MedDRA version: 20.0 Level: LLT Classification code 10066490 Term: Progression of non-small cell lung cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: Pembrolizumab
Product Code: MK-3475
Pharmaceutical Form: Powder for injection
INN or Proposed INN: Pembrolizumab
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Other descriptive
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., (Merck)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Be willing and able to provide written informed consent/assent for the trial. 2) Be =18 years of age on day of signing informed consent. 3) Have a life expectancy of at least 3 months. 4) Have a histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) and have at least one measurable lesion as defined by RECIST 1.1. The target lesion(s) should also have bi-dimensional measurability for irRC evaluation on study. 5) Have experienced investigator determined radiographic progression per RECIST 1.1 of NSCLC after treatment with at least two cycles of a platinum-containing doublet for stage IIIB/IV or recurrent disease. The site’s study team must have reviewed pre-trial images that are of diagnostic quality from at least 2 dates to determine that radiographic progression has occurred per RECIST 1.1 following initiation of the first-line platinum-containing doublet. A platinum-containing doublet is defined as a platinum-based cytotoxic systemic agent administered in the same cycle as another cytotoxic systemic chemotherapeutic agent. The central imaging vendor must have received these scans and have confirmed that they are of acceptable diagnostic quality prior to randomization in this trial for a possible retrospective analysis of this eligibility criterion. The central vendor will not be confirming eligibility prior to randomization. Completion of treatment with a platinum-containing doublet as adjuvant therapy within one year of signing informed consent will satisfy the prior treatment requirement. 6) Have a performance status of 0 or 1 on the ECOG Performance Scale. 7) Have provided tissue for PD-L1 biomarker analysis from a newly obtained formalin-fixed tumor tissue from a recent biopsy of a tumor lesion not previously irradiated; no systemic antineoplastic therapy may be administered between the PD-L1 biopsy and initiating study medication. Although patients using tyrosine kinase inhibitors prior to treatment on this protocol may continue using these until it is time to begin the appropriate wash out period for these medications. For patients in whom obtaining a new tumor biopsy will be medically inappropriate, the investigator may appeal to the Sponsor’s study clinical director, and if there is agreement, the investigator may submit an archival formalin-fixed, paraffin-embedded tumor specimen for PD-L1 analysis. The tissue sample must be received and evaluated by the central vendor prior to randomization. Fine needle aspirates are not acceptable. Needle or excisional biopsies, or resected tissue is required. 8) Have a PD-L1 positive (either strongly or weakly) tumor as determined by IHC at a central laboratory. If a patient’s initial tumor specimen is not classified as PD-L1 positive by the central laboratory, a newly obtained specimen (different from the sample previously submitted) may be submitted for testing. If the newer specimen is classified as PD-L1 positive by the central laboratory, the patient meets this eligibility criterion. 9) Have resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less (except alopecia). If subject received major surgery or radiation therapy of > 30 Gy, they must have recovered from the toxicity and/or complications from the intervention. 10) Female subject of childbearing potential has a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test wi
Exclusion criteria
Exclusion criteria: 1) Has received prior therapy with docetaxel for NSCLC. 2) Is currently participating or has participated in a study of an investigational agent or using an investigational device within 30 days of the first dose of trial treatment. The 30 day window should be applied to the last dose of an antineoplastic investigational agent or last use of an investigational device with antineoplastic intent. 3) Is receiving systemic steroid therapy within three days prior to the first dose of trial treatment or receiving any other form of immunosuppressive medication (corticosteroid use on study for management of ECIs or as a pre-medication for docetaxel is allowed). 4) Is expected to require any other form of systemic or localized antineoplastic therapy while on trial (including maintenance therapy with another agent for NSCLC or radiation therapy). 5) Has received prior systemic cytotoxic chemotherapy, antineoplastic biological therapy (e.g., cetuximab), major surgery within 3 weeks of the first dose of trial treatment; received thoracic radiation therapy of > 30 Gy within 6 months of the first dose of trial treatment; received prior tyrosine kinase inhibitor therapy or completed palliative radiotherapy within 7 days of the first dose of trial treatment. 6) Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) or has participated in another MK-3475 clinical trial. 7) Has a known history of prior malignancy except if the patient has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy. 8) Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by MRI for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are using no steroids for at least three days prior to study medication. The two brain MRIs that were used to make the determination of stable disease must be submitted to the central imaging vendor, preferably while the subject is undergoing screening. These images should be submitted retrospectively for subjects that have already been randomized. 9) Has an active autoimmune disease, or a documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be exception to this rule. Subjects that require inhaled steroid or local steroid injections will not be excluded from the study. Subjects with hypothyroidism not from autoimmune disease and stable on hormone replacement will not be excluded from the study. 10) Has had an allogeneic tissue/solid organ transplant. 11) Has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management. Lymphangitic spread of the NSCLC is not exclusionary. 12) Has received or will receive a live vaccine within 30 days prior to the first administration of study medication. Seasonal flu vaccines that do not contain live virus are permitted. 13) Has an active in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1) To compare the overall survival (OS) of previously-treated subjects with NSCLC in the strongly positive PD-L1 stratum treated with MK-3475 compared to docetaxel. 2) To compare progression-free survival (PFS) per RECIST 1.1 by independent radiologists’ review of previously-treated subjects with NSCLC in the strongly positive PD-L1 stratum treated with MK-3475 compared to docetaxel. 3) To evaluate OS of previously-treated subjects with NSCLC whose tumors express PD-L1 and are treated with MK-3475 compared to docetaxel. 4) To evaluate PFS per RECIST 1.1 by independent radiologists’ review of previously-treated subjects with NSCLC whose tumors express PD-L1 and are treated with MK-3475 compared to docetaxel. 5)Objective: Evaluate safety and tolerability profile of MK-3475 in previously-treated subjects with NSCLC in the strongly positive PD-L1 stratum.;Secondary Objective: 1) To evaluate overall response rate (ORR) per RECIST 1.1 by independent radiologists’ review in previously-treated subjects with NSCLC in the strongly positive PD-L1 stratum and in overall study population whose tumors express PD-L1 treated with MK-3475 compared to docetaxel. 2) To evaluate response duration per RECIST 1.1 by independent radiologists’ review in previously-treated subjects with NSCLC in the strongly positive PD-L1 stratum and in overall study population treated with MK-3475 compared to docetaxel.;Primary end point(s): Overall Survival is the gold standard endpoint to demonstrate superiority of antineoplastic therapy. Progression free survival is an acceptable scientific endpoint for a randomized Phase III trial to demonstrate superiority of a new antineoplastic therapy, especially if it is believed that the median time to OS with the new therapy may be significantly longer than that seen with standard of care. RECIST 1.1 will be used to determine the dates of progression as this methodology is accepted by regulatory authorities. Because the treatment assignment i | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Importantly, PFS will also be assessed by irRC as determined by the investigators. ORR will be calculated by both methodologies, in addition to the duration of response. All main analyses will be performed in the strongly positive PD-L1 stratum. An analysis that includes all patients will be conducted for primary and secondary endpoints if the study is positive for that endpoint in the strongly positive PD-L1 stratum.;Timepoint(s) of evaluation of this end point: Biomarker testing will be occur during the course of the study. Evaluation of PFS and duration of response will be ongoing throughout the study. | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, Czech Republic, Denmark, France, Germany, Greece, Hungary, Italy, Japan, Korea, Republic of, Lithuania, Netherlands, Portugal, Russian Federation, South Africa, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Trials Operations
Merck Sharp & Dohme Limited
Outcome results
None listed