Lung Cancer Clinical Trial

A Study of Biomarker-Directed, Pembrolizumab (MK-3475) Based Combination Therapy for Advanced Non-Small Cell Lung Cancer (MK-3475-495/KEYNOTE-495)

Summary

This study will investigate the utility of biomarker-based triage for study participants with advanced non-small cell lung cancer (NSCLC) without prior systemic therapy. Study participants within groups defined by a biomarker-based classifier (gene expression profile [GEP] and tumor mutational burden [TMB]) will be randomized to receive pembrolizumab in combination with quavonlimab (MK-1308), favezelimab (MK-4280), or lenvatinib. The primary hypotheses are as follows: In participants receiving pembrolizumab in combination with either quavonlimab, favezelimab, or lenvatinib, the Objective Response Rate (ORR) will be 1) greater than 5% among participants with low GEP and low TMB, 2) greater than 20% among participants with low GEP and high TMB, 3) greater than 20% among participants with high GEP and low TMB, and 4) greater than 45% among participants with high GEP and high TMB.

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Full Description

After Amendment 5, participants can receive 800 mg of favezelimab every 3 weeks (Q3W)

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Has a histologically- or cytologically-confirmed diagnosis of Stage IV (American Joint Committee on Cancer [AJCC] v 8) NSCLC and has not had prior systemic therapy for advanced disease
Has confirmation that epidermal growth factor receptor- (EGFR-), anaplastic lymphoma kinase- (ALK-), c-ros oncogene 1- (ROS1-), or B isoform of rapidly accelerated fibrosarcoma- (B-Raf-) directed therapy is not indicated as primary therapy (documentation of absence of tumor activating EGFR mutations, B-Raf mutations, ALK gene rearrangements, and ROS1 gene rearrangements)
Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology
Male participants must agree to use contraception during the treatment period and for ≥120 days, after the last dose of study treatment and refrain from donating sperm during this period. Male participants with pregnant partners must agree to use a condom
Female participants eligible to participate if not pregnant, not breastfeeding, and not a woman of childbearing potential (WOCBP) or is a WOCBP who agrees to follow contraceptive guidance during the treatment period and for ≥120 days after the last dose of study treatment
Provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
Has adequate organ function

Exclusion Criteria:

Has significant cardiovascular impairment within 12 months of the first dose of study drug: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident (CVA) stroke, or cardiac arrhythmia associated with hemodynamic instability, significant cardiovascular impairment, or a left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multigated acquisition scan (MUGA) or echocardiogram
Prolongation of QTc interval to >480 milliseconds (ms)
Has symptomatic ascites or pleural effusion
Has had an allogenic tissue/solid organ transplant
WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study treatment
Has not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy, or has had major surgery within 3 weeks prior to first dose of study intervention
Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula, gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
Radiographic evidence of major blood vessel invasion/infiltration
Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
Has received prior systemic chemotherapy treatment for metastatic/recurrent NSCLC
Has current NSCLC disease that can be treated with curative intent with surgical resection, localized radiotherapy, or chemoradiation
Is expected to require any other form of systemic or localized antineoplastic therapy while on study (including maintenance therapy with another agent for NSCLC, radiation therapy, and/or surgical resection)
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
Has received previous treatment with another agent targeting the Lymphocyte-activation gene 3 (LAG-3) receptor
Has received previous treatment with another agent targeting vascular endothelial growth factor (VEGF) or the VEGF receptor
Has received prior anticancer therapy including investigational agents within 4 weeks prior to randomization
Has received prior radiotherapy within 2 weeks of start of study treatment or received lung radiation therapy of >30 Gy within 6 months prior to the first dose of study intervention
Has received a live or live-attenuated vaccine within 30 days before the first dose of study treatment
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.
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
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Has severe hypersensitivity (≥Grade 3) to pembrolizumab, favezelimab, or lenvatinib and/or any of its excipients
Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs)
Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
Has an active infection requiring systemic therapy
Has a known history of human immunodeficiency virus (HIV) infection
Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days (females and males) after the last dose of study treatment.

