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 Clinical Trial

Official title:

A Randomized, Double-Blind, Phase 3 Study of Pemetrexed + Platinum Chemotherapy With or Without Pembrolizumab (MK-3475) in TKI-resistant EGFR-mutated Tumors in Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) Participants (KEYNOTE-789)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03515837
• Other study ID #: 3475-789
• Secondary ID: MK-3475-78918401
• Status: Completed
• Phase: Phase 3
• Start date: June 29, 2018
• Est. completion date: October 2, 2023

Study information

• Verified date: December 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Upon study completion, participants are discontinued and may be enrolled in a pembrolizumab extension study, if available.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 492
• Est. completion date: October 2, 2023
• Est. primary completion date: January 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Biological:
• pembrolizumab
IV infusion

Drug:
• pemetrexed
IV infusion
• carboplatin
IV infusion
• cisplatin
IV infusion
• saline solution
IV infusion

Locations

Country	Name	City	State
Australia	Eastern Health ( Site 0202)	Box Hill	Victoria
Australia	Chris OBrien Lifehouse ( Site 0200)	Camperdown	New South Wales
Australia	Austin Health ( Site 0203)	Heidelberg	Victoria
Australia	Westmead Hospital ( Site 0201)	Westmead	New South Wales
Brazil	Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 1911)	Barretos	Sao Paulo
Brazil	Hospital de Caridade de Ijui ( Site 1907)	Ijui	Rio Grande Do Sul
Brazil	Hospital Bruno Born ( Site 1913)	Lajeado	Rio Grande Do Sul
Brazil	Liga Norte Riograndense Contra o Cancer ( Site 1909)	Natal	Rio Grande Do Norte
Brazil	Hospital de Clinicas de Porto Alegre ( Site 1905)	Porto Alegre	Rio Grande Do Sul
Brazil	Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 1904)	Porto Alegre	Rio Grande Do Sul
Brazil	Hosp. Clinicas da Fac. de Medicina de Ribeirao Preto - USP ( Site 1912)	Ribeirao Preto	Sao Paulo
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 1903)	Sao Paulo
Canada	William Osler Health System ( Site 0100)	Brampton	Ontario
Canada	Jewish General Hospital ( Site 0105)	Montreal	Quebec
Canada	Princess Margaret Cancer Centre ( Site 0104)	Toronto	Ontario
Canada	Sunnybrook Health Sciences, Odette Cancer Centre ( Site 0102)	Toronto	Ontario
China	Beijing Cancer Hospital ( Site 0718)	Beijing	Beijing
China	Cancer Hospital Chinese Academy of Medical Sciences ( Site 0717)	Beijing	Beijing
China	Peking Union Medical College Hospital ( Site 0703)	Beijing	Beijing
China	The First Hospital of Jilin University ( Site 0702)	Chang chun	Jilin
China	Jilin Cancer Hospital ( Site 0705)	Changchun	Jilin
China	Hunan Cancer Hospital ( Site 0722)	Changsha	Hunan
China	Xiangya Hospital of Central South University ( Site 0710)	Changsha	Hunan
China	Southwest Hospital, The Third Military Medical University ( Site 0725)	Chongqing	Chongqing
China	Fujian Cancer Hospital ( Site 0723)	Fuzhou	Fujian
China	Sir Run Run Shaw Hospital School of Medicine, Zhejiang University ( Site 0715)	Hangzhou	Zhejiang
China	The First Affiliated Hospital.Zhejiang University ( Site 0713)	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital ( Site 0716)	Hangzhou	Zhejiang
