Phase III study of Pemetrexed+Platinum with or without Pembrolizumab in first line (1L) metastatic non-squamous NSCLC.
- Conditions
- non-squamous non-small cell lung cancerTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-003694-15-GB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 570
•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/neoadjuvant chemotherapy will be permitted if recent biopsy is not feasible.
•Be =18 years of age 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 (Section 5.7.2), 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.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
•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.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
•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.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 302
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 268
•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) for metastatic disease
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, peritoneal 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 IDO, PD-L1, IL-2R, GITR
•Has an active infection requiring therapy
•Has known history of Human Immunodeficiency Virus (HIV) (known HIV 1/2 antibodies positive)
•Has known active Hepatit
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method