Subjects with EGFR mutation, T790M negative NSCLC who failed first line (1L) EGFR TKI therapy MedDRA version: 20.0 Level: PT Classification code 10029515 Term: Non-small cell lung cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed Written Informed Consent 2. Target Population a) Eastern Cooperative Group (ECOG) Performance Status 0-1 b) Subjects with histologically confirmed Stage IV or recurrent EGFR MT+ (ie, G719X, L861Q, Del 19, and L858R) NSCLC (per the 7th International Association for the Study of Lung Cancer classification)37 with disease progression on therapy with 1 prior EGFR TKI therapy consisting of erlotinib, afatinib, or gefitinib c) No evidence of exon 20 T790M mutation detected by tumor or cfDNA analysis obtained at progression on prior EGFR TKI therapy. T790M testing will be confirmed centrally using the cobas® EGFR Mutation Test v2 (US-IVD). d) Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) e) No prior systemic therapy for advanced or metastatic NSCLC, except for 1 prior line of first- or second-generation EGFR TKI. Prior adjuvant or neoadjuvant chemotherapy for early stage lung cancer is permitted as long as all toxicities have resolved or stabilized. i) Prior 1L EGFR TKI therapy must have been completed at least 2 weeks prior to randomization ii) Switch between first- or second-generation EGFR TKI due to toxicity with no evidence of disease progression is acceptable and will not be multiple lines of EGFR therapy. Further questions regarding eligibility of subjects with short-term 1L TKI treatment should be directed to the Medical Monitor. f) Subjects must have sample available for PD-L1 IHC and exon 20 T790M testing performed by the central lab during the screening period i) Either a formalin-fixed, paraffin-embedded (FFPE) tissue block or unstained tumor tissue sections, with an associated pathology report, must be submitted for biomarker evaluation prior to randomization. The tumor tissue sample may be fresh or archival if obtained within 6 months prior to enrollment, and there can have been no systemic therapy (eg, adjuvant or neoadjuvant chemotherapy) given after the sample was obtained. ii) Tissue must be a core needle biopsy, excisional, or incisional biopsy. Fine needle biopsies or drainage of pleural effusions with cytospins are not considered adequate for biomarker review and randomization. Biopsies of bone lesions that do not have a soft tissue component or decalcified bone tumor samples are also not acceptable g) Prior palliative radiotherapy to non-CNS lesions must have been completed at least 2 weeks prior to randomization. Subjects with symptomatic tumor lesions at baseline that may require palliative radiotherapy within 4 weeks of randomization are strongly encouraged to receive palliative radiotherapy prior to randomization h) Screening laboratory values must meet the following criteria (using CTCAE v4): i) WBC = 2000/uL ii) Neutrophils =1500/uL iii) Platelet = 100x103/uL iv) Hemoglobin = 9.0 g/dL v) Serum creatinine = 1.5 x ULN or calculated creatinine clearance ? 50 mL/min (using the Cockcroft Gault formula) Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/ dL Male CrCl = (140 - age in years) x weight in kg x 1.0 72 x serum creatinine in mg/ dL vi) AST = 3.0 x ULN vii) ALT = 3.0 x ULN viii) Total Bilirubin = 1.5 x ULN (except subjects with Gilbert Syndrome who must have a total bilirubin level of < 3.0 x ULN) h) Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to ra
Exclusion criteria
Exclusion criteria: 1. Target Disease Exceptions a) Subjects with known EGFR mutation, T790M positive, detected by tumor or cfDNA analysis b) Subjects with known ALK translocations which are sensitive to available targeted inhibitor therapy are excluded. If tested, use of an FDA-approved test is strongly encouraged. Subjects with unknown or indeterminate ALK status may be enrolled. d) Subjects with carcinomatous meningitis f) Subjects with known SCLC transformation g) Subjects who have progressed within 3 months of 1L EGFR TKI. 2. Medical History and Concurrent Diseases a) Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before randomization. b) Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast. c) Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. d) Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. e) Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity. g) Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be performed at sites where mandated locally h) HBV carriers or those subjects receiving antiviral treatment of hepatitis B virus (HBV) or hepatitis C virus (HCV) i) Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways 3. Physical and Laboratory Test Findings a) Subjects with = Grade 2 peripheral neuropathy b) Subjects with active hepatitis B (positive hepatitis B surface antigen [HBsAg]) or HCV (hepatitis C virus) [positive HCV RNA]) i) Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg) are eligible. HBV DNA must be obtained in these patients prior to randomization. HBV carriers or those patients requiring antiviral therapy are not eligible to participate. ii) Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA. 4. Allergies and Adverse Drug Reaction a) History of allergy or hypersensitivity to platinum-containing compounds or other study drug component 5. Other Exclusion Criteria a) Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a subject. Strict conditions apply and Bristol-Myers Squibb approval is required). b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious dise
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the Progression Free Survival by BICR(blinded independent central review) of nivolumab plus pemetrexed/platinum and nivolumab plus ipilimumab compared to pemetrexed plus platinum in EGFR mutation positive (ie, G719X, L861Q, Del 19, and L858R), T790M negative metastatic or locally advanced NSCLC that has progressed on 1L EGFR TKI;Secondary Objective: To determine the OS of nivolumab plus pemetrexed/platinum or nivolumab plus ipilimumab compared to pemetrexed plus platinum in EGFR mutation positive (ie, G719X, L861Q, Del 19, and L858R), T790M negative metastatic or locally advanced NSCLC whose tumor has progressed on 1L EGFR TKI To determine the ORR per RECIST 1.1 by BICR, the duration of response (DOR) by BICR, and the 9-month and 12-month PFS rates by BICR of nivolumab plus pemetrexed/platinum or nivolumab plus ipilimumab compared to pemetrexed plus platinum in EGFR mutation positive (ie, G719X, L861Q, Del 19, and L858R), T790M negative metastatic or locally advanced NSCLC that has progressed on 1L EGFR TKI;Primary end point(s): The primary endpoint is PFS (based on BICR assessment) in all randomized subjects. PFS is defined as the time between the date of randomization and the first date of documented progression, as determined by BICR, or death, whichever occurs first;Timepoint(s) of evaluation of this end point: 20 months of accrual period followed by additional 13 months follow-up | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints of the study are: 1. OS(time between the date of randomization and the date of death) 2. ORR per RECIST 1.1 (the number of subjects with a BOR of CR or PR divided by the number of randomized subjects for each treatment group) based on BICR assessment. The BOR is defined as the best response designation, as determined by BICR, recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of subsequent anti-cancer therapy, whichever occurs first 3. DOR by BICR and the 9-month and 12-month PFS rates by BICR. DOR is defined as the time between the date of first confirmed response to the date of the first documented tumor progression (per RECIST 1.1) by BICR or death;Timepoint(s) of evaluation of this end point: Radiographic assessment at Week 7, then every 6 weeks (± 7 days) for the first 12 months (until Week 49) and every 12 weeks (± 7 days) thereafter, to determine changes in tumor size. RECIST 1.1 criteria will be used for the assessment Pharmacokinetics (PK) and Immunogenicity Sample Collection for Arm A(1 Cycle = 3 Weeks) and Arm B(1 Cycle = 2 weeks) respectively | — |
Countries
China, France, Hong Kong, Japan, Korea, Republic of, Singapore, Spain, Taiwan
Contacts
Public ContactGCT-SU
Bristol-Myers Squibb International Corporation
Outcome results
None listed