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NCT03516981

PHASE2

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

Sponsor: Merck Sharp & Dohme LLC

View on ClinicalTrials.gov

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.

Official title: A Phase 2 Precision Oncology Study of Biomarker-Directed, Pembrolizumab-(MK-3475, SCH 900475) Based Combination Therapy for Advanced Non-Small Cell Lung Cancer (KEYNOTE-495; KeyImPaCT)

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

245

Start Date

2018-10-01

Completion Date

2025-06-13

Last Updated

2026-06-08

Healthy Volunteers

Conditions

Advanced Non-Small Cell Lung Cancer

Interventions

BIOLOGICAL

Pembrolizumab

200 mg pembrolizumab solution for intravenous (IV) infusion administered Q3W

BIOLOGICAL

Favezelimab

200 mg or 800 mg favezelimab solution for IV infusion administered Q3W

DRUG

Lenvatinib

20 mg lenvatinib capsules administered orally once daily

DRUG

Quavonlimab

Quavonlimab solution for IV infusion administered at the RP2D (dose and schedule based on study NCT03179436)

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.

Locations (81)

Arizona Oncology Associates, PC- HAL ( Site 8001)

Tempe, Arizona, United States

University of California Davis Comprehensive Cancer Center ( Site 0137)

Sacramento, California, United States

University of California San Francisco ( Site 0111)

San Francisco, California, United States

UCLA Hematology/Oncology -Santa Monica ( Site 0108)

Santa Monica, California, United States

Yale University School of Medicine ( Site 0100)

New Haven, Connecticut, United States

Mayo Clinic Florida ( Site 0115)

Jacksonville, Florida, United States

University of Maryland ( Site 0136)

Baltimore, Maryland, United States

Mayo Clinic Rochester - St. Mary's Hospital ( Site 0117)

Rochester, Minnesota, United States

John Theurer Cancer Center at Hackensack University Medical Center ( Site 0112)

Hackensack, New Jersey, United States

Memorial Sloan Kettering Cancer Center ( Site 0113)

New York, New York, United States

Weill Cornell Medical College ( Site 0138)

New York, New York, United States

Oncology Hematology Care ( Site 8005)

Cincinnati, Ohio, United States

University of Pennsylvania ( Site 0132)

Philadelphia, Pennsylvania, United States

UPMC Cancer Center/Hillman Cancer Center ( Site 0104)

Pittsburgh, Pennsylvania, United States

Texas Oncology-Memorial City ( Site 8006)

Houston, Texas, United States

Texas Oncology-Tyler ( Site 8003)

Tyler, Texas, United States

Emily Couric Clinical Cancer Center ( Site 0134)

Charlottesville, Virginia, United States

Northwest Cancer Specialists, P.C. ( Site 8000)

Vancouver, Washington, United States

University of Wisconsin- Madison Carbone Cancer Center ( Site 0130)

Madison, Wisconsin, United States

Blacktown Hospital Western Sydney Local Health District ( Site 0200)

Blacktown, New South Wales, Australia

Gallipoli Medical Research Foundation ( Site 0202)

Brisbane, Queensland, Australia

Fiona Stanley Hospital ( Site 0201)

Murdoch, Western Australia, Australia

The Ottawa Hospital ( Site 0306)

Ottawa, Ontario, Canada

Sunnybrook Health Science Centre ( Site 0304)

Toronto, Ontario, Canada

Princess Margaret Cancer Centre ( Site 0309)

Toronto, Ontario, Canada

CIUSSS du Saguenay-Lac-St-Jean ( Site 0305)

Chicoutimi, Quebec, Canada

Jewish General Hospital ( Site 0307)

Montreal, Quebec, Canada

CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 0310)

Montreal, Quebec, Canada

Prince of Wales Hospital ( Site 1801)

Hong Kong, Hong Kong

Queen Mary Hospital ( Site 1800)

Hong Kong, Hong Kong

St James Hospital ( Site 2200)

Dublin, Ireland

Mid Western Cancer Centre ( Site 2201)

Limerick, Ireland

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori ( Site 0702)

Meldola, Emilia-Romagna, Italy

Istituto Clinico Humanitas Research Hospital ( Site 0700)

Rozzano, Lombardy, Italy

AOU San Luigi Gonzaga di Orbassano ( Site 0707)

Orbassano, Torino, Italy

AULSS21 Regione Veneto Ospedale Mater Salutis - Legnago ( Site 0701)

