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)
Non-small Cell Lung Cancer

About this trial
This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring PD1, PD-1, PDL1, PD-L1
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.
Sites / Locations
- Cedars-Sinai Medical Center ( Site 0070)
- Pacific Cancer Care ( Site 0058)
- UC Irvine Medical Center/Chao Family Comprehensive Cancer Center ( Site 0092)
- St. Joseph Heritage Healthcare ( Site 0003)
- North Shore University Health System ( Site 0030)
- Siouxland Regioinal Cancer Center dba June E. Nylen Cancer Center ( Site 0065)
- Southdale Cancer Care, University of Minnesota Medical Center- Edina ( Site 0048)
- Saint Lukes Hospital of Kansas City ( Site 0060)
- New York Oncology Hematology P.C ( Site 8000)
- Monter Cancer Center ( Site 0054)
- Memorial Sloan Kettering Cancer Center-Rockerfeller Patient Pavilion ( Site 0049)
- White Plains Hospital Center for Cancer Care ( Site 0014)
- Providence Portland Medical Center ( Site 0097)
- Kaiser Permanente Northwest ( Site 0037)
- Parkland Health & Hospital System ( Site 2102)
- University of Texas Southwestern Medical Center at Dallas ( Site 0035)
- Utah Cancer Specialists ( Site 0001)
- Emily Couric Clinical Cancer Center ( Site 0020)
- Froedtert Hospital & the Medical College of Wisconsin ( Site 0041)
- Chris OBrien Lifehouse ( Site 0200)
- Westmead Hospital ( Site 0201)
- Eastern Health ( Site 0202)
- Austin Health ( Site 0203)
- Liga Norte Riograndense Contra o Cancer ( Site 1909)
- Hospital de Caridade de Ijui ( Site 1907)
- Hospital Bruno Born ( Site 1913)
- Hospital de Clinicas de Porto Alegre ( Site 1905)
- Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 1904)
- Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 1911)
- Hosp. Clinicas da Fac. de Medicina de Ribeirao Preto - USP ( Site 1912)
- Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 1903)
- William Osler Health System ( Site 0100)
- Sunnybrook Health Sciences, Odette Cancer Centre ( Site 0102)
- Princess Margaret Cancer Centre ( Site 0104)
- Jewish General Hospital ( Site 0105)
- The First Affiliated Hospital of Anhui Medical University ( Site 0721)
- Cancer Hospital Chinese Academy of Medical Sciences ( Site 0717)
- Peking Union Medical College Hospital ( Site 0703)
- Beijing Cancer Hospital ( Site 0718)
- Southwest Hospital, The Third Military Medical University ( Site 0725)
- Fujian Cancer Hospital ( Site 0723)
- The Affiliated Tumour Hospital of Harbin Medical University ( Site 0706)
- Henan Cancer Hospital ( Site 0711)
- Xiangya Hospital of Central South University ( Site 0710)
- Hunan Cancer Hospital ( Site 0722)
- Jiangsu Cancer Hospital ( Site 0719)
- The First Hospital of Jilin University ( Site 0702)
- Jilin Cancer Hospital ( Site 0705)
- Shanghai Chest Hospital ( Site 0700)
- Zhongshan Hospital Fudan University ( Site 0712)
- Tangdu Hospital ( Site 0708)
- The First Affiliated Hospital of Xi an Jiaotong University ( Site 0709)
- Affiliated Tumor Hospital of Xinjiang Medical University ( Site 0701)
- The First Affiliated Hospital.Zhejiang University ( Site 0713)
- Sir Run Run Shaw Hospital School of Medicine, Zhejiang University ( Site 0715)
- Zhejiang Cancer Hospital ( Site 0716)
- Centre Leon Berard ( Site 0801)
- CHU Caen Service de Pneumologie ( Site 0804)
- Centre Georges Francois Leclerc ( Site 0809)
- Hopital Jean Minjoz Besancon ( Site 0805)
- Hopital Prive d'Antony ( Site 0811)
- C.H.U. de Tours - Hopital Bretonneau ( Site 0806)
- Centre D Oncologie de Gentilly ( Site 0810)
- Clinique Victor Hugo ( Site 0802)
- CHU Poitiers ( Site 0803)
- Robert Bosch Krankenhaus Klinik Schillerhoehe ( Site 0904)
- Universitaetsklinikum Mannheim ( Site 0911)
- Klinikum Wuerzburg Mitte gGmbH ( Site 0901)
- Pius Hospital Oldenburg ( Site 0905)
- Florence Nightingale Krankenhaus ( Site 0912)
- Kliniken Essen-Mitte ( Site 0900)
- Universitaetsklinikum Muenster ( Site 0906)
- Medizinische Fakultaet Carl Gustav Carus der TU Dresden ( Site 0907)
- Asklepios Klinikum Hamburg ( Site 0908)
- Hong Kong Integrated Oncology Centre ( Site 0304)
- Queen Mary Hospital ( Site 0301)
- Queen Mary Hospital ( Site 0303)
- Hong Kong United Oncology Centre ( Site 0306)
- Tuen Mun Hospital ( Site 0305)
- Barzilai Medical Center ( Site 1706)
- Soroka Medical Center ( Site 1702)
- Meir Medical Center ( Site 1701)
- Rabin Medical Center ( Site 1704)
- Ha Emek Medical Center ( Site 1707)
- Rambam Medical Center ( Site 1703)
- Chaim Sheba Medical Center. ( Site 1700)