Study is for people with:

Lung Cancer

Phase:

Phase 2

Estimated Enrollment:

318

Study ID:

NCT03516981

Recruitment Status:

Active, not recruiting

Sponsor:

Merck Sharp & Dohme LLC

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There are 78 Locations for this study

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Arizona Oncology Associates, PC- HAL ( Site 8001)
Tempe Arizona, 85284, United States
University of California Davis Comprehensive Cancer Center ( Site 0137)
Sacramento California, 95817, United States
University of California San Francisco ( Site 0111)
San Francisco California, 94143, United States
UCLA Hematology/Oncology -Santa Monica ( Site 0108)
Santa Monica California, 90404, United States
Yale University School of Medicine ( Site 0100)
New Haven Connecticut, 06520, United States
Mayo Clinic Florida ( Site 0115)
Jacksonville Florida, 32224, United States
University of Maryland ( Site 0136)
Baltimore Maryland, 21201, United States
Mayo Clinic Rochester - St. Mary's Hospital ( Site 0117)
Rochester Minnesota, 55905, United States
John Theurer Cancer Center at Hackensack University Medical Center ( Site 0112)
Hackensack New Jersey, 07601, United States
Memorial Sloan Kettering Cancer Center ( Site 0113)
New York New York, 10065, United States
Weill Cornell Medical College ( Site 0138)
New York New York, 10065, United States
Oncology Hematology Care ( Site 8005)
Cincinnati Ohio, 45242, United States
University of Pennsylvania ( Site 0132)
Philadelphia Pennsylvania, 19104, United States
UPMC Cancer Center/Hillman Cancer Center ( Site 0104)
Pittsburgh Pennsylvania, 15232, United States
Texas Oncology-Memorial City ( Site 8006)
Houston Texas, 77024, United States
Texas Oncology-Tyler ( Site 8003)
Tyler Texas, 75702, United States
Emily Couric Clinical Cancer Center ( Site 0134)
Charlottesville Virginia, 22903, United States
Northwest Cancer Specialists, P.C. ( Site 8000)
Vancouver Washington, 98684, United States
University of Wisconsin- Madison Carbone Cancer Center ( Site 0130)
Madison Wisconsin, 53792, United States
Blacktown Hospital Western Sydney Local Health District ( Site 0200)
Blacktown New South Wales, 2148, Australia
Gallipoli Medical Research Foundation ( Site 0202)
Brisbane Queensland, 4120, Australia
Fiona Stanley Hospital ( Site 0201)
Murdoch Western Australia, 6150, Australia
The Ottawa Hospital ( Site 0306)
Ottawa Ontario, K1H 8, Canada
Sunnybrook Health Science Centre ( Site 0304)
Toronto Ontario, M4N 3, Canada
Princess Margaret Cancer Centre ( Site 0309)
Toronto Ontario, M5G 2, Canada
CIUSSS du Saguenay-Lac-St-Jean ( Site 0305)
Chicoutimi Quebec, G7H 5, Canada
Jewish General Hospital ( Site 0307)
Montreal Quebec, H3T 1, Canada
CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 0310)
Montreal Quebec, H3T 1, Canada
Prince of Wales Hospital ( Site 1801)
Hong Kong , 000, Hong Kong
Queen Mary Hospital ( Site 1800)
Hong Kong , , Hong Kong
St James Hospital ( Site 2200)
Dublin , D08 K, Ireland
Mid Western Cancer Centre ( Site 2201)
Limerick , V94 Y, Ireland
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori ( Site 0702)
Meldola Emilia-Romagna, 47014, Italy
Istituto Clinico Humanitas Research Hospital ( Site 0700)
Rozzano Lombardia, 20089, Italy
AOU San Luigi Gonzaga di Orbassano ( Site 0707)
Orbassano Torino, 10043, Italy
AULSS21 Regione Veneto Ospedale Mater Salutis - Legnago ( Site 0701)
Legnago Verona, 37045, Italy
Azienda Ospedaliera Papardo ( Site 0706)
Messina , 98158, Italy
Seconda Universita degli Studi di Napoli ( Site 0704)
Napoli , 80131, Italy
Fondazione Policlinico Universitario A. Gemelli ( Site 0703)
Roma , 00168, Italy
Azienda Ospedaliera Universitaria Senese ( Site 0705)
Siena , 53100, Italy
National Cancer Center Hospital ( Site 2001)
Tokyo , 104-0, Japan
