A Randomized, Double-Blind, Phase III Study of Platinum+Pemetrexed Chemotherapy with or without Pembrolizumab (MK-3475) in First Line Metastatic Non-squamous Non-small Cell Lung Cancer Subjects (KEYNOTE-189).
- Conditions
- lung cancer10038666
- Registration Number
- NL-OMON50379
- Lead Sponsor
- Merck Sharp & Dohme (MSD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 9
•Have a histologically-confirmed or cytologically-confirmed diagnosis of stage
IV (M1a or M1b AJCC 7th edition) nonsquamous NSCLC., • Have confirmation that
EGFR or ALK-directed therapy is not indicated., •Have measurable disease based
on RECIST 1.1 as determined by the local site investigator/radiology
assessment. Target lesions situated in a previously irradiated
area are considered measurable if progression has been demonstrated in such
lesions.
•Have not received prior systemic treatment for their advanced/metastatic
NSCLC. Subjects who received adjuvant or neoadjuvant therapy are eligible if
the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the
development of metastatic disease., •Have provided tumor tissue from locations
not radiated prior to biopsy; formalin-fixed specimens after the subject has
been diagnosed with metastatic disease will be preferred for determination of
PD-L1 status prior to randomization. Biopsies obtained prior to receipt of
adjuvant chemotherapy will be permitted if recent biopsy is not feasible., •Be
18 years of age or older on day of signing informed consent. , • Have a life
expectancy of at least 3 months., •Have a ECOG performance status of 0 or 1,
•Have adequate organ function as indicated by the laboratory values specified
in the protocol , •If female of childbearing potential, have a negative urine
or serum pregnancy test within 72 hours prior to receiving the first dose of
study medication. If the urine test is positive or cannot be confirmed as
negative, a serum pregnancy test will be required., •If female of childbearing
potential, be willing to use an adequate method of contraception as outlined in
the protocol, for the course of the study through 120 days after the last dose
of study medication or through 180 days after last dose of chemotherapeutic
agents as specified in the protocol. , •If male subject with a female
partner(s) of child-bearing potential, must agree to use an adequate method of
contraception as outlined in the protocol, starting with the first dose of
study therapy through 120 days after the last dose of study therapy or through
180 days after last dose of chemotherapeutic agents as specified in the
protocol. Males with pregnant partners must agree to use a condom; no
additional method of contraception is required for the pregnant partner.,
•Subject has voluntarily agreed to participate by giving written informed
consent/assent for the trial. The subject may also provide consent/assent for
Future Biomedical Research. However, the subject may participate in the main
trial without participating in Future Biomedical Research.
•Has predominantly squamous cell histology NSCLC. Mixed tumors will be
categorized by the predominant cell type; if small cell elements are present,
the subject is ineligible., •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 trial treatment:
a)Has received prior systemic cytotoxic chemotherapy for metastatic disease
b)Has received antineoplastic biological therapy (e.g., erlotinib, crizotinib,
cetuximab)
c)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
trial treatment, •Completed palliative radiotherapy within 7 days of the first
dose of trial treatment, •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. Seasonal flu vaccines that do not
contain live virus are permitted., •Has clinically active diverticulitis,
intra-abdominal abscess, GI obstruction, abdominal carcinomatosis, •Has a known
history of prior malignancy except if the patient 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. Subjects with previously treated
brain metastases may participate provided they are clinically stable for at
least 2 weeks and, have no evidence of new or enlarging brain metastases and
also are off steroids 3 days prior to dosing with study medication. Stable
brain metastases by this definition should be established prior to the first
dose of study medication. Subjects with known untreated asymptomatic brain
metastases may participate but will require regular imaging of the brain as a
site of disease., •Previously had a severe hypersensitivity reaction to
treatment with another mAb., •Has a known sensitivity to any component of
cisplatin, carboplatin or pemetrexed, •Has active autoimmune disease that has
required systemic treatment in past 2 years (i.e. with use of disease modifying
agents, corticosteroids or immunosuppressive drugs). Replacement therapy
(e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy
for adrenal or pituitary insufficiency, etc.) is not considered a form of
systemic treatment., •Is on chronic systemic steroids. Subjects with asthma
that require intermittent use of bronchodilators, inhaled steroids, or local
steroid injections would not be excluded from the study., •Is unable to
interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), other
than an aspirin dose <= 1.3 g per day, for a 5-day period (8-day period for
long-acting agents, such as piroxicam)., •Is unable or unwilling to take folic
acid or vitamin B12 supplementation., •Had prior treatment with any other
anti-PD-1, or PD-L1 or PD-L2 agent or an antibody targeting other
immuno-regulatory receptors or mechanisms. Has participated in any other
MK-3475 trial and has been treated with MK-3475., Examples of such antibodies
include (but are not limited to) antibodies against ID
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint of the trial is PFS per RECIST 1.1 by central imaging<br /><br>vendor review.<br /><br>Overal Survival, defined as time from randomization to death due to any cause. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Objective Response Rate (ORR) - RECIST 1.1 assessed by BICR<br /><br>Duration of Response (DOR) - RECIST 1.1 assessed by BICR</p><br>