China	The Affiliated Tumour Hospital of Harbin Medical University ( Site 0706)	Harbin	Heilongjiang
China	The First Affiliated Hospital of Anhui Medical University ( Site 0721)	Hefei	Anhui
China	Jiangsu Cancer Hospital ( Site 0719)	Nanjing	Jiangsu
China	Shanghai Chest Hospital ( Site 0700)	Shanghai	Shanghai
China	Zhongshan Hospital Fudan University ( Site 0712)	Shanghai	Shanghai
China	Affiliated Tumor Hospital of Xinjiang Medical University ( Site 0701)	Urumqi	Xinjiang
China	Tangdu Hospital ( Site 0708)	XI An	Shanxi
China	The First Affiliated Hospital of Xi an Jiaotong University ( Site 0709)	XI An	Shanxi
China	Henan Cancer Hospital ( Site 0711)	Zhengzhou	Henan
France	Hopital Prive d'Antony ( Site 0811)	Antony	Hauts-de-Seine
France	Hopital Jean Minjoz Besancon ( Site 0805)	Besancon	Doubs
France	CHU Caen Service de Pneumologie ( Site 0804)	Caen	Calvados
France	Centre Georges Francois Leclerc ( Site 0809)	Dijon	Cote-d'Or
France	Clinique Victor Hugo ( Site 0802)	Le Mans	Sarthe
France	Centre Leon Berard ( Site 0801)	Lyon	Auvergne
France	Centre D Oncologie de Gentilly ( Site 0810)	Nancy	Meurthe-et-Moselle
France	CHU Poitiers ( Site 0803)	Poitiers	Vienne
France	C.H.U. de Tours - Hopital Bretonneau ( Site 0806)	Tours	Indre-et-Loire
Germany	Medizinische Fakultaet Carl Gustav Carus der TU Dresden ( Site 0907)	Dresden	Sachsen
Germany	Florence Nightingale Krankenhaus ( Site 0912)	Duesseldorf	Nordrhein-Westfalen
Germany	Kliniken Essen-Mitte ( Site 0900)	Essen	Nordrhein-Westfalen
Germany	Robert Bosch Krankenhaus Klinik Schillerhoehe ( Site 0904)	Gerlingen	Baden-Wurttemberg
Germany	Asklepios Klinikum Hamburg ( Site 0908)	Hamburg
Germany	Universitaetsklinikum Mannheim ( Site 0911)	Mannheim	Baden-Wurttemberg
Germany	Universitaetsklinikum Muenster ( Site 0906)	Muenster	Nordrhein-Westfalen
Germany	Pius Hospital Oldenburg ( Site 0905)	Oldenburg	Niedersachsen
Germany	Klinikum Wuerzburg Mitte gGmbH ( Site 0901)	Wuerzburg	Bayern
Hong Kong	Hong Kong Integrated Oncology Centre ( Site 0304)	Hong Kong
Hong Kong	Queen Mary Hospital ( Site 0301)	Hong Kong
Hong Kong	Queen Mary Hospital ( Site 0303)	Hong Kong
Hong Kong	Hong Kong United Oncology Centre ( Site 0306)	Kowloon
Hong Kong	Tuen Mun Hospital ( Site 0305)	Tuen Mun
Israel	Ha Emek Medical Center ( Site 1707)	Afula	HaTsafon
Israel	Barzilai Medical Center ( Site 1706)	Ashkelon	HaDarom
Israel	Soroka Medical Center ( Site 1702)	Beer-Sheva	HaDarom
Israel	Rambam Medical Center ( Site 1703)	Haifa	Heifa
Israel	Meir Medical Center ( Site 1701)	Kfar-Saba	HaMerkaz
Israel	Rabin Medical Center ( Site 1704)	Petah Tikva	HaMerkaz
Israel	Chaim Sheba Medical Center. ( Site 1700)	Ramat Gan	Tell Abib
Israel	Sourasky Medical Center ( Site 1705)	Tel Aviv	Tell Abib
Italy	IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 1305)	Bari
Italy	Azienda Ospedaliero Universitaria Careggi ( Site 1301)	Firenze
Italy	Istituto Europeo di Oncologia ( Site 1303)	Milano	Lombardia
Italy	Azienda Ospedaliera dei Colli V. Monaldi ( Site 1306)	Napoli
Italy	AOU San Luigi Gonzaga di Orbassano ( Site 1300)	Orbassano	Torino
Italy	Universita Campus Bio-Medico di Roma ( Site 1304)	Roma
Italy	Ospedale San Vincenzo di Taormina ( Site 1302)	Taormina	Messina
