1 molecule on their cells. "This is ...

5. roche.com roche.com/media/releases/med-cor-2018-09-06

Roche to present new data from its extensive lung cancer ... New and updated pivotal data from the TECENTRIQ lung programme, including overall survival (OS) and progression-free survival (PFS) results ...

6. roche.com roche.com/media/releases/med-cor-2020-05-07

New data at the ASCO20 Virtual Scientific Program reflects ... ... outcomes data for patients with metastatic lung cancer, #TPS2087 ... outcomes with atezolizumab (atezo) + platinum-based chemotherapy ...

7. app.trialscreen.org app.trialscreen.org/trials/phase-1-vismodegib-atezolizumab-treatment-recurrent-or-metastatic-non-small-trial-nct06616623

Vismodegib and Atezolizumab for the Treatment of ... The study may also provide valuable information about the safety and effectiveness of this combination therapy, which could benefit future patients. Risks: As ...

8. cancer.osu.edu cancer.osu.edu/for-patients-and-caregivers/learn-about-cancers-and-treatments/innovation-at-the-james/clinical-trials/find-a-clinical-trial/a-phase-ib-study-of-vismodegib-and-atezolizumab

A Phase Ib Study of Vismodegib and Atezolizumab in Patients ... A Phase Ib Study of Vismodegib and Atezolizumab in Patients with Advanced Non-Small Cell Lung Cancer (ML43922) ; Study Status Open To Accrual ; National Clinical ...