Overview

This trial is active, not recruiting.

Condition non small cell lung cancer (nsclc)
Treatments pembrolizumab, docetaxel
Phase phase 2/phase 3
Target PD-1
Sponsor Merck Sharp & Dohme Corp.
Start date August 2013
End date September 2015
Trial size 1034 participants
Trial identifier NCT01905657, 132355, 2012-004391-19, 3475-010

Summary

This study will compare two doses of pembrolizumab versus docetaxel in participants with non-small cell lung cancer (NSCLC) who have experienced disease progression after platinum-containing systemic therapy. Participants will be assigned randomly to receive either Low Dose or High Dose pembrolizumab every three weeks (Q3W), or docetaxel at 75 mg/m^2 Q3W. This study will use an adaptive trial design so that the total number of participants randomized will depend upon demonstration of sufficient objective responses at interim analysis. If the pembrolizumab Low Dose arm is closed, participants may receive pembrolizumab High Dose therapy.

Based on the positive outcome of the Overall Survival (OS) analysis, Protocol Amendment 12 enables eligible participants who were allocated to docetaxel and experienced disease progression, to be permitted to crossover to receive MK-3475 Low Dose Q3W as long as Inclusion/Exclusion criteria are met. These participants will be participating in the Cross-Over Phase.

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, intravenously (IV) over 30 minutes Q3W.
pembrolizumab
Participants who experience disease progression on docetaxel may be eligible to crossover to receive pembrolizumab.
(Experimental)
Participants receive pembrolizumab, IV over 30 minutes Q3W.
pembrolizumab
Participants who experience disease progression on docetaxel may be eligible to crossover to receive pembrolizumab.
(Active Comparator)
Participants receive 75 mg/m^2 docetaxel, IV over 1 hour Q3W. Participants who experience disease progression, may be eligible to crossover to receive Pembrolizumab Low Dose Q3W.
pembrolizumab
Participants who experience disease progression on docetaxel may be eligible to crossover to receive pembrolizumab.
docetaxel
Participants who initially receive docetaxel may be eligible to crossover to receive pembrolizumab.

Primary Outcomes

Measure
Overall Survival (OS)
time frame: Up to 3 years
Progression free survival (PFS) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
time frame: Up to 3 years
Number of participants experiencing adverse events
time frame: Up to 3 years
Number of participants discontinuing study drug due to adverse events
time frame: Up to 3 years

Secondary Outcomes

Measure
Overall response rate (ORR) by RECIST 1.1
time frame: Up to 3 years
Response duration by RECIST 1.1
time frame: Up to 3 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Life expectancy of at least 3 months - Histologically- or cytologically-confirmed diagnosis of non-small cell lung cancer (NSCLC) that is PD-L1 positive per central laboratory review - At least one bi-dimensional measurable lesion - Radiographic progression after treatment with at least 2 cycles of a platinum-containing doublet - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Exclusion Criteria: - Prior therapy with docetaxel for NSCLC - Receiving systemic steroid therapy within three days prior to the first dose of study treatment or receiving any other form of immunosuppressive medication - Currently participating or has participated in a study using an investigational antineoplastic agent or device within 30 days of first dose - Expected to require any other form of systemic or localized antineoplastic therapy while on trial - History of allogeneic tissue/solid organ transplant - Prior systemic cytotoxic chemotherapy, antineoplastic biological therapy (e.g., cetuximab), major surgery within 3 weeks of the first dose of study drug; received thoracic radiation therapy of >30 Gray within 6 months of the first dose of study drug; received prior tyrosine kinase inhibitor therapy or completed palliative radiotherapy within 7 days of the first dose of study drug - Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2, anti-tumor necrosis factor 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 took part in another pembrolizumab trial - Known 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, and has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy - Known active central nervous system (CNS) metastases and/or carcinomatous meningitis - Active autoimmune disease, or a documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents - Interstitial lung disease, or history of pneumonitis requiring systemic steroids for treatment - Known history or active human immunodeficiency virus (HIV), hepatitis B, or hepatitis C - Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial through 120 days after last dose of pembrolizumab or 180 days after last dose of docetaxel

Additional Information

Official title A Phase II/III Randomized Trial of Two Doses of MK-3475 (SCH900475) Versus Docetaxel in Previously Treated Subjects With Non-Small Cell Lung Cancer
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by Merck Sharp & Dohme Corp..
Location data was received from the National Cancer Institute and was last updated in April 2016.