Japan	Hyogo Cancer Center ( Site 0604)	Akashi	Hyogo
Japan	Kyushu University Hospital ( Site 0605)	Fukuoka
Japan	National Hospital Organization Kyushu Medical Center ( Site 0621)	Fukuoka
Japan	Kansai Medical University Hospital ( Site 0606)	Hirakata	Osaka
Japan	Kanazawa University Hospital ( Site 0617)	Kanazawa	Ishikawa
Japan	National Cancer Center Hospital East ( Site 0601)	Kashiwa	Chiba
Japan	National Hospital Organization Shikoku Cancer Center ( Site 0616)	Matsuyama	Ehime
Japan	Aichi Cancer Center Hospital ( Site 0612)	Nagoya	Aichi
Japan	National Hospital Organization Nagoya Medical Center ( Site 0608)	Nagoya	Aichi
Japan	Niigata Cancer Center Hospital ( Site 0610)	Niigata
Japan	Okayama University Hospital ( Site 0614)	Okayama
Japan	Osaka International Cancer Institute ( Site 0611)	Osaka
Japan	Shizuoka Cancer Center Hospital and Research Institute ( Site 0602)	Sunto-gun	Shizuoka
Japan	National Cancer Center Hospital ( Site 0603)	Tokyo
Japan	Tokyo Metropolitan Komagome Hospital ( Site 0618)	Tokyo
Japan	Toranomon Hospital ( Site 0615)	Tokyo
Japan	Fujita Health University Hospital ( Site 0619)	Toyoake	Aichi
Japan	Wakayama Medical University Hospital ( Site 0613)	Wakayama
Japan	Kanagawa Cancer Center ( Site 0609)	Yokohama	Kanagawa
Korea, Republic of	Chungbuk National University Hospital ( Site 0404)	Cheongju si	Chungcheongbuk-do [Chungbuk]
Korea, Republic of	National Cancer Center ( Site 0400)	Gyeonggi-do	Kyonggi-do
Korea, Republic of	Gachon University Gil Medical Center ( Site 0408)	Incheon	Incheon-gwangyeoksi [Incheon]
Korea, Republic of	Seoul National University Bundang Hospital ( Site 0405)	Seongnam-si	Kyonggi-do
Korea, Republic of	Asan Medical Center ( Site 0407)	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Samsung Medical Center ( Site 0403)	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Seoul National University Hospital ( Site 0402)	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	The Catholic University of Korea. Seoul St. Mary s Hospital ( Site 0406)	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Ulsan University Hospital ( Site 0401)	Ulsan	Ulsan-Kwangyokshi
Mexico	Instituto Jaliscience de Cancerologia ( Site 2000)	Guadalajara	Jalisco
Mexico	Medica Sur S.A.B de C.V. ( Site 2003)	Mexico City
Mexico	Oaxaca Site Management Organization SC ( Site 2001)	Oaxaca
Mexico	Instituto Nacional de Cancerologia. ( Site 2007)	Tlalpan
Spain	Hospitalo Univ. Germans Trias i Pujol ( Site 1100)	Badalona	Barcelona [Barcelona]
Spain	Hospital de la Santa Creu i Sant Pau ( Site 1102)	Barcelona	Barcelona [Barcelona]
Spain	Hospital Universitari Vall d Hebron ( Site 1106)	Barcelona	Barcelona [Barcelona]
Spain	Hospital Ramon y Cajal ( Site 1101)	Madrid
Spain	Hospital Universitario 12 de Octubre ( Site 1103)	Madrid
Spain	Complejo Hospitalario Carlos Haya de Malaga ( Site 1107)	Malaga
Spain	Hospital Universitario Virgen Macarena ( Site 1104)	Sevilla
Sweden	Sahlgrenska Universitetssjukhuset ( Site 1502)	Goteborg	Vastra Gotalands Lan [se-14]
Sweden	Linkopings Universitetssjukhus ( Site 1504)	Linkoping	Ostergotlands Lan [se-05]
Sweden	Skanes Universitetssjukhus Lund ( Site 1503)	Lund	Skane Lan [se-12]
Sweden	Karolinska Universitetssjukhuset Solna ( Site 1500)	Solna	Stockholms Lan [se-01]
