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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02775435




Registration number
NCT02775435
Ethics application status
Date submitted
15/05/2016
Date registered
17/05/2016
Date last updated
6/10/2023

Titles & IDs
Public title
A Study of Carboplatin-Paclitaxel/Nab-Paclitaxel Chemotherapy With or Without Pembrolizumab (MK-3475) in Adults With First Line Metastatic Squamous Non-small Cell Lung Cancer (MK-3475-407/KEYNOTE-407)
Scientific title
A Randomized, Double-Blind, Phase III Study of Carboplatin-Paclitaxel/Nab-Paclitaxel Chemotherapy With or Without Pembrolizumab (MK-3475) in First Line Metastatic Squamous Non-small Cell Lung Cancer Subjects (KEYNOTE-407)
Secondary ID [1] 0 0
173568
Secondary ID [2] 0 0
3475-407
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Pembrolizumab
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Nab-paclitaxel
Treatment: Drugs - Carboplatin
Treatment: Drugs - Saline placebo for pembrolizumab

Experimental: Pembrolizumab + Chemotherapy - Participants receive pembrolizumab 200 mg by intravenous (IV) infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.

Active Comparator: Chemotherapy - Participants receive normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.


Other interventions: Pembrolizumab
IV infusion

Treatment: Drugs: Paclitaxel
IV infusion

Treatment: Drugs: Nab-paclitaxel
IV infusion

Treatment: Drugs: Carboplatin
IV infusion Carboplatin dose should not to exceed 900 mg.

Treatment: Drugs: Saline placebo for pembrolizumab
IV infusion
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [1] 0 0
Up to approximately 19 months (Database cutoff date of 03-Apr-2018)
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to approximately 19 months (Database cutoff date of 03-Apr-2018)
Secondary outcome [1] 0 0
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [1] 0 0
Up to approximately 19 months (Database cutoff date of 03-Apr-2018)
Secondary outcome [2] 0 0
Duration of Response (DOR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [2] 0 0
Up to approximately 19 months (Database cutoff date of 03-Apr-2018)
Secondary outcome [3] 0 0
Number of Participants Who Experienced an Adverse Event (AE)
Timepoint [3] 0 0
Up to approximately 19 months (Database cutoff date of 03-Apr-2018)
Secondary outcome [4] 0 0
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Timepoint [4] 0 0
Up to approximately 19 months (Database cutoff date of 03-Apr-2018)

Eligibility
Key inclusion criteria
- Has a histologically or cytologically confirmed diagnosis of stage IV (M1a or
M1b-American Joint Committee on Cancer [AJCC] 7th edition) squamous NSCLC.

- Has measurable disease based on RECIST 1.1 as determined by the local site
investigator/radiology assessment.

- Has not received prior systemic treatment for metastatic NSCLC.

- Has provided tumor tissue from locations not radiated prior to biopsy.

- Has a life expectancy of at least 3 months.

- Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
Performance Status.

- Has adequate organ function.

- If female of childbearing potential, is willing to use an adequate method of
contraception for the course of the study through 180 days after the last dose of
study drug.

- If male with a female partner(s) of child-bearing potential, must agree to use an
adequate method of contraception starting with the first dose of study drug through 95
days after the last dose of study drug. Males with pregnant partners must agree to use
a condom; no additional method of contraception is required for the pregnant partner.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Has non-squamous histology NSCLC.

- Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks prior to administration of pembrolizumab.

- Before the first dose of study drug: a) Has received prior systemic cytotoxic
chemotherapy for metastatic disease; b) Has received other targeted or biological
antineoplastic therapy (e.g., erlotinib, crizotinib, cetuximab) for metastatic
disease; c) Has had major surgery (<3 weeks prior to first dose).

- Received radiation therapy to the lung that is > 30 Gy within 6 months of the first
dose of study drug.

- Completed palliative radiotherapy within 7 days of the first dose of study drug.

- Is expected to require any other form of antineoplastic therapy while on study.

- Has received a live-virus vaccination within 30 days of planned treatment start.

- Has a known history of prior malignancy except if the participant has undergone
potentially curative therapy with no evidence of that disease recurrence for 5 years
since initiation of that therapy.

- Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis.

- Has pre-existing peripheral neuropathy that is = Grade 2 by Common Terminology
Criteria for Adverse Events (CTCAE) version 4 criteria.

- Previously had a severe hypersensitivity reaction to treatment with another monoclonal
antibody.

- Has a known sensitivity to any component of carboplatin or paclitaxel or
nab-paclitaxel.

- Has active autoimmune disease that has required systemic treatment in past 2 years.

- Is on chronic systemic steroids.

- Had prior treatment with any other anti-programmed cell death 1 (anti-PD-1), or
programmed cell death ligand 1 (PD-L1) or PD-L2 agent or an antibody or a small
molecule targeting other immuno-regulatory receptors or mechanisms.

- Has participated in any other pembrolizumab trial and has been treated with
pembrolizumab.

- Has an active infection requiring therapy.

- Has known history of Human Immunodeficiency Virus (HIV).

- Has known active Hepatitis B or C. Active Hepatitis B.

- Is, at the time of providing documented informed consent, a regular user (including
"recreational use") of any illicit drugs or has a recent history (within the last
year) of substance abuse (including alcohol).

- Has interstitial lung disease or a history of pneumonitis that required oral or
intravenous glucocorticoids to assist with management.

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
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
9/06/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
14/09/2023
Sample size
Target
Accrual to date
Final
559
Recruitment in Australia
Recruitment state(s)

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a study of carboplatin and paclitaxel or nano particle albumin-bound paclitaxel
(nab-paclitaxel) with or without pembrolizumab (MK-3475, KEYTRUDA®) in adults with first line
metastatic squamous non-small cell lung cancer (NSCLC).

The primary hypotheses are that treatment with pembrolizumab prolongs: 1) Progression-free
Survival (PFS) by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as
assessed by a blinded central imaging vendor compared to placebo, and 2) Overall Survival
(OS).

After analysis of interim results was conducted, the protocol was amended (Amendment 5) to
allow participants the option to discontinue placebo in the control arm and to switch to
pembrolizumab in the event of documented progressive disease as assessed by central review.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02775435
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/ct2/show/NCT02775435