Trial Title:
Vismodegib and Atezolizumab for the Treatment of Recurrent or Metastatic Non-Small Cell Lung Cancer
NCT ID:
NCT06616623
Condition:
Metastatic Lung Non-Small Cell Carcinoma
Recurrent Lung Non-Small Cell Carcinoma
Stage IV Lung Cancer AJCC V8
Conditions: Official terms:
Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Atezolizumab
Antibodies, Monoclonal
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Atezolizumab
Description:
Given IV
Arm group label:
Treatment (vismodegib, atezolizumab)
Other name:
MPDL 3280A
Other name:
MPDL 328OA
Other name:
MPDL-3280A
Other name:
MPDL3280A
Other name:
MPDL328OA
Other name:
RG 7446
Other name:
RG-7446
Other name:
RG7446
Other name:
RO 5541267
Other name:
RO-5541267
Other name:
RO5541267
Other name:
Tecentriq
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo tissue and blood sample collection
Arm group label:
Treatment (vismodegib, atezolizumab)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (vismodegib, atezolizumab)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (vismodegib, atezolizumab)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Drug
Intervention name:
Vismodegib
Description:
Given PO
Arm group label:
Treatment (vismodegib, atezolizumab)
Other name:
Erivedge
Other name:
GDC 0449
Other name:
GDC-0449
Other name:
GDC0449
Other name:
Hedgehog Antagonist GDC-0449
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.
Detailed description:
PRIMARY OBJECTIVE:
I. To determine the safety and tolerability of the combination of vismodegib and
atezolizumab in patients with advanced NSCLC based upon the Common Terminology Criteria
for Adverse Events (CTCAE) version 5 criteria.
SECONDARY OBJECTIVE:
I. To determine the efficacy of the combination of vismodegib and atezolizumab in
patients with advanced NSCLC, including progression-free survival (PFS), objective
response (ORR), disease control rate (DCR), and overall survival (OS) based on modified
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
EXPLORATORY OBJECTIVE:
I. To study the effect of vismodegib on the levels of M2-TAMs and CD8+ T cells within the
tumor microenvironment (TME) as well as myeloid-derived suppressor cells (MDSCs) in
peripheral blood of study patients.
OUTLINE:
Patients receive vismodegib orally (PO) daily on days 1-28 and atezolizumab intravenously
(IV) on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease
progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or
magnetic resonance imaging (MRI) and blood sample collection throughout the study. Some
patients undergo tissue sample collection during screening and on study.
After completion of study treatment, patients are followed up every 12 weeks.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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
- Both values must be in the specified range
- Alkaline phosphatase (ALP) ≤ 2.5 x ULN with the following exceptions:
- Patients with documented liver or bone metastases: ALP ≤ 5 x ULN
- Albumin ≥ 2.5 g/dL
- International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN unless
subject is receiving anticoagulant therapy
- As long as PT or partial thromboplastin time (PTT) is within therapeutic range
of intended use of anticoagulants
- Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless subject is receiving
anticoagulant therapy
- As long as PT or PTT is within therapeutic range of intended use of
anticoagulants
- Anticipated life expectancy of ≥ 3 months
- Willing to comply with study procedures
- Female subject of childbearing potential will have a serum pregnancy test at
screening. Urine pregnancy tests will be performed at specified subsequent visits.
