Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01905657




Registration number
NCT01905657
Ethics application status
Date submitted
18/07/2013
Date registered
23/07/2013
Date last updated
6/10/2021

Titles & IDs
Public title
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)
Scientific 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
Secondary ID [1] 0 0
2012-004391-19
Secondary ID [2] 0 0
3475-010
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non Small Cell Lung Cancer (NSCLC) 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Pembrolizumab
Treatment: Drugs - Docetaxel

Experimental: Pembrolizumab 2 mg/kg - Participants received pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes Q3W for up to 2 years.

Experimental: Pembrolizumab 10 mg/kg - Participants received pembrolizumab 10 mg/kg IV over 30 minutes Q3W for up to 2 years.

Active comparator: Docetaxel 75 mg/m^2 - Participants received docetaxel 75 mg/m\^2 IV over 1 hour Q3W for up to 2 years.


Treatment: Other: Pembrolizumab
IV infusion

Treatment: Drugs: Docetaxel
IV infusion
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
Primary outcome [2] 0 0
Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [2] 0 0
Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
Primary outcome [3] 0 0
Percentage of Participants Experiencing Adverse Events (AEs)
Timepoint [3] 0 0
Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
Primary outcome [4] 0 0
Percentage of Participants Discontinuing Study Drug Due to AEs
Timepoint [4] 0 0
Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
Secondary outcome [1] 0 0
Overall Response Rate (ORR) by RECIST 1.1
Timepoint [1] 0 0
Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
Secondary outcome [2] 0 0
Duration of Response (DOR) by RECIST 1.1
Timepoint [2] 0 0
Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/08/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/09/2020
Sample size
Target
Accrual to date
Final
1034
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
China
State/province [1] 0 0
Beijing

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01905657
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01905657