Vismodegib + Atezolizumab for Lung Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Dwight Owen, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Dwight Owen

Must not be taking: Systemic steroids, Immunosuppressants

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

No Placebo Group

Breakthrough Therapy

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}

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.

Trial 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 (Monoclonal Antibodies)
• Vismodegib (Hedgehog Pathway Inhibitor)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Ohio State University Comprehensive Cancer Center Columbus, OH

Who Is Running the Clinical Trial?

Dwight Owen Lead Sponsor

Genentech, Inc. Industry Sponsor

References

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

Atezolizumab: First Global Approval. [2019] Atezolizumab (Tecentriq™)-a monoclonal antibody targeting programmed death ligand 1 (PD-L1 or CD274 antigen)-is being developed by Genentech as treatment for a variety of haematological malignancies and solid tumours. It been approved in the US as a second-line therapy for urothelial carcinoma and is awaiting approval as a second-line therapy for non-small cell lung cancer. This article summarizes the milestones in the development of atezolizumab leading to this first approval for urothelial carcinoma.

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

Atezolizumab: A Review in Previously Treated Advanced Non-Small Cell Lung Cancer. [2020] Atezolizumab (TECENTRIQ™), an immune checkpoint inhibitor, is an immunoglobulin G1 monoclonal antibody that binds to programmed death ligand 1 (PD-L1) and blocks its interactions with programmed death 1 and B7.1 receptors. Atezolizumab is approved as monotherapy in several countries worldwide for the treatment of patients with advanced non-small cell lung cancer (NSCLC) who have previously received chemotherapy. Approval was based on its clinical benefit in this setting in the phase II POPLAR and phase III OAK trials. In these studies, atezolizumab significantly prolonged overall survival (OS) relative to docetaxel, regardless of PD-L1 status. Increasing PD-L1 expression was associated with OS improvements. Atezolizumab also demonstrated efficacy in the phase II FIR and BIRCH trials, as assessed by objective response rates (ORRs) in patients with tumours expressing PD-L1. Higher ORRs were seen in patients with high PD-L1 expression. Atezolizumab had an acceptable, manageable tolerability profile, with a low incidence of immune-related adverse events. Therefore, atezolizumab is a valuable treatment option for patients with advanced NSCLC that has progressed during or after chemotherapy.

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

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022] Atezolizumab (Tecentriq, MPDL3280A; Genentech/Roche) is an FcγR binding-deficient, fully humanized IgG1 mAb designed to interfere with the binding of PD-L1 ligand to its two receptors, PD-1 and B7.1. By blocking the PD-L1/PD-1 immune checkpoint, atezolizumab reduces immunosuppressive signals found within the tumor microenvironment and, consequently, increases T-cell-mediated immunity against the tumor. Atezolizumab has been FDA approved as second-line therapy for advanced bladder cancer. This accelerated approval was based on phase II trial data in patients with metastatic bladder cancer that showed unexpected and durable tumor responses. In subjects whose tumors progressed on first-line platinum-based chemotherapy, the objective response rate was 15%, the complete response rate was 5%, and 1-year overall survival was 36%. In subjects that were chemotherapy naïve and cisplatin ineligible, the objective response rate was 24%, the complete response rate was 7%, and 1-year overall survival was 57%. Better responses were associated with higher PD-L1 expression on the tumor-infiltrating leukocytes. These data suggest that patients with advanced bladder cancer treated with atezolizumab have significantly better response rates and survival than historical controls treated with other second-line regimens. The toxicity profile of atezolizumab is also favorable. Trials are currently assessing whether atezolizumab is effective in earlier bladder cancer stages and in the first-line metastatic setting. Clin Cancer Res; 23(8); 1886-90. ©2016 AACR.

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] Atezolizumab is a humanised antiprogrammed death-ligand 1 (PD-L1) monoclonal antibody that inhibits PD-L1 and programmed death-1 (PD-1) and PD-L1 and B7-1 interactions, reinvigorating anticancer immunity. We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer.

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

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. [2020] Since the US FDA-approval of the first immune checkpoint inhibitor, anticytotoxic T-lymphocyte antigen-4 monoclonal antibody ipilimumab, for metastatic melanoma on 28 March 2011, another six agents have been granted use among a multitude of tumors, including renal cell cancer, Hodgkin lymphoma, urothelial carcinoma and non-small-cell lung cancer. The first anti-programmed cell death ligand-1 monoclonal antibody to receive the FDA approval, atezolizumab (Tecentriq®), has yielded promising results among international Phase III trials in triple-negative breast cancer and small-cell lung cancer, expanding the field of cancer immunotherapies. Herein, we review the pharmacodynamic and pharmacokinetic properties of atezolizumab, its safety and efficacy data from early clinical trials and summarize data from Phase III IMpassion130 trial, prompting FDA and EMA approval of atezolizumab in metastatic triple-negative breast cancer. Finally, implications for clinical use and ongoing research will be briefly discussed.

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] On October 18, 2016, the FDA approved atezolizumab (TECENTRIQ; Genentech, Inc.) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose disease progressed during or following platinum-containing chemotherapy. Approval was based on demonstration of clinically meaningful improvements in overall survival (OS) and an acceptable safety profile in two randomized clinical trials (OAK and POPLAR). Median OS in OAK, a phase III trial, was 13.8 months [95% confidence interval (CI), 11.8-15.7] in the atezolizumab arm compared with 9.6 months (95% CI, 8.6-11.2) in the docetaxel arm [hazard ratio (HR) = 0.74; 95% CI, 0.63-0.87; P = 0.0004]. Median OS in POPLAR, a phase II trial, was 12.6 months (95% CI, 9.7-16.0) and 9.7 months (95% CI, 8.6-12.0; HR = 0.69; 95% CI, 0.52-0.92) for the atezolizumab and docetaxel arms, respectively. In patients treated with atezolizumab, the most common (≥20%) adverse reactions were fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation; the most common (≥2%) grade 3 to 4 adverse events were dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, musculoskeletal pain, aspartate aminotransferase increase, alanine aminotransferase increase, dysphagia, and arthralgia. Clinically significant immune-related adverse events for patients receiving atezolizumab included 1.4% incidence each of grade 3 to 4 pneumonitis, hepatitis, colitis, and thyroid disease. Clin Cancer Res; 23(16); 4534-9. ©2017 AACR.

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

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. [2022] Atezolizumab is a humanized monoclonal antibody against PD-L1 capable of enhancing antitumor immune activity, with a demonstrated activity as single agent in patients with advanced non-small-cell lung cancer (NSCLC).

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] Programed cell death-1/programed death ligand-1 (PD-1/PD-L1) blockade represents an affirmed reality in the treatment of advanced non-small-cell lung cancer (NSCLC) patients. Atezolizumab, an anti-PD-L1 agent, figures among the drugs that provide previously unenvisaged outcomes in the pretreated setting of metastatic NSCLC. Increasing evidence vouches for the early administration of PD-1/PD-L1 blockers in untreated patients, encompassing atezolizumab combinations with chemotherapy and the anti-angiogenic agent bevacizumab. Moreover, the development of atezolizumab allowed to derive several hints regarding clinical and immunological factors predictive of its activity and efficacy, some of them exclusive among this class of drugs. This review provides an overview of atezolizumab development throughout clinical trials toward its applicability in the routine practice, with a particular focus on patient selection based on clinical and immune-related factors.