Atezolizumab Monotherapy and Consequent Therapy With Atezolizumab Plus Bevacizumab for NSCLC
Primary Purpose
Non Small Cell Lung Cancer
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Atezolizumab
Bevacizumab
Sponsored by
About this trial
This is an interventional treatment trial for Non Small Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria:
Patients must meet all of the following criteria to be eligible for study entry:
- Signed Informed Consent Form
- Ability to comply with protocol
- 20 years old or older
- Histologically confirmed stage IIIb, IV or recurrent non-squamous cell NSCLC
- Baseline and repeat biopsy at the time of progression is mandatory. Repeat biopsy at progression to atezolizumab with bevacizumab is optional.
- Disease progression during or following treatment with a prior platinum-containing regimen for locally advanced, unresectable/inoperable or metastatic NSCLC or disease recurrence within 6 months of treatment with a platinum-based adjuvant/neoadjuvant regimen or combined modality (e.g.,chemoradiation) regimen with curative intent.
- ECOG performance status of 0 to 1
- At least one measurable lesion by RECIST v1.1
- Patients with brain metastasis may be enrolled provided they are asymptomatic requiring no treatment, or are asymptomatic following therapy such as surgery, WBRT or SRT.
- Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment:
Exclusion Criteria:
Patients who meet any of the following criteria will be excluded from study entry.
- Prior treatment with anti-PD1 or anti-PDL1 inhibitors
- Patients with a known hypersensitivity to atezolizumab and/or bevacizumab or any of the excipients.
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
- Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells.
- Patients with a sensitizing EGFR mutation
- Patients with a previously detected ALK fusion oncogene
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease
- Evidence of interstitial lung disease or active, non-infectious pneumonitis
- Has received a live vaccine within 30 days prior to the first dose of trial treatment
- Has a known history of Human Immunodeficieny Virus (HIV)
- Has known active Hepatitis B (e.g. HBsAg reactive) or Hepatitis C (e.g. HCV RNA is detected)
- Surgery undertaken less than 4 weeks before the study
- Localized radiotherapy unless completed more than 2 weeks before the study
- Uncontrolled systemic illness such as DM, CHF, unstable angina, hypertension or arrhythmia
- Pregnant or breastfeeding or lactating female patients
- Female participants of childbearing potential will not agree to use to highly effective form(s) of contraception (i.e., one that results in a low failure rate [<1% per year] when used consistently and correctly) during the treatment period and to continue its use for 5 months after the last dose of Atezolizumab
- Uncontrolled symptomatic brain metastasis
- Prior history of malignancy within 5 years from study entry except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer, well-treated thyroid cancer
- Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg) Anti-hypertensive therapy to achieve these parameters is allowable.
- Prior history of hypertensive crisis or hypertensive encephalopathy
- Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to randomization
- History of hemoptysis (>,=one-half teaspoon of bright red blood per episode) within 1 month prior to randomization
- Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
- Current or recent (within 10 days of Atezolizumab administration use of aspirin (>325 mg/day) or treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol
- Current use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes that has not been stable for >2 weeks prior to randomization
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to the first dose of bevacizumab
- History of abdominal or tracheosphageal fistula or gastrointestinal perforation within 6 months prior to randomization
- Clinical signs of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding
- Evidence of abdominal free air not explained by paracentesis or recent surgical procedure
- Serious, non-healing wound, active ulcer, or untreated bone fracture
- Proteinuria, as demonstrated by urine dipstick or >1.0 g of protein in a 24-hour urine collection All patients with >, =2+ protein on dipstick urinalysis at baseline must undergo a 24 hour urine collection and must demonstrate > 1 g of protein in 24 hours.
- Clear tumor infiltration into the thoracic great vessels is seen on imaging
- Clear cavitation of pulmonary lesions is seen on imaging
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Atezolizumab
Atezolimab+Bevacizumab
Arm Description
The dose level of atezolizumab proposed to be tested in this study is 1200 mg administered by IV infusion every 3 weeks (q3w)
Once radiologic progression confirmed from atezolizumab monotherapy (stage 1), 1200mg of atezolizumab would be administered with 15mg/kg of bevacizumab as combination therapy (stage 2). Both of drugs are administered via intravenous infusion every 3 weeks.
