Atezolizumab Monotherapy and Consequent Therapy With Atezolizumab Plus Bevacizumab for NSCLC

Non Small Cell Lung Cancer Clinical Trial

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 Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03616691
• Other study ID #: 2018-05-170
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: August 1, 2018
• Est. completion date: June 30, 2020

Study information

• Verified date: August 2018
• Source: Samsung Medical Center
• Contact: Myung-Ju Ahn, PhD
• Phone: 82-2-3410-3438
• Email: silk.ahn[@]samsung.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 46
• Est. completion date: June 30, 2020
• Est. primary completion date: June 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

Drug:
• Atezolizumab
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)
• Bevacizumab
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Samsung Medical Center

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	about 36 months
Secondary	Best overall response rate	Best overall response rate	about 36 months
Secondary	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	about 36 months
Secondary	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	about 36 months
Secondary	Overall survival	OS, defined as the time from the first administration of atezolizumab and bevacizumab to death from any cause	about 36 months
Secondary	Adverse events (AEs)	Adverse events will be measured by the CTCAE scale, version 4.0	about 36 months