Clinical trial NCT01905657: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Non Small Cell Lung Cancer (NSCLC)
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2013-07-23
Enrollment: 1034
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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 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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
measure: Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
measure: Percentage of Participants Experiencing Adverse Events (AEs)
timeFrame: Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
measure: Percentage of Participants Discontinuing Study Drug Due to AEs
timeFrame: Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
Secondary outcomes:
measure: Overall Response Rate (ORR) by RECIST 1.1
timeFrame: Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
measure: Duration of Response (DOR) by RECIST 1.1
timeFrame: Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
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