metastatic squamous NSCLC MedDRA version: 21.1 Level: PT Classification code 10023775 Term: Large cell lung cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10001245 Term: Adenosquamous cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10001247 Term: Adenosquamo
Conditions
Sponsors
Merck Sharp & Dohme LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The subject must: 1. Have a histologically or cytologically confirmed diagnosis of stage IV (M1a or M1b-AJCC 7th edition) squamous NSCLC. Patients with mixed histology (example adenosquamous) are allowed if there is squamous component in the specimen. 2. Have measurable disease based on RECIST 1.1 as determined by the local site investigator/radiology assessment. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 3. Have not received prior systemic treatment for their metastatic NSCLC. Subjects who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the development of metastatic disease. 4. Have provided tumour tissue from locations not radiated prior to biopsy; formalin- fixed specimens after the subject has been diagnosed with metastatic disease will be preferred for determination of PD-L1 status prior to randomization. Biopsies obtained prior to receipt of adjuvant/neoadjuvant chemotherapy will be permitted if recent biopsy is not feasible. 5. Be =18 years of age on day of providing documented informed consent. 6. Have a life expectancy of at least 3 months. 7. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status. 8. Have adequate organ function as indicated by the, 'Adequate Organ Function Laboratory Values Algorithm' within the protocol 9. If female of childbearing potential , have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 10. If female of childbearing potential, be willing to use an adequate method of contraception as outlined in the protocol, for the course of the study through 180 days after the last dose of study medication Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. 11. If male subject with a female partner(s) of child-bearing potential, must agree to use an adequate method of contraception as outlined in the protocol, starting with the first dose of study therapy through 95 days after the last dose of study therapy. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. 12. Subject (or legally acceptable representative) has provided documented informed consent/assent for the trial. The subject may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 400 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 160
Exclusion criteria
Exclusion criteria: Subject must be excluded if subject: 1. Has non-squamous histology NSCLC. Mixed tumours will be categorized by the predominant cell type; if small cell elements are present, the subject is ineligible; for non-small cell histology if there is any squamous element is present (example adenosquamous), the subject is eligible; the squamous element does not have to be predominant. 2. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to administration of pembrolizumab. 3. Before the first dose of trial treatment: a) Has received prior systemic cytotoxic chemotherapy for metastatic disease b) Has received other targeted or biological antineoplastic therapy (e.g., erlotinib, crizotinib, cetuximab) for metastatic disease c) Had major surgery ( 30 Gy within 6 months of the first dose of trial treatment. 5. Completed palliative radiotherapy within 7 days of the first dose of trial treatment. 6. Is expected to require any other form of antineoplastic therapy while on study. 7. Has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted. 8. Has a known history of prior malignancy except if the subject has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy 9. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are clinically stable for at least 2 weeks and, have no evidence of new or enlarging brain metastases and also are off steroids 3 days prior to dosing with study medication. Stable brain metastases by this definition should be established prior to the first dose of study medication. Subjects with asymptomatic brain metastases (i.e., no neurological symptoms, no requirements for corticosteroids, and no lesion >1.5 cm) may participate but will require regular imaging of the brain as a site of disease. 10. Has pre-existing peripheral neuropathy that is = Grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) version 4 criteria. 11. Previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody. 12. Has a known sensitivity to any component of carboplatin or paclitaxel or nabpaclitaxel. 13. Has active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 14. Is on chronic systemic steroids. Subjects with asthma that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study. 15. Had prior treatment with any other anti-PD-1, or PD-L1 or PD-L2 agent or an antibody or a small molecule targeting other immuno-regulatory receptors or mechanisms. Has participated in any other pembrolizumab trial and has been treated with pembrolizumab. Examples of such antibodies include (but are not limited to) antibodies against IDO, PD-L1, IL-2R
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: In subjects with metastatic squamous non-small cell lung cancer (NSCLC) receiving investigator’s choice of standard of care chemotherapy (i.e. carboplatin and a taxane): 1. To evaluate progression free survival (PFS) per RECIST 1.1 as assessed by a central imaging vendor in subjects treated with Pembrolizumab compared to placebo. 2. To evaluate overall survival (OS) in subjects treated with Pembrolizumab compared to placebo. ;Secondary Objective: In 1L subjects with metastatic squamous non-small cell lung cancer (NSCLC) receiving investigator’s choice of standard of care chemotherapy (i.e. carboplatin and a taxane): 1. To evaluate the objective response rate (ORR) and duration of response (DOR) per RECIST 1.1 as assessed by a central imaging vendor in subjects treated with Pembrolizumab compared to placebo. 2. To evaluate the safety and tolerability profile of Pembrolizumab.;Primary end point(s): 1) Progression-free Survival (PFS) per RECIST 1.1 assessed by a blinded independent central imaging vendor review 2) Overall survival (OS);Timepoint(s) of evaluation of this end point: IA1 Performed after ~ 200 subjects have had approximately 28 weeks of FU To demonstrate superiority of pembrolizumab + carboplatin and a taxane in ORR IA2 Performed after a target number of PFS events (~ 332) is observed To demonstrate 1)superiority of pembrolizumab + carboplatin and a taxane in PFS; 2) superiority of pembrolizumab + carboplatin and a taxane in OS IA3 Performed after a target number of PFS events (~415) is observed To demonstrate 1)superiority of pembrolizumab + carboplatin and a taxane in PFS; 2) superiority of pembrolizumab + carboplatin and a taxane in OS FA: ~ 361 deaths occurred Evaluation of OS Because of PFS and OS results at the 2IA, subsequent analyses will be conducted and reviewed by the SPONSOR and performed at 3IA and/or FA, or as needed. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) ORR (Objective response rates) per RECIST 1.1 by blinded independent central imaging vendor review 2) DOR (Duration of Response) per RECIST 1.1 by blinded independent central imaging vendor review 3) Safety as assessed by a variety of parameters of AEs;Timepoint(s) of evaluation of this end point: All secondary efficacy endpoints will be evaluated as part of the trial's interim and final analyses.Safety endpoints will be evaluated at each of time points specified for the primary efficacy endpoints. | — |
Countries
Australia, Canada, China, France, Germany, Hungary, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Russian Federation, Spain, Thailand, Turkey, United States
Contacts
Public ContactGCTO
Merck Sharp & Dohme LLC
Outcome results
None listed