Study of Two Doses of MK-3475 (Pembrolizumab) Versus Docetaxel in Previously-Treated Participants With Non-Small Cell Lung Cancer (MK-3475-010/KEYNOTE-010)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01905657
First received: July 18, 2013
Last updated: April 7, 2016
Last verified: April 2016
  Purpose

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.


Condition Intervention Phase
Non Small Cell Lung Cancer (NSCLC)
Biological: pembrolizumab
Drug: docetaxel
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Progression free survival (PFS) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Number of participants experiencing adverse events [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
  • Number of participants discontinuing study drug due to adverse events [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall response rate (ORR) by RECIST 1.1 [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Response duration by RECIST 1.1 [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Enrollment: 1034
Study Start Date: August 2013
Estimated Study Completion Date: March 2019
Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pembrolizumab Low Dose
Participants receive pembrolizumab, intravenously (IV) over 30 minutes Q3W.
Biological: pembrolizumab
Participants who experience disease progression on docetaxel may be eligible to crossover to receive pembrolizumab.
Experimental: Pembrolizumab High Dose
Participants receive pembrolizumab, IV over 30 minutes Q3W.
Biological: pembrolizumab
Participants who experience disease progression on docetaxel may be eligible to crossover to receive pembrolizumab.
Active Comparator: Docetaxel 75 mg/m^2
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.
Biological: pembrolizumab
Participants who experience disease progression on docetaxel may be eligible to crossover to receive pembrolizumab.
Drug: docetaxel
Participants who initially receive docetaxel may be eligible to crossover to receive pembrolizumab.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01905657

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01905657     History of Changes
Other Study ID Numbers: 3475-010  2012-004391-19  132355 
Study First Received: July 18, 2013
Last Updated: April 7, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Docetaxel
Pembrolizumab
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2016