If a urine pregnancy test is positive, it must be confirmed by a serum pregnancy
test
- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods, and agreement to refrain
from donating eggs, as defined below:
- Women must remain abstinent or use contraceptive methods with a failure rate of
< 1% per year during the treatment period and for 5 months after the final
dose of atezolizumab and 24 months after the final dose of vismodegib. Women
must refrain from donating eggs during this same period
- A woman is considered to be of childbearing potential if she is postmenarchal,
has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea
with no identified cause other than menopause), and has not undergone surgical
sterilization (removal of ovaries and/or uterus). The definition of
childbearing potential may be adapted for alignment with local guidelines or
requirement
- Examples of contraceptive methods with a failure rate of < 1% per year
include bilateral tubal ligation, male sterilization, hormonal contraceptives
that inhibit ovulation, hormone-releasing intrauterine devices, and copper
intrauterine devices
- The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
postovulation methods) and withdrawal are not adequate methods of contraception
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or
use contraceptive measures, and agreement to refrain from donating sperm, for 5
months from last atezolizumab dose and 24 months after the final dose of vismodegib,
as defined below:
- With a female partner of childbearing potential or pregnant female partner, men
must remain abstinent or use a condom during the treatment period and, for 5
months from last atezolizumab dose and 24 months after the final dose of
vismodegib to avoid exposing the embryo. Men must refrain from donating sperm
during this same period
- The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
postovulation methods) and withdrawal are not adequate methods of preventing
drug exposure
- Be willing and able to understand and sign the written informed consent document
- Availability of a recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue
block. A recently obtained archival FFPE tumor tissue block (if an FFPE tissue block
cannot be provided, 15 unstained slides (10 minimum) will be acceptable) from a
primary or metastatic tumor resection or biopsy can be provided if it was obtained
within 1 year of trial screening
- Be willing to provide tissue from an on-treatment fine needle aspiration (FNA) or
core biopsy of a tumor lesion. Subjects must consent to on-treatment biopsy prior to
initiation of clinical trial, however subjects for whom newly-obtained samples
cannot be provided (e.g. inaccessible or subject safety concern) may still continue
on study
- Negative HIV test at screening with the following exception: patients with a
positive HIV test at screening are eligible provided they are stable on
anti-retroviral therapy, have a CD4 count > 200/uL, and have an undetectable
viral load
- Negative total hepatitis B core antibody (HBcAb) test at screening. For patients
with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must
be undetectable on suppressive therapy, if indicated
- Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV
antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening
- The HCV RNA test must be performed for patients who have a positive HCV
antibody test
Exclusion Criteria:
- 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
- The patient has no ongoing requirement for corticosteroids as therapy for
CNS disease
- If the patient is receiving anti-convulsant therapy, the dose is
considered stable
- Pregnancy or breastfeeding or intention of becoming pregnant during study treatment
or within 5 months for atezolizumab or within 24 months after the final dose of
vismodegib.
- Women of childbearing potential must have a negative serum pregnancy test
result within 14 days prior to initiation of study treatment
- Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
subject's participation for the full duration of the trial, or is not in the best
interest of the subject to participate, in the opinion of the treating investigator
- Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding that contraindicates the use of an investigational drug, may
affect the interpretation of the results, or may render the patient at high risk
from treatment complications
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
active pneumonitis on screening chest computed tomography (CT) scan. History of
radiation pneumonitis in the radiation field (fibrosis) is permitted
- Known active tuberculosis (specific testing is only needed if clinically indicated)
- Significant cardiovascular disease (such as New York Heart Association Class II or
greater cardiac disease, myocardial infarction, or cerebrovascular accident) within
3 months prior to initiation of study treatment, unstable arrhythmia, or unstable
angina
- Major surgical procedure, other than for diagnosis, within 4 weeks prior to
initiation of study treatment, or anticipation of need for a major surgical
procedure during the study
- Patients with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of
the investigational regimen are eligible for this trial
- Severe infection within 4 weeks prior to initiation of study treatment, including,
but not limited to, hospitalization for complications of infection, bacteremia, or
severe pneumonia, or any active infection that could impact patient safety
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation
of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a
urinary tract infection or chronic obstructive pulmonary disease exacerbation) are
eligible for the study
- Prior allogeneic stem cell or solid organ transplantation
- Live, attenuated vaccines (e.g., FluMist®) are prohibited within 4 weeks prior to
initiation of study treatment, during treatment with atezolizumab, and for 5 months
after the last dose of atezolizumab
- Treatment with systemic immunostimulatory agents (including, but not limited to,
interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug
(whichever is longer) prior to initiation of study treatment
- History of severe allergic anaphylactic reactions to chimeric or humanized
antibodies or fusion proteins
- Known hypersensitivity to Chinese hamster ovary cell products or to any component of
the atezolizumab formulation
- Any patient who experience unacceptable toxicity on prior checkpoint inhibitor
therapy:
- ≥ grade 3 adverse event (AE) related to checkpoint inhibitor
- ≥ grade 2 immune-related AE associated with checkpoint inhibitor
- CNS, ocular or cardiac AE of any grade related to checkpoint inhibitor
- NOTE: Patients with a prior endocrine AE are permitted to enroll if they
are stably maintained on appropriate replacement therapy and are
asymptomatic
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Contact:
Last name:
Dwight H. Owen, MD
Phone:
614-293-6786
Email:
Dwight.Owen@osumc.edu
Contact backup:
Last name:
Dwight H. Owen, MD
Start date:
December 1, 2024
Completion date:
December 31, 2026
Lead sponsor:
Agency:
Dwight Owen
Agency class:
Other
Collaborator:
Agency:
Genentech, Inc.
Agency class:
Industry
Source:
Ohio State University Comprehensive Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06616623
http://cancer.osu.edu