Legnago, Verona, Italy

Azienda Ospedaliera Papardo ( Site 0706)

Messina, Italy

Seconda Universita degli Studi di Napoli ( Site 0704)

Naples, Italy

Fondazione Policlinico Universitario A. Gemelli ( Site 0703)

Roma, Italy

Azienda Ospedaliera Universitaria Senese ( Site 0705)

Siena, Italy

National Cancer Center Hospital ( Site 2001)

Tokyo, Japan

The Cancer Institute Hospital of JFCR ( Site 2000)

Tokyo, Japan

MED-POLONIA Sp. z o.o. ( Site 0907)

Poznan, Greater Poland Voivodeship, Poland

Dolnoslaskie Centrum Onkologii. ( Site 0993)

Wroclaw, Lower Silesian Voivodeship, Poland

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (

Warsaw, Masovian Voivodeship, Poland

Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1003)

Ufa, Baskortostan, Respublika, Russia

The Loginov Moscow Clinical Scientific Center ( Site 1008)

Moscow, Moscow, Russia

N.N. Blokhin NMRCO ( Site 1000)

Moscow, Moscow, Russia

Budgetary Healthcare Institution of Omsk Region Clinical Oncology Dispensary-Chemotherapy #1 ( Site

Omsk, Omsk Oblast, Russia

SBHI Leningrad Regional Clinical Hospital ( Site 1001)

Saint Petersburg, Sankt-Peterburg, Russia

St Petersburg City Clinical Oncology Dispensary ( Site 1002)

Saint Petersburg, Sankt-Peterburg, Russia

Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1005)

Kazan', Tatarstan, Respublika, Russia

National Cancer Centre Singapore ( Site 1900)

Singapore, Central Singapore, Singapore

National University Hospital ( Site 1901)

Singapore, South West, Singapore

MPOC ( Site 2310)

Groenkloof Pretoria, Gauteng, South Africa

Wits Clinical Research ( Site 2313)

Parktown-Johannesburg, Gauteng, South Africa

Univ. Pretoria and Steve Biko Academic Hospitals ( Site 2315)

Pretoria, Gauteng, South Africa

Sandton Oncology Medical Group PTY LTD ( Site 2316)

Sandton, Gauteng, South Africa

Vaal Triangle Oncology Centre ( Site 2314)

Vereeniging, Gauteng, South Africa

Umhlanga Oncolgy Center ( Site 2311)

Umhlanga, KwaZulu-Natal, South Africa

Cape Town Oncology Trials Pty Ltd ( Site 2312)

Kraaifontein, Western Cape, South Africa

Seoul National University Bundang Hospital ( Site 0803)

Seongnam-si, Kyonggi-do, South Korea

Asan Medical Center ( Site 0801)

Songpa-gu, Seoul, South Korea

Seoul National University Hospital ( Site 0800)

Seoul, South Korea

Severance Hospital Yonsei University Health System ( Site 0802)

Seoul, South Korea

Samsung Medical Center ( Site 0805)

Seoul, South Korea

Hospital General Universitari Vall d Hebron ( Site 1100)

Barcelona, Spain

Hospital Universitario Ramon y Cajal ( Site 1101)

Madrid, Spain

Hospital Universitario 12 de Octubre ( Site 1102)

Madrid, Spain

Kantonsspital St. Gallen ( Site 2102)

Saint Gallen, Canton of Aargau, Switzerland

Universitaetsspital Basel ( Site 2104)

Basel, Canton of Basel-City, Switzerland

Hopitaux Universitaires de Geneve HUG ( Site 2106)

Geneva, Canton of Geneva, Switzerland

Universitaetsspital Zuerich ( Site 2100)

Zurich, Canton of Zurich, Switzerland

Kantonsspital Graubuenden ( Site 2103)

Chur, Kanton Graubünden, Switzerland

Kaohsiung Chang Gung Memorial Hospital ( Site 1203)

Kaohsiung City, Taiwan

National Cheng Kung University Hospital ( Site 1202)

Tainan, Taiwan

National Taiwan University Hospital ( Site 1200)

Taipei, Taiwan

Taipei Veterans General Hospital ( Site 1204)

Taipei, Taiwan

Cambridge University Hospitals NHS Trust ( Site 1306)

Cambridge, Cambridgeshire, United Kingdom

University College London Hospital NHS Foundation Trust ( Site 1308)

London