Taiwan	Changhua Christian Hospital ( Site 0509)	Changhua
Taiwan	National Taiwan University Hospital Hsin-Chu Branch ( Site 0511)	Hsinchu
Taiwan	Hualien Tzu Chi Medical Center-Hospital ( Site 0510)	Hualien
Taiwan	Kaohsiung Chang Gung Memorial Hospital ( Site 0507)	Kaohsiung
Taiwan	Taipei Medical University Shuang Ho Hospital ( Site 0508)	New Taipei
Taiwan	Taipei Tzu Chi Hospital ( Site 0512)	New Taipei City	New Taipei
Taiwan	China Medical University Hospital ( Site 0505)	Taichung
Taiwan	Taichung Veterans General Hospital ( Site 0504)	Taichung
Taiwan	National Cheng Kung University Hospital ( Site 0506)	Tainan
Taiwan	Mackay Memorial Hospital ( Site 0503)	Taipei
Taiwan	National Taiwan University Hospital ( Site 0500)	Taipei
Taiwan	Taipei Veterans General Hospital ( Site 0501)	Taipei
Taiwan	Chang Gung Medical Foundation. Linkou ( Site 0502)	Taoyuan
United Kingdom	Birmingham Heartlands Hospital ( Site 1002)	Birmingham
United Kingdom	Sussex University Hospitals ( Site 1003)	Brighton	Brighton And Hove
United Kingdom	Western General Hospital ( Site 1009)	Edinburgh	Edinburgh, City Of
United Kingdom	St James s University Hospital ( Site 1008)	Leeds
United Kingdom	Leicester Royal Infirmary ( Site 1000)	Leicester	Leicestershire
United Kingdom	Chelsea & Westminster Hospital ( Site 1001)	London	London, City Of
United Kingdom	University College London Hospitals NHS Foundation Trust ( Site 1006)	London	London, City Of
United Kingdom	Barking Havering and Redbridge University Hospitals NHS Trust Queen s Hospital ( Site 1004)	Romford
United States	New York Oncology Hematology P.C ( Site 8000)	Albany	New York
United States	Emily Couric Clinical Cancer Center ( Site 0020)	Charlottesville	Virginia
United States	Parkland Health & Hospital System ( Site 2102)	Dallas	Texas
United States	University of Texas Southwestern Medical Center at Dallas ( Site 0035)	Dallas	Texas
United States	Southdale Cancer Care, University of Minnesota Medical Center- Edina ( Site 0048)	Edina	Minnesota
United States	North Shore University Health System ( Site 0030)	Evanston	Illinois
United States	Saint Lukes Hospital of Kansas City ( Site 0060)	Kansas City	Missouri
United States	Monter Cancer Center ( Site 0054)	Lake Success	New York
United States	Cedars-Sinai Medical Center ( Site 0070)	Los Angeles	California
United States	Froedtert Hospital & the Medical College of Wisconsin ( Site 0041)	Milwaukee	Wisconsin
United States	Pacific Cancer Care ( Site 0058)	Monterey	California
United States	Memorial Sloan Kettering Cancer Center-Rockerfeller Patient Pavilion ( Site 0049)	New York	New York
United States	UC Irvine Medical Center/Chao Family Comprehensive Cancer Center ( Site 0092)	Orange	California
United States	Kaiser Permanente Northwest ( Site 0037)	Portland	Oregon
United States	Providence Portland Medical Center ( Site 0097)	Portland	Oregon
United States	Utah Cancer Specialists ( Site 0001)	Salt Lake City	Utah
United States	St. Joseph Heritage Healthcare ( Site 0003)	Santa Rosa	California
United States	Siouxland Regioinal Cancer Center dba June E. Nylen Cancer Center ( Site 0065)	Sioux City	Iowa
United States	White Plains Hospital Center for Cancer Care ( Site 0014)	White Plains	New York

