Metastatic Non-squamous Non-small Cell Lung Cancer MedDRA version: 21.1 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Merck Sharp & Dohme LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have histologically or cytologically confirmed diagnosis of Stage IV (AJCC Version 8 or current version as applicable) non-squamous NSCLC 2. Have documentation of tumor activating EGFR mutation, specifically either DEL19 or L858R 3. Have investigator determined radiographic disease progression per RECIST 1.1 after treatment with an EGFR TKI therapy: a) Participants previously treated with 1st or 2nd generation EGFR TKI (eg, erlotinib/afatinib/gefitinib) are required to have confirmed documented absence of EGFR T790M mutation b) Participants with confirmed acquired T790M mutation after 1st or 2nd generation EGFR TKI (eg, erlotinib/afatinib/gefitinib) are required to have osimertinib TKI treatment failure prior to enrollment c) Participants previously failed osimertinib TKI treatment as 1st line therapy are eligible regardless of their EGFR T790M mutation status 4. Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions 5. Have provided archival tumor tissue sample or newly obtained (no anti-neoplastic therapy since biopsy) core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archival tissue 6. Be =18 years of age on the day of signing informed consent 7. Have a life expectancy of at least 3 months 8. Have an ECOG performance status of 0 or 1 within 7 days prior to the first dose of study treatment but before randomization 9. A male participant must agree to use contraception as detailed in protocol Section 10.3 during the treatment period and for at least 120 days after the last dose of pembrolizumab and up to 180 days after last dose of chemotherapeutic agents 10. A female participant is eligible to participate if she is not pregnant (see protocol Section 10.3), not breastfeeding, and at least one of the following conditions applies: a. Not a woman of childbearing potential (WOCBP) as defined in protocol Appendix 3 OR b. A WOCBP who agrees to follow the contraceptive guidance in protocol Section 10.3 during the treatment period and for at least 120 days after the last dose of pembrolizumab and up to 180 days after the last dose of chemotherapeutic agents 11. The participant provides written informed consent for the study 12. Have adequate organ function as defined in the protocol. Specimens must be collected within 10 days prior to the start of trial treatment Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 246 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 246
Exclusion criteria
Exclusion criteria: 1. Has predominantly squamous cell histology NSCLC. Mixed tumors will be categorized by the predominant cell type; if small cell elements are present, the participant is ineligible 2. Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible 3. A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization (see protocol Section 10.3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required 4. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137) 5. Has received prior systemic cytotoxic chemotherapy or investigational agent(s), excluding EGFR TKIs, for metastatic NSCLC 6. Has received prior radiotherapy within 2 weeks of start of study treatment or has received lugn radiation therapy of >30Gy within 6 months before the first dose of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-central nervous system (CNS) disease 7. Has received a live vaccine within 30 days prior to the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed 8. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment 9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment 10. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years 11. Has known active untreated CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, ie, without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment 12. Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients 13. Has a known sensitivity to any component of cisplatin, carboplatin, or pemetrexed 14. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed 15. Has a history of (non-infectious) pneumonitis that required steroids or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To compare PFS per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) based on blinded independent central review (BICR) of the combinations of pembrolizumab + chemotherapy versus saline placebo + chemotherapy - To compare overall survival (OS) of the combinations of pembrolizumab + chemotherapy versus saline placebo + chemotherapy ;Secondary Objective: - To compare objective response rate (ORR) per RECIST 1.1 based on BICR of the combinations of pembrolizumab + chemotherapy versus saline placebo + chemotherapy - To evaluate duration of response (DOR) of the combinations of pembrolizumab + chemotherapy versus saline placebo + chemotherapy - To evaluate the patient reported outcomes (PROs) mean score changes from baseline in global health status and quality of life scale between pembrolizumab + chemotherapy versus saline placebo + chemotherapy - To evaluate the PROs time to true deterioration (TTD) in the composite endpoint of cough, chest pain or dyspnea between pembrolizumab + chemotherapy versus saline placebo + chemotherapy - To evaluate the safety and tolerability of the combination of pembrolizumab + chemotherapy and saline placebo + chemotherapy ;Primary end point(s): 1) Progression-free Survival (PFS) per RECIST 1.1 assessed by BICR 2) Overall survival (OS);Timepoint(s) of evaluation of this end point: - 6 months after the last participant has been randomized (estimated ~30 months after the first participant randomized) - Final PFS analysis: 16 months after the last participant has been randomized AND approximately 414 PFS events have been observed (estimated ~40 months after the first participant randomized). - Final OS analysis: To be performed at 42 months after the last participant has been randomized AND at least ~approximately 423 deaths have occurred (estimated ~66 months after the first participant randomized). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Objective response rate (ORR) per RECIST 1.1 assessed by BICR;Timepoint(s) of evaluation of this end point: - 6 months after the last participant has been randomized (estimated ~30 months after the first participant randomized) - Final PFS analysis: 16 months after the last participant has been randomized AND approximately 414 PFS events have been observed (estimated ~40 months after the first participant randomized). - Final OS analysis: To be performed at 42 months after the last participant has been randomized AND at least ~approximately 423 deaths have occurred (estimated ~66 months after the first participant randomized). | — |
Countries
Australia, Brazil, Canada, China, France, Germany, Hong Kong, Israel, Italy, Japan, Korea, Republic of, Mexico, Spain, Sweden, Taiwan, United Kingdom, United States
Outcome results
None listed