The Cancer Institute Hospital of JFCR ( Site 2000)
Tokyo , 135-8, Japan
Seoul National University Bundang Hospital ( Site 0803)
Seongnam-si Kyonggi-do, 13620, Korea, Republic of
Asan Medical Center ( Site 0801)
Songpa-gu Seoul, 05505, Korea, Republic of
Seoul National University Hospital ( Site 0800)
Seoul , 03080, Korea, Republic of
Severance Hospital Yonsei University Health System ( Site 0802)
Seoul , 03722, Korea, Republic of
Samsung Medical Center ( Site 0805)
Seoul , 06351, Korea, Republic of
Dolnoslaskie Centrum Onkologii. ( Site 0993)
Wroclaw Dolnoslaskie, 53-41, Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
Warszawa Mazowieckie, 02-78, Poland
MED-POLONIA Sp. z o.o. ( Site 0907)
Poznan Wielkopolskie, 60-69, Poland
Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1003)
Ufa Baskortostan, Respublika, 45005, Russian Federation
The Loginov Moscow Clinical Scientific Center ( Site 1008)
Moscow Moskva, 11112, Russian Federation
N.N. Blokhin NMRCO ( Site 1000)
Moscow Moskva, 11547, Russian Federation
Budgetary Healthcare Institution of Omsk Region Clinical Oncology Dispensary-Chemotherapy #1 ( Site
Omsk Omskaya Oblast, 64401, Russian Federation
SBHI Leningrad Regional Clinical Hospital ( Site 1001)
Saint Petersburg Sankt-Peterburg, 19429, Russian Federation
St Petersburg City Clinical Oncology Dispensary ( Site 1002)
St. Petersburg Sankt-Peterburg, 19825, Russian Federation
Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1005)
Kazan Tatarstan, Respublika, 42002, Russian Federation
National Cancer Centre Singapore ( Site 1900)
Singapore Central Singapore, 16961, Singapore
National University Hospital ( Site 1901)
Singapore South West, 11907, Singapore
MPOC ( Site 2310)
Groenkloof Pretoria Gauteng, 0181, South Africa
Wits Clinical Research ( Site 2313)
Parktown-Johannesburg Gauteng, 2193, South Africa
Univ. Pretoria and Steve Biko Academic Hospitals ( Site 2315)
Pretoria Gauteng, 0002, South Africa
Sandton Oncology Medical Group PTY LTD ( Site 2316)
Sandton Gauteng, 2196, South Africa
Vaal Triangle Oncology Centre ( Site 2314)
Vereeniging Gauteng, 1939, South Africa
Umhlanga Oncolgy Center ( Site 2311)
Umhlanga Kwazulu-Natal, 4320, South Africa
Cape Town Oncology Trials Pty Ltd ( Site 2312)
Kraaifontein Western Cape, 7570, South Africa
Hospital General Universitari Vall d Hebron ( Site 1100)
Barcelona , 08035, Spain
Hospital Universitario Ramon y Cajal ( Site 1101)
Madrid , 28034, Spain
Hospital Universitario 12 de Octubre ( Site 1102)
Madrid , 28041, Spain
Kantonsspital St. Gallen ( Site 2102)
St. Gallen Aargau, 9007, Switzerland
Universitaetsspital Basel ( Site 2104)
Basel Basel-Stadt, 4031, Switzerland
Hopitaux Universitaires de Geneve HUG ( Site 2106)
Geneva Geneve, 1211, Switzerland
Kantonsspital Graubuenden ( Site 2103)
Chur Grisons, 7000, Switzerland
Universitaetsspital Zuerich ( Site 2100)
Zuerich Zurich, 8091, Switzerland
Kaohsiung Chang Gung Memorial Hospital ( Site 1203)
Kaohsiung , 83301, Taiwan
National Cheng Kung University Hospital ( Site 1202)
Tainan , 704, Taiwan
National Taiwan University Hospital ( Site 1200)
Taipei , 10048, Taiwan
Taipei Veterans General Hospital ( Site 1204)
Taipei , 11217, Taiwan
Cambridge University Hospitals NHS Trust ( Site 1306)
Cambridge Cambridgeshire, CB2 0, United Kingdom
University College London Hospital NHS Foundation Trust ( Site 1308)
London London, City Of, NW1 2, United Kingdom
Derriford Hospital ( Site 1301)
Plymouth , PL6 8, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Lung Cancer

Phase:

Phase 2

Estimated Enrollment:

318

Study ID:

NCT03516981

Recruitment Status:

Active, not recruiting

Sponsor:


Merck Sharp & Dohme LLC

How clear is this clinincal trial information?

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