- Sourasky Medical Center ( Site 1705)
- Istituto Europeo di Oncologia ( Site 1303)
- Ospedale San Vincenzo di Taormina ( Site 1302)
- AOU San Luigi Gonzaga di Orbassano ( Site 1300)
- IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 1305)
- Azienda Ospedaliero Universitaria Careggi ( Site 1301)
- Azienda Ospedaliera dei Colli V. Monaldi ( Site 1306)
- Universita Campus Bio-Medico di Roma ( Site 1304)
- National Hospital Organization Nagoya Medical Center ( Site 0608)
- Aichi Cancer Center Hospital ( Site 0612)
- Fujita Health University Hospital ( Site 0619)
- National Cancer Center Hospital East ( Site 0601)
- National Hospital Organization Shikoku Cancer Center ( Site 0616)
- Hyogo Cancer Center ( Site 0604)
- Kanazawa University Hospital ( Site 0617)
- Kanagawa Cancer Center ( Site 0609)
- Kansai Medical University Hospital ( Site 0606)
- Shizuoka Cancer Center Hospital and Research Institute ( Site 0602)
- National Hospital Organization Kyushu Medical Center ( Site 0621)
- Kyushu University Hospital ( Site 0605)
- Niigata Cancer Center Hospital ( Site 0610)
- Okayama University Hospital ( Site 0614)
- Osaka International Cancer Institute ( Site 0611)
- National Cancer Center Hospital ( Site 0603)
- Toranomon Hospital ( Site 0615)
- Tokyo Metropolitan Komagome Hospital ( Site 0618)
- Wakayama Medical University Hospital ( Site 0613)
- Chungbuk National University Hospital ( Site 0404)
- Gachon University Gil Medical Center ( Site 0408)
- National Cancer Center ( Site 0400)
- Seoul National University Bundang Hospital ( Site 0405)
- Seoul National University Hospital ( Site 0402)
- Asan Medical Center ( Site 0407)
- Samsung Medical Center ( Site 0403)
- The Catholic University of Korea. Seoul St. Mary s Hospital ( Site 0406)
- Ulsan University Hospital ( Site 0401)
- Instituto Jaliscience de Cancerologia ( Site 2000)
- Medica Sur S.A.B de C.V. ( Site 2003)
- Oaxaca Site Management Organization SC ( Site 2001)
- Instituto Nacional de Cancerologia. ( Site 2007)
- Hospitalo Univ. Germans Trias i Pujol ( Site 1100)
- Hospital de la Santa Creu i Sant Pau ( Site 1102)
- Hospital Universitari Vall d Hebron ( Site 1106)
- Hospital Ramon y Cajal ( Site 1101)
- Hospital Universitario 12 de Octubre ( Site 1103)
- Complejo Hospitalario Carlos Haya de Malaga ( Site 1107)
- Hospital Universitario Virgen Macarena ( Site 1104)
- Linkopings Universitetssjukhus ( Site 1504)
- Skanes Universitetssjukhus Lund ( Site 1503)
- Karolinska Universitetssjukhuset Solna ( Site 1500)
- Sahlgrenska Universitetssjukhuset ( Site 1502)
- Taipei Tzu Chi Hospital ( Site 0512)
- Changhua Christian Hospital ( Site 0509)
- National Taiwan University Hospital Hsin-Chu Branch ( Site 0511)
- Hualien Tzu Chi Medical Center-Hospital ( Site 0510)
- Kaohsiung Chang Gung Memorial Hospital ( Site 0507)
- Taipei Medical University Shuang Ho Hospital ( Site 0508)
- China Medical University Hospital ( Site 0505)
- Taichung Veterans General Hospital ( Site 0504)
- National Cheng Kung University Hospital ( Site 0506)
- National Taiwan University Hospital ( Site 0500)
- Mackay Memorial Hospital ( Site 0503)
- Taipei Veterans General Hospital ( Site 0501)
- Chang Gung Medical Foundation. Linkou ( Site 0502)
- Sussex University Hospitals ( Site 1003)
- Western General Hospital ( Site 1009)
- Leicester Royal Infirmary ( Site 1000)
- University College London Hospitals NHS Foundation Trust ( Site 1006)
- Chelsea & Westminster Hospital ( Site 1001)
- Birmingham Heartlands Hospital ( Site 1002)
- St James s University Hospital ( Site 1008)
- Barking Havering and Redbridge University Hospitals NHS Trust Queen s Hospital ( Site 1004)
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Pembro+Pemetrexed+Chemo
Placebo+Pemetrexed+Chemo
Participants receive pembrolizumab (pembro) 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles PLUS pemetrexed 500 mg/m^2 via IV infusion Q3W with no restrictions on the number of cycles PLUS platinum chemotherapy (chemo) (either carboplatin Area Under the Curve [AUC] 5 via IV infusion Q3W for 4 cycles [Cycles 1-4] or cisplatin 75 mg/m^2 via IV infusion Q3W for 4 cycles [Cycles 1-4]).
Participants receive normal saline solution via IV infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles PLUS pemetrexed 500 mg/m^2 via IV infusion Q3W with no restrictions on the number of cycles PLUS platinum chemotherapy (chemo)(either carboplatin AUC 5 via IV infusion Q3W for 4 cycles [Cycles 1-4] or cisplatin 75 mg/m^2 via IV infusion Q3W for 4 cycles [Cycles 1-4]).