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

Not Recruiting

Trial ID: NCT01905657


This study compared two doses of pembrolizumab (MK-3475) versus docetaxel in participants with non-small cell lung cancer (NSCLC) who had experienced disease progression after platinum-containing systemic therapy. Participants were assigned randomly to receive either pembrolizumab 2 mg/kg once every three weeks (Q3W), pembrolizumab 10 mg/kg Q3W or docetaxel 75 mg/m^2 Q3W. The total number of participants randomized depended upon demonstration of sufficient objective responses at an interim analysis. Eligible participants who were allocated to the first course of pembrolizumab (2 mg/kg Q3W or 10 mg/kg Q3W) and experienced disease progression, to be permitted to receive a second course of pembrolizumab as long as Inclusion/Exclusion criteria were met. Protocol Amendment 12 (effective date: 09 Dec 2015) enabled eligible participants who were allocated to docetaxel and experienced disease progression, to be permitted to switch over to receive pembrolizumab 2 mg/kg Q3W as long as Inclusion/Exclusion criteria were met. With Protocol Amendment 15 (effective date: 03 Jan 2018), all second course and switch over participants will receive pembrolizumab 200 mg Q3W. Response or progression during the second and switch over pembrolizumab courses will not count towards efficacy outcome measures, and adverse events during the second and switch over pembrolizumab courses will not count towards safety outcome measures. Also with Amendment 15, once a participant has achieved the study objective or the study has ended, the participant will be discontinued from this study and enrolled in an extension study (Keynote 587; NCT03486873) to continue protocol-defined assessments and treatment. Switch over participants who have not transitioned to pembrolizumab will be considered for the extension study on a case-by-case basis. The primary study hypotheses are that pembolizumab prolongs Overall Survival (OS) and Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by independent radiologists' review in previously-treated participants with NSCLC in the strongly positive programmed cell death ligand 1 (PD-L1) stratum compared to docetaxel and in participants whose tumors express PD-L1 compared to docetaxel.

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

Stanford Investigator(s)

Joel Neal, MD, PhD
Joel Neal, MD, PhD

Associate Professor of Medicine (Oncology)


Inclusion Criteria:

   - Life expectancy of at least 3 months

   - Histologically- or cytologically-confirmed diagnosis of NSCLC that is anti-programmed
   cell death ligand 1 (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 3 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 Gy 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

   - Known history or active human immunodeficiency virus (HIV), hepatitis B, or hepatitis

   - 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


drug: Docetaxel

biological: pembrolizumab

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

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