Outcomes
Primary Outcome Measures
The primary objective for this study is to evaluate efficacy of atezolizumab with bevacizumab after radiologically progress of atezolizumab monotherapy
measured by disease control rate (DCR) per investigator using RECIST v1.1
Secondary Outcome Measures
Best overall response rate
Best overall response rate
Progression-free survival
PFS, defined as the time from the first administration of atezolizumab and bevacizumab to the first occurrence of disease progression as determined by investigator using RECIST v1.1 or death from any cause, whichever comes first
Duration of response
DOR, defined as the time from first occurrence of a documented objective response to the time of disease progression as determined by the investigator using RECIST v1.1 or death from any cause, whichever comes first
Overall survival
OS, defined as the time from the first administration of atezolizumab and bevacizumab to death from any cause
Adverse events (AEs)
Adverse events will be measured by the CTCAE scale, version 4.0
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03616691
Brief Title
Atezolizumab Monotherapy and Consequent Therapy With Atezolizumab Plus Bevacizumab for NSCLC
Official Title
A Phase II Single-arm Trial of Atezolizumab Monotherapy and Consequent Therapy With Atezolizumab Plus Bevacizumab in Patients With Non-Small Cell Lung Cancer After Failure With Platinum-Containing Chemotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Unknown status
Study Start Date
August 1, 2018 (Anticipated)
Primary Completion Date
June 30, 2020 (Anticipated)
Study Completion Date
June 30, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Samsung Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a single-arm phase II trial to evaluate the efficacy and safety of atezolizumab and bevacizumab combination therapy (stage 2) after radiologic progression of atezolizumab monotherapy (stage 1) in Korean patients with locally advanced or metastatic NSCLC who have progressed during or following a platinum-containing regimen. Initially, patients will be treated with Atezolizumab 1200mg every 3 weeks as a single agent (stage 1). After radiologic progression from atezolizumab monotherapy, patients will be consequently treated with atezolizumab (1200mg every 3 weeks) and combination with bevacizumab (15mg/kg every 3 weeks). Exploratory biomarkers will be observed in order to identify predictive biomarkers correlated to response and to evaluate the changes of local and systemic immune profile between baseline and at the time of progression.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Small Cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
46 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Atezolizumab
Arm Type
Experimental
Arm Description
The dose level of atezolizumab proposed to be tested in this study is 1200 mg administered by IV infusion every 3 weeks (q3w)
Arm Title
Atezolimab+Bevacizumab
Arm Type
Experimental
Arm Description
Once radiologic progression confirmed from atezolizumab monotherapy (stage 1), 1200mg of atezolizumab would be administered with 15mg/kg of bevacizumab as combination therapy (stage 2). Both of drugs are administered via intravenous infusion every 3 weeks.
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Intervention Description
Stage I: The dose level of atezolizumab proposed to be tested in this study is 1200 mg administered by IV infusion every 3 weeks (q3w)
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Atezolizumab
Intervention Description
Stage II: Once radiologic progression confirmed from atezolizumab monotherapy (stage 1), 1200mg of atezolizumab would be administered with 15mg/kg of bevacizumab as combination therapy every 3 weeks.
Primary Outcome Measure Information:
Title
The primary objective for this study is to evaluate efficacy of atezolizumab with bevacizumab after radiologically progress of atezolizumab monotherapy
Description
measured by disease control rate (DCR) per investigator using RECIST v1.1
Time Frame
about 36 months
Secondary Outcome Measure Information:
Title
Best overall response rate
Description
Best overall response rate
Time Frame
about 36 months
Title
Progression-free survival
Description
PFS, defined as the time from the first administration of atezolizumab and bevacizumab to the first occurrence of disease progression as determined by investigator using RECIST v1.1 or death from any cause, whichever comes first
Time Frame
about 36 months
Title
Duration of response
Description
DOR, defined as the time from first occurrence of a documented objective response to the time of disease progression as determined by the investigator using RECIST v1.1 or death from any cause, whichever comes first
Time Frame
about 36 months
Title
Overall survival
Description
OS, defined as the time from the first administration of atezolizumab and bevacizumab to death from any cause
Time Frame
about 36 months
Title
Adverse events (AEs)
Description
Adverse events will be measured by the CTCAE scale, version 4.0
Time Frame
about 36 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must meet all of the following criteria to be eligible for study entry:
Signed Informed Consent Form
Ability to comply with protocol
20 years old or older
Histologically confirmed stage IIIb, IV or recurrent non-squamous cell NSCLC
Baseline and repeat biopsy at the time of progression is mandatory. Repeat biopsy at progression to atezolizumab with bevacizumab is optional.
Disease progression during or following treatment with a prior platinum-containing regimen for locally advanced, unresectable/inoperable or metastatic NSCLC or disease recurrence within 6 months of treatment with a platinum-based adjuvant/neoadjuvant regimen or combined modality (e.g.,chemoradiation) regimen with curative intent.
ECOG performance status of 0 to 1
At least one measurable lesion by RECIST v1.1
Patients with brain metastasis may be enrolled provided they are asymptomatic requiring no treatment, or are asymptomatic following therapy such as surgery, WBRT or SRT.
Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment:
Exclusion Criteria:
Patients who meet any of the following criteria will be excluded from study entry.
Prior treatment with anti-PD1 or anti-PDL1 inhibitors
Patients with a known hypersensitivity to atezolizumab and/or bevacizumab or any of the excipients.
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells.
Patients with a sensitizing EGFR mutation
Patients with a previously detected ALK fusion oncogene
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
Active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease
Evidence of interstitial lung disease or active, non-infectious pneumonitis
Has received a live vaccine within 30 days prior to the first dose of trial treatment
Has a known history of Human Immunodeficieny Virus (HIV)
Has known active Hepatitis B (e.g. HBsAg reactive) or Hepatitis C (e.g. HCV RNA is detected)
Surgery undertaken less than 4 weeks before the study
Localized radiotherapy unless completed more than 2 weeks before the study
Uncontrolled systemic illness such as DM, CHF, unstable angina, hypertension or arrhythmia
Pregnant or breastfeeding or lactating female patients
Female participants of childbearing potential will not agree to use to highly effective form(s) of contraception (i.e., one that results in a low failure rate [<1% per year] when used consistently and correctly) during the treatment period and to continue its use for 5 months after the last dose of Atezolizumab
Uncontrolled symptomatic brain metastasis
Prior history of malignancy within 5 years from study entry except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer, well-treated thyroid cancer
Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg) Anti-hypertensive therapy to achieve these parameters is allowable.
Prior history of hypertensive crisis or hypertensive encephalopathy
Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to randomization
History of hemoptysis (>,=one-half teaspoon of bright red blood per episode) within 1 month prior to randomization
Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
Current or recent (within 10 days of Atezolizumab administration use of aspirin (>325 mg/day) or treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol
Current use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes that has not been stable for >2 weeks prior to randomization
Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to the first dose of bevacizumab
History of abdominal or tracheosphageal fistula or gastrointestinal perforation within 6 months prior to randomization
Clinical signs of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding
Evidence of abdominal free air not explained by paracentesis or recent surgical procedure
Serious, non-healing wound, active ulcer, or untreated bone fracture
Proteinuria, as demonstrated by urine dipstick or >1.0 g of protein in a 24-hour urine collection All patients with >, =2+ protein on dipstick urinalysis at baseline must undergo a 24 hour urine collection and must demonstrate > 1 g of protein in 24 hours.
Clear tumor infiltration into the thoracic great vessels is seen on imaging
Clear cavitation of pulmonary lesions is seen on imaging
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Myung-Ju Ahn, PhD
Phone
82-2-3410-3438
Email
silk.ahn@samsung.com
First Name & Middle Initial & Last Name or Official Title & Degree
hyunjung Shin
Phone
82-70-7014-6763
Email
hjds.shin@samsung.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Myung-Ju Ahn, PhD
Organizational Affiliation
Samsung Medical Center
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
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Atezolizumab Monotherapy and Consequent Therapy With Atezolizumab Plus Bevacizumab for NSCLC
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