Overview

This trial is active, not recruiting.

Condition non-small cell lung carcinoma
Treatments pembrolizumab, paclitaxel, carboplatin, pemetrexed, cisplatin, gemcitabine
Phase phase 3
Target PD-1
Sponsor Merck Sharp & Dohme Corp.
Start date August 2014
End date May 2016
Trial size 305 participants
Trial identifier NCT02142738, 142728, 2014-000323-25, 3475-024

Summary

This is an efficacy and safety study to assess pembrolizumab (MK-3475/SCH 900475) compared to standard of care (SOC) platinum-based chemotherapies in the treatment of participants with previously untreated stage IV, programmed cell death ligand 1 (PD-L1) strong expressing Non-Small Cell Lung Cancer (NSCLC). The primary hypothesis of this study is that participants with PD-L1 strong NSCLC will have a longer Progression Free Survival (PFS), as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) when treated with pembrolizumab than when treated with platinum-based chemotherapies.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants receive pembrolizumab 200 mg, administered as intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles or until documented PD.
pembrolizumab MK-3475
Pembrolizumab IV solution
(Active Comparator)
Participants receive Paclitaxel 200 mg/m^2 and Carboplatin Area Under the Curve (AUC) 5 or 6, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional pemetrexed 500 mg/m^2 every three weeks (Q3W) maintenance for the remainder of the study or until documented PD. If PD occurs, participants may be able to receive pembrolizumab Q3W for the remainder of the study or until documented PD.
paclitaxel
Paclitaxel IV solution
carboplatin
Carboplatin IV solution
pemetrexed
Pemetrexed IV solution
(Active Comparator)
Participants receive pemetrexed 500 mg/m^2 and carboplatin AUC 5 or 6, IV infusion on Day 1 of each 21-day cycle for 4-6 cycles; participants with non-squamous histologies may then receive pemetrexed 500 mg/m^2 on Day 1 of each 21-day cycle as maintenance therapy for the remainder of the study or until documented PD. If PD occurs, participants may be able to receive pembrolizumab Q3W for the remainder of the study or until documented PD.
carboplatin
Carboplatin IV solution
pemetrexed
Pemetrexed IV solution
(Active Comparator)
Participants receive Pemetrexed 500 mg/m^2 and Cisplatin 75 mg/m^2, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional pemetrexed 500 mg/m^2 Q3W maintenance for the remainder of the study or until documented PD. If PD occurs, participants may be able to receive pembrolizumab Q3W for the remainder of the study or until documented PD.
pemetrexed
Pemetrexed IV solution
cisplatin
Cisplatin IV solution
(Active Comparator)
Participants receive Gemcitabine 1250 mg/m^2, administered as IV infusion on Days 1 and 8 of each 21-day cycle and Carboplatin AUC 5 or 6, administered as IV infusion on Day 1 of a 21-day cycle, for 4-6 cycles or until documented PD. If PD occurs, participants may be able to receive pembrolizumab Q3W for the remainder of the study or until documented PD.
carboplatin
Carboplatin IV solution
gemcitabine
Gemcitabine IV solution
(Active Comparator)
Participants receive Gemcitabine 1250 mg/m^2, administered as IV infusion on Days 1 and 8 of each 21-day cycle and Cisplatin 75 mg/m^2, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles or until documented PD. If PD occurs, participants may be able to receive pembrolizumab Q3W for the remainder of the study or until documented PD.
cisplatin
Cisplatin IV solution
gemcitabine
Gemcitabine IV solution

Primary Outcomes

Measure
Progression Free Survival (PFS)
time frame: Up to 2 years

Secondary Outcomes

Measure
Overall Survival (OS)
time frame: Up to 2 years
Objective Response Rate (ORR)
time frame: Up to 2 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Histological or cytological diagnosis of Stage IV NSCLC lacking epidermal growth factor receptor (EGFR)-sensitizing mutation and/or anaplastic lymphoma kinase (ALK) translocation, and received no prior systemic chemotherapy treatment for their metastatic NSCLC - At least one radiographically measurable lesion per RECIST 1.1 - Life expectancy of at least 3 months - Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status - Adequate organ function - No history of prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cervical cancer, or has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy - Provided newly obtained formalin fixed tumor tissue from a biopsy of a tumor AFTER the diagnosis of metastatic disease has been made AND from a site not previously irradiated - PD-L1 strong expressing tumor as determined by immunohistochemistry (IHC) at a central laboratory - Female participants must have a negative pregnancy test at screening if of childbearing potential or be of non-childbearing potential - Female participants of childbearing potential and male partners with female partners of childbearing potential must agree to use 2 adequate barrier methods of contraception during the study and for 120 days after last dose of study drug and up to 180 days after last dose of chemotherapy Exclusion Criteria: - EGFR sensitizing mutation and/or ALK translocation - Currently participating or has participated in a study of an investigational agent or using an investigational device within 30 days of first dose of study drug - Tumor specimen is not evaluable for PD-L1 expression by the central laboratory - Receiving systemic steroid therapy <= 3 days prior to first dose of study drug or receiving any other form of immunosuppressive medication - Expected to require any other form of systemic or localized antineoplastic therapy during the study - Received prior systemic cytotoxic chemotherapy, biological therapy, major surgery within 3 weeks of first dose of study drug; received thoracic radiation therapy of > 30 gray (Gy) within 6 months of first dose of study drug - Received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor [TNFR] family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) - Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis - Active autoimmune disease that has required systemic treatment in past 2 years - Allogenic tissue/solid organ transplant - Interstitial lung disease or pneumonitis that has required oral or IV steroids - Received or will receive a live vaccine within 30 days prior to first dose of study drug - Active infection requiring IV systemic therapy - Known history of human immunodeficiency virus (HIV) - Known active tuberculosis, or hepatitis B or C - Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study - Pregnant or breastfeeding, or expecting to conceive or father children during the study and through 120 days after last dose of study drug - Immediate family member who is investigational site or sponsor staff directly involved with this study

Additional Information

Official title A Randomized Open-Label Phase III Trial of MK-3475 Versus Platinum Based Chemotherapy in 1L Subjects With PD-L1 Strong Metastatic Non-Small Cell Lung Cancer
Description Treatment Phase: Participants randomized to pembrolizumab will be treated for up to 35 cycles or until documented progressive disease (PD) occurs. Participants randomized to SOC chemotherapies will be treated with their randomized study drug for up to 4-6 cycles. After this, participants with non-squamous histologies may choose to be treated with maintenance pemetrexed for the remainder of the study or until PD occurs. Participants randomized to receive SOC chemotherapy may be eligible to receive pembrolizumab if crossover criteria are met. Cross-Over Phase: This is only applicable for participants randomized to receive SOC. Participants will be treated with pembrolizumab for the remainder of the study or until PD occurs.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Merck Sharp & Dohme Corp..