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  China,  France,  Germany,  Hong Kong,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. PFS was assessed by blinded independent central review (BICR) using RECIST 1.1. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions is also considered PD. The PFS presented was analyzed using the product-limit (Kaplan-Meier) method for censored data.	Up to ~40 months
Primary	Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis will be censored at the date of the last follow-up. The OS presented was analyzed using the product-limit (Kaplan-Meier) method for censored data.	Up to ~51 months
Secondary	Objective Response Rate (ORR) Per RECIST 1.1	ORR was assessed by BICR using RECIST 1.1. ORR is defined as the percentage of participants in the analysis population who experience a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The ORR for participants is presented.	Up to ~51 months
Secondary	Duration of Response (DOR) Per RECIST 1.1	DOR was assessed by BICR using RECIST 1.1. For participants who experience a response of CR or PR, DOR is defined as the time from the earliest date of qualifying response until earliest date of PD or death from any cause, whichever comes first. The DOR presented was analyzed using the product-limit (Kaplan-Meier) method for censored data.	Up to ~51 months
Secondary	Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 Item (QLQ-C30) Global Health Status (Item 29) Scale Score	The EORTC QLQ-C30 is a 30-item Patient Reported Outcome (PRO) questionnaire developed to assess the quality of life of cancer patients. For Global Health Status, participants are asked "How would you rate your overall health during the past week?" Individual responses are given on a 7-point scale (1=Very poor; 7=Excellent), with a higher score indicating a better outcome. The change from baseline in EORTC-QLQ-C30 score for Global Health Status is presented.	Baseline and Week 18
Secondary	Time to True Deterioration (TTD) in the EORTC Questionnaire Composite Endpoint of Cough, Chest Pain or Dyspnea	TTD is the time from baseline to first onset of 10 points or more deterioration from baseline with confirmation by the subsequent visit of 10 points or more deterioration from baseline in the composite endpoint of cough [EORTC QLQ-Lung Cancer Module 13 (LC13) Item 1; How much did you cough?], chest pain [EORTC QLQ-LC13 Item 10; Have you had pain in your chest?], or dyspnea [EORTC QLQ-C30 Item 8; Were you short of breath?]. Individual responses are given on a 4-point scale (1=Not at all; 4=Very much), with a lower score indicating a better outcome. The TTD was analyzed using the product-limit (Kaplan-Meier) method for censored data. The time to true deterioration in the composite endpoint of cough, chest pain or dyspnea is presented.	Baseline and up to ~51 months
Secondary	Percentage of Participants Who Experienced an Adverse Event (AE)	An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. The percentage of participants who experienced an AE is presented.	Up to ~44 months
Secondary	Percentage of Participants Who Discontinued Study Treatment Due to AEs	An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. The percentage of participants who discontinued study treatment due to an adverse event is presented.	Up to ~41 months
Secondary	Change From Baseline in EORTC-QLQ-C30 Quality of Life (Item 30) Scale Score	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. For Quality of Life, participants are asked "How would you rate your overall quality of life during the past week?" Individual responses are given on a 7-point scale (1=Very poor; 7=Excellent), with a higher score indicating a better outcome. The change from baseline in EORTC-QLQ-C30 score for Quality of Life is presented.	Baseline and Week 18

External Links

•   Merck Clinical Trials Information