Vismodegib and Atezolizumab for the Treatment of Recurrent or Metastatic Non-Small Cell Lung Cancer

NCT06616623 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-23268NCI-2024-07859
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Recurrent Lung Non-Small Cell Carcinoma; Stage IV Lung Cancer AJCC v8; Metastatic Lung Non-Small Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (AEs)

  Will be the measured using the Common Terminology Criteria for Adverse Events version 5 criteria. Frequency and severity of AEs and tolerability of the regimen will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

  Up to 2 years

• Incidence of dose limiting toxicity

  Will be the measured using the Common Terminology Criteria for Adverse Events version 5 criteria. Frequency and severity of AEs and tolerability of the regimen will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

  Up to cycle 1 (1 cycle = 28 days)

Secondary Outcomes (4)

• Objective response rate

  Up to 2 years

• Disease control rate

  Up to 2 years

• Overall survival (OS)

  From initiation of therapy to death, or censored at last follow-up date if the subject is alive, assessed up to 2 years

• Progression free survival (PFS)

  From initiation of therapy to the time of Response Evaluation Criteria in Solid Tumors progression or death, assessed up to 2 years

Study Arms (1)

Treatment (vismodegib, atezolizumab)

EXPERIMENTAL

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.

Biological: Atezolizumab; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Vismodegib

Interventions

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (vismodegib, atezolizumab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (vismodegib, atezolizumab)

Vismodegib DRUG

Given PO

Also known as: Erivedge, GDC 0449, GDC-0449, GDC0449, Hedgehog Antagonist GDC-0449

Treatment (vismodegib, atezolizumab)

Atezolizumab BIOLOGICAL

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG 7446, RG-7446, RG7446, RO 5541267, RO-5541267, RO5541267, Tecentriq

Treatment (vismodegib, atezolizumab)

Biospecimen Collection PROCEDURE

Undergo tissue and blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (vismodegib, atezolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Confirmed recurrent or metastatic non-small cell carcinoma of the lung of any histology without curative options
• Measurable disease based on RECIST v1.1
• Patients must have received standard of care chemotherapy and/or immunotherapy. No limits to prior lines of therapy. Prior PD-1 and/or PD-L1 directed therapies are permitted
• Patients with adenocarcinoma and known actionable mutations with Food and Drug Administration (FDA) approved treatment options must have received all approved and standard of care treatment options (i.e. osimertinib for epidermal growth factor receptor (EGFR), alectinib for anaplastic lymphoma kinase (ALK), etc.). Mutational testing is not required for patients with squamous cell non-small cell lung carcinoma
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Absolute neutrophil count (ANC) ≥ 1,500 /mcL without granulocyte colony-stimulating factor support
• Platelet count ≥ 100,000 /uL without transfusion
• Hemoglobin ≥ 90 g/L (9 g/dL) patients may be transfused to meet this criterion
• Measured or calculated creatinine clearance (calculated using the Cockcroft-Gault formula) ≥ 60 mL/min for subject with creatinine levels ≤ 1.5 x institutional upper limit of normal (ULN)
• Serum total bilirubin ≤ 1.5 x ULN with the following exception:
• Patients with known Gilbert disease: serum bilirubin ≤ 3 x ULN
• Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 x ULN with the following exceptions:
• Patients with documented liver metastases: AST and ALT ≤ 5 x ULN

You may not qualify if:

• Active autoimmune disease requiring treatment or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis, with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are stable on thyroid-replacement hormone are eligible for the study
• Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover ≤ 10% of body surface area
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids
• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at doses \> 10 mg prednisone or equivalent or other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment
• Cirrhosis (Child-Pugh B or worse) or cirrhosis with history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis
• Has symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with asymptomatic CNS lesions will be eligible if considered appropriate by the treating physician. Subjects with previously treated brain metastases may participate provided they have had a stable neurological status for at least 2 weeks after completion of definitive therapy
• Asymptomatic patients with treated CNS lesions are eligible, provided that all of the following criteria are met:
• Measurable disease, per RECIST v1.1, must be present outside the CNS
• The patient has no history of intracranial hemorrhage or spinal cord hemorrhage
• The patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment

Sponsors & Collaborators

• Dwight Owen: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

atezolizumab; Specimen Handling; Magnetic Resonance Spectroscopy; HhAntag691

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Dwight H Owen, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 25, 2024
• First Posted: September 27, 2024
• Study Start: December 31, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

US (1)