Lung Cancer Clinical Trial
Study of Pemetrexed + Platinum Chemotherapy With or Without Pembrolizumab (MK-3475) in Adults With Tyrosine Kinase Inhibitor- (TKI)-Resistant Epidermal Growth Factor Receptor- (EGFR)-Mutated Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-789/KEYNOTE-789)
Summary
The purpose of this study is to evaluate the efficacy and safety of pemetrexed plus platinum chemotherapy (carboplatin or cisplatin) with or without pembrolizumab (MK-3475; KEYTRUDA®) in the treatment of adults with the following types of tyrosine kinase inhibitor (TKI)-resistant, epidermal growth factor receptor (EGFR)-mutated, metastatic non-squamous non-small cell lung cancer (NSCLC) tumors: 1) TKI-failures (including osimertinib [TAGRISSO®] failure) with T790M-negative mutation tumors, 2) T790M-positive mutation tumors with prior exposure to osimertinib, and 3) first-line osimertinib failure regardless of T790M mutation status.
The primary study hypotheses are that the combination of pembrolizumab plus chemotherapy has superior efficacy compared to saline placebo plus chemotherapy in terms of: 1) Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) based on blinded independent central review, and 2) Overall Survival (OS). This study will be considered to have met its success criteria if the combination of pembrolizumab plus chemotherapy is superior to saline placebo plus chemotherapy in terms of PFS or OS.
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed diagnosis of Stage IV non-squamous NSCLC.
Documentation of tumor activating EGFR mutation, specifically either DEL19 or L858R.
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 (e.g. 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 (e.g. 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. Note: TKI washout period for all participants is 1 week or 2 half-lives after last treatment dose, whichever is longer. TKI washout should be completed prior to first dose of study treatment.
Measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology.
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.
Life expectancy of at least 3 months.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of study treatment but before randomization.
Male participants must agree to use contraception 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.
Female participants must not be pregnant, not breastfeeding, and must agree to use contraception 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.
Adequate organ function.
Exclusion Criteria:
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.
Symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
Received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein-4 [CTLA-4], OX-40, CD137).
Received prior systemic cytotoxic chemotherapy or investigational agent(s), excluding EGFR TKIs, for metastatic NSCLC. [Notes: 1) Prior treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic NSCLC. 2) If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. 3) Prior exposure to traditional medicine(s) is allowed as long as therapy was discontinued at least 4 weeks prior to the first dose of study treatment.]
Received prior radiotherapy within 2 weeks of start of study treatment or has received lung radiation therapy of >30 Gray (Gy) 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.
Received a live vaccine within 30 days prior to the first dose of study treatment.
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.
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.
Known additional malignancy that is progressing or has required active treatment within the past 5 years. (Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.)
Known active untreated CNS metastases and/or carcinomatous meningitis.
Severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.
Known sensitivity to any component of cisplatin, carboplatin, or pemetrexed.
Active autoimmune disease that has required systemic treatment in past 2 years.
History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
Active infection requiring systemic therapy.
Known history of human immunodeficiency virus (HIV) infection.
Known history of Hepatitis B or known active Hepatitis C virus.
Known history of active tuberculosis (TB; Bacillus tuberculosis)
Pregnant, breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of pembrolizumab and up to 180 days after the last dose of chemotherapeutic agents.
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There are 151 Locations for this study
Los Angeles California, 90048, United States
Monterey California, 93940, United States
Orange California, 92868, United States
Santa Rosa California, 95403, United States
Evanston Illinois, 60201, United States
Sioux City Iowa, 51101, United States
Edina Minnesota, 55435, United States
Kansas City Missouri, 64111, United States
Albany New York, 12208, United States
Lake Success New York, 11042, United States
New York New York, 10022, United States
