A Phase III, open-label, multicenter trial of avelumab (MSB0010718C) versus platinum-based doublet as a first-line treatment of recurrent or Stage IV PD-L1+ non–small-cell lung cancer
- Conditions
- -C34 Malignant neoplasm of bronchus and lungMalignant neoplasm of bronchus and lungC34
- Registration Number
- PER-004-16
- Lead Sponsor
- Merck KGaA,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 8
1. Signed written informed consent before any trial-related procedure is undertaken that is not part of the standard patient management
2. Male or female subjects aged ≥ 18 years
3. Availability of a formalin-fixed, paraffin-embedded block containing tumor tissue or at least 7 (preferably 10) unstained tumor slides suitable for PD-L1 expression assessment
4. Tumor determined to be positive for PD-L1 expression per the evaluation of a central laboratory
5. At least 1 lesion that can be measured. A lesion that has been irradiated can be used as a measurable lesion providing that disease has progressed at that site
6. Subjects with histologically confirmed metastatic or recurrent NSCLC (per 7th International Association for the Study of Lung Cancer classification)
7. Patients must not have received any treatment for systemic lung cancer, including EGFR inhibitors or anaplastic lymphoma kinase (ALK) inhibitors
8. Patients could have received adjuvant chemotherapy or loco-regional treatment that included chemotherapy for locally advanced disease, as long as disease recurrence occurred at least 6 months after the completion of the last administration of chemotherapy
9. ECOG PS of 0 to 1 at trial entry
10. Estimated life expectancy of more than 12 weeks
11. Adequate hematological function defined by white blood cell (WBC) count ≥ 2.5 × 109/L with absolute neutrophil count (ANC) ≥ 1.5 × 109/L, lymphocyte count ≥ 0.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused)
12. Adequate hepatic function defined by a total bilirubin level ≤ 1.0 × the upper limit of normal (ULN) range and AST and alanine aminotransferase (ALT) levels ≤ 2.5 × ULN for all subjects
13. Adequate renal function defined by an estimated creatinine clearance ≥ 50 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
14. Negative blood pregnancy test at screening for women of childbearing potential. For the purposes of this trial, women of childbearing potential are defined as: All female subjects after puberty unless they are post-menopausal for at least two years, are surgically sterile or not sexually active”
15. Effective contraception for both male and female subjects if the risk of conception exists.
1. Subjects whose disease harbors an activating EGFR mutation. Subjects of unknown EGFR status will require testing for EGFR mutations (local laboratory, or central laboratory if local testing is not available) and must be determined to be EGFR wild-type to be eligible for this trial
2. Subjects with non-squamous cell NSCLC whose disease harbors an ALK rearrangement. Subjects of unknown ALK status will require testing for ALK rearrangement (local laboratory, or central laboratory if local testing is not available) and must be determined to be ALK wild-type to be eligible for this trial
3. Prior therapy with any antibody or drug targeting T-cell coregulatory proteins, concurrent anticancer treatment, or immunosuppressive agents.
4. Concurrent anticancer treatment (for example, cytoreductive therapy, radiotherapy [with the exception of palliative bone-directed radiotherapy], immune therapy, or cytokine therapy except for erythropoietin)
5. Major surgery for any reason, except diagnostic biopsy, within 4 weeks of randomization and / or if the subject has not fully recovered from the surgery within 4 weeks of randomization
6. Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment (with the exception of subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to < 10 mg prednisone daily). Note:
a. Subjects receiving bisphosphonate or denosumab are eligible provided treatment was initiated at least 14 days before first dose of trial treatment
b. Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon is acceptable as long as it is anticipated that the administration of steroids will be completed in 14 days, or that the daily dose after 14 days will be ≤ 10 mg per day of equivalent prednisone
7. All subjects with brain metastases, except those meeting the following criteria:
a. Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrollment
b. No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
c. Subjects must be either off steroids or on a stable or decreasing dose of <10mg daily prednisone (or equivalent)
d. All potential exceptions must be discussed with the study Medical Monitor prior to enrollment
8. Previous malignant disease (other than NSCLC) within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or carcinoma in situ (bladder, cervical, colorectal, breast)
9. Prior organ transplantation, including allogeneic stem-cell transplantation
10. Significant acute or chronic infections including, among others:
•Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
•Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV antibody tested positive)
11. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:
a. Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
b. Subjects requiring hormone replacement with corticosteroids a
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method