Clinical Trials /

Atezolizumab Monotherapy and Consequent Therapy With Atezolizumab Plus Bevacizumab for NSCLC

NCT03616691

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 2018-05-170
  • NCT ID: NCT03616691

Conditions

  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
AtezolizumabAtezolizumab
BevacizumabAtezolizumabAtezolimab+Bevacizumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
AtezolizumabExperimentalThe dose level of atezolizumab proposed to be tested in this study is 1200 mg administered by IV infusion every 3 weeks (q3w)
  • Atezolizumab
Atezolimab+BevacizumabExperimentalOnce 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.
  • Atezolizumab
  • Bevacizumab

Eligibility Criteria

        Inclusion Criteria:

        Patients must meet all of the following criteria to be eligible for study entry:

          1. Signed Informed Consent Form

          2. Ability to comply with protocol

          3. 20 years old or older

          4. Histologically confirmed stage IIIb, IV or recurrent non-squamous cell NSCLC

          5. Baseline and repeat biopsy at the time of progression is mandatory. Repeat biopsy at
             progression to atezolizumab with bevacizumab is optional.

          6. 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.

          7. ECOG performance status of 0 to 1

          8. At least one measurable lesion by RECIST v1.1

          9. 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.

         10. 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.

          1. Prior treatment with anti-PD1 or anti-PDL1 inhibitors

          2. Patients with a known hypersensitivity to atezolizumab and/or bevacizumab or any of
             the excipients.

          3. History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanized antibodies or fusion proteins.

          4. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster
             ovary cells.

          5. Patients with a sensitizing EGFR mutation

          6. Patients with a previously detected ALK fusion oncogene

          7. 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

          8. Active autoimmune disease requiring systemic treatment within the past 3 months or a
             documented history of clinically severe autoimmune disease

          9. Evidence of interstitial lung disease or active, non-infectious pneumonitis

         10. Has received a live vaccine within 30 days prior to the first dose of trial treatment

         11. Has a known history of Human Immunodeficieny Virus (HIV)

         12. Has known active Hepatitis B (e.g. HBsAg reactive) or Hepatitis C (e.g. HCV RNA is
             detected)

         13. Surgery undertaken less than 4 weeks before the study

         14. Localized radiotherapy unless completed more than 2 weeks before the study

         15. Uncontrolled systemic illness such as DM, CHF, unstable angina, hypertension or
             arrhythmia

         16. Pregnant or breastfeeding or lactating female patients

         17. 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

         18. Uncontrolled symptomatic brain metastasis

         19. 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

         20. 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.

         21. Prior history of hypertensive crisis or hypertensive encephalopathy

         22. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or
             recent peripheral arterial thrombosis) within 6 months prior to randomization

         23. History of hemoptysis (>,=one-half teaspoon of bright red blood per episode) within 1
             month prior to randomization

         24. Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic
             anticoagulation)

         25. Current or recent (within 10 days of Atezolizumab administration use of aspirin (>325
             mg/day) or treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol

         26. 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

         27. Core biopsy or other minor surgical procedure, excluding placement of a vascular
             access device, within 7 days prior to the first dose of bevacizumab

         28. History of abdominal or tracheosphageal fistula or gastrointestinal perforation within
             6 months prior to randomization

         29. Clinical signs of gastrointestinal obstruction or requirement for routine parenteral
             hydration, parenteral nutrition, or tube feeding

         30. Evidence of abdominal free air not explained by paracentesis or recent surgical
             procedure

         31. Serious, non-healing wound, active ulcer, or untreated bone fracture

         32. 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.

         33. Clear tumor infiltration into the thoracic great vessels is seen on imaging

         34. Clear cavitation of pulmonary lesions is seen on imaging
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The primary objective for this study is to evaluate efficacy of atezolizumab with bevacizumab after radiologically progress of atezolizumab monotherapy
Time Frame:about 36 months
Safety Issue:
Description:measured by disease control rate (DCR) per investigator using RECIST v1.1

Secondary Outcome Measures

Measure:Best overall response rate
Time Frame:about 36 months
Safety Issue:
Description:Best overall response rate
Measure:Progression-free survival
Time Frame:about 36 months
Safety Issue:
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
Measure:Duration of response
Time Frame:about 36 months
Safety Issue:
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
Measure:Overall survival
Time Frame:about 36 months
Safety Issue:
Description:OS, defined as the time from the first administration of atezolizumab and bevacizumab to death from any cause
Measure:Adverse events (AEs)
Time Frame:about 36 months
Safety Issue:
Description:Adverse events will be measured by the CTCAE scale, version 4.0

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Samsung Medical Center

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