White Plains New York, 10601, United States
Portland Oregon, 97213, United States
Portland Oregon, 97227, United States
Dallas Texas, 75235, United States
Dallas Texas, 75390, United States
Salt Lake City Utah, 84106, United States
Charlottesville Virginia, 22903, United States
Milwaukee Wisconsin, 53226, United States
Camperdown New South Wales, 2050, Australia
Westmead New South Wales, 2145, Australia
Box Hill Victoria, 3128, Australia
Heidelberg Victoria, 3084, Australia
Natal Rio Grande Do Norte, 59075, Brazil
Ijui Rio Grande Do Sul, 98700, Brazil
Lajeado Rio Grande Do Sul, 95900, Brazil
Porto Alegre Rio Grande Do Sul, 90035, Brazil
Porto Alegre Rio Grande Do Sul, 90610, Brazil
Barretos Sao Paulo, 14784, Brazil
Ribeirao Preto Sao Paulo, 14048, Brazil
Sao Paulo , 01246, Brazil
Brampton Ontario, L6R 3, Canada
Toronto Ontario, M4N 3, Canada
Toronto Ontario, M5G 2, Canada
Montreal Quebec, H3T 1, Canada
Hefei Anhui, 23008, China
Beijing Beijing, 10002, China
Beijing Beijing, 10003, China
Beijing Beijing, 10003, China
Chongqing Chongqing, 40003, China
Fuzhou Fujian, 35001, China
Harbin Heilongjiang, 15008, China
Zhengzhou Henan, 45000, China
Changsha Hunan, 41000, China
Changsha Hunan, 41001, China
Nanjing Jiangsu, 21000, China
Chang chun Jilin, 13002, China
Changchun Jilin, 13010, China
Shanghai Shanghai, 20003, China
Shanghai Shanghai, 20043, China
XI An Shanxi, 71003, China
XI An Shanxi, 71006, China
Urumqi Xinjiang, 83000, China
Hangzhou Zhejiang, 31000, China
Hangzhou Zhejiang, 31001, China
Hangzhou Zhejiang, 31002, China
Lyon Auvergne, 69008, France
Caen Calvados, 14033, France
Dijon Cote-d'Or, 21000, France
Besancon Doubs, 25030, France
Antony Hauts-de-Seine, 92160, France
Tours Indre-et-Loire, 37044, France
Nancy Meurthe-et-Moselle, 54100, France
Le Mans Sarthe, 72000, France
Poitiers Vienne, 86021, France
Gerlingen Baden-Wurttemberg, 70839, Germany
Mannheim Baden-Wurttemberg, 68167, Germany
Wuerzburg Bayern, 97074, Germany
Oldenburg Niedersachsen, 26121, Germany
Duesseldorf Nordrhein-Westfalen, 40489, Germany
Essen Nordrhein-Westfalen, 45136, Germany
Muenster Nordrhein-Westfalen, 48149, Germany
Dresden Sachsen, 01307, Germany
Hamburg , 21075, Germany
Hong Kong , , Hong Kong
Hong Kong , , Hong Kong
Hong Kong , , Hong Kong
Kowloon , , Hong Kong
Tuen Mun , , Hong Kong
Ashkelon HaDarom, 78306, Israel
Beer-Sheva HaDarom, 84571, Israel
Kfar-Saba HaMerkaz, 44281, Israel
Petah Tikva HaMerkaz, 49414, Israel
Afula HaTsafon, 18341, Israel
Haifa Heifa, 31096, Israel
Ramat Gan Tell Abib, 52656, Israel
Tel Aviv Tell Abib, 64239, Israel
Milano Lombardia, 20141, Italy
Taormina Messina, 98039, Italy
Orbassano Torino, 10043, Italy
Bari , 70124, Italy
Firenze , 50134, Italy
Napoli , 80131, Italy
Roma , 00128, Italy
Nagoya Aichi, 460-0, Japan
Nagoya Aichi, 464-8, Japan
Toyoake Aichi, 470-1, Japan
Kashiwa Chiba, 277-8, Japan
Matsuyama Ehime, 791-0, Japan
Akashi Hyogo, 673-8, Japan
Kanazawa Ishikawa, 920-8, Japan
Yokohama Kanagawa, 241-8, Japan
Hirakata Osaka, 573-1, Japan
Sunto-gun Shizuoka, 411-8, Japan
Fukuoka , 810-8, Japan
Fukuoka , 812-8, Japan
Niigata , 951-8, Japan
Okayama , 700-8, Japan
Osaka , 541-8, Japan
Tokyo , 104-0, Japan
Tokyo , 105-8, Japan
Tokyo , 113-8, Japan
Wakayama , 641-8, Japan
Cheongju si Chungcheongbuk-do [Chungbuk], 28644, Korea, Republic of
Incheon Incheon-gwangyeoksi [Incheon], 21565, Korea, Republic of
Gyeonggi-do Kyonggi-do, 10408, Korea, Republic of
Seongnam-si Kyonggi-do, 13620, Korea, Republic of
Seoul Seoul-teukbyeolsi [Seoul], 03080, Korea, Republic of
Seoul Seoul-teukbyeolsi [Seoul], 05505, Korea, Republic of
Seoul Seoul-teukbyeolsi [Seoul], 06351, Korea, Republic of
Seoul Seoul-teukbyeolsi [Seoul], 06591, Korea, Republic of
Ulsan Ulsan-Kwangyokshi, 44033, Korea, Republic of
Guadalajara Jalisco, 44280, Mexico
Mexico City , 14050, Mexico
Oaxaca , 68000, Mexico
Tlalpan , 14080, Mexico
Badalona Barcelona [Barcelona], 08916, Spain
Barcelona Barcelona [Barcelona], 08025, Spain
Barcelona Barcelona [Barcelona], 08035, Spain
Madrid , 28034, Spain
Madrid , 28041, Spain
Malaga , 29010, Spain
Sevilla , 41009, Spain
Linkoping Ostergotlands Lan [se-05], 581 8, Sweden
Lund Skane Lan [se-12], 221 8, Sweden
Solna Stockholms Lan [se-01], 171 6, Sweden
Goteborg Vastra Gotalands Lan [se-14], 413 4, Sweden
New Taipei City New Taipei, 231, Taiwan
Changhua , 50006, Taiwan
Hsinchu , 300, Taiwan
Hualien , 970, Taiwan
Kaohsiung , 833, Taiwan
New Taipei , 235, Taiwan
Taichung , 40447, Taiwan
Taichung , 40705, Taiwan
Tainan , 704, Taiwan
Taipei , 100, Taiwan
Taipei , 104, Taiwan
Taipei , 11217, Taiwan
Taoyuan , 333, Taiwan
Brighton Brighton And Hove, BN2 5, United Kingdom
Edinburgh Edinburgh, City Of, EH4 2, United Kingdom
Leicester Leicestershire, LE1 5, United Kingdom
London London, City Of, NW1 2, United Kingdom
London London, City Of, SW10 , United Kingdom
Birmingham , B9 5S, United Kingdom
Leeds , LS9 7, United Kingdom
Romford , RM7 0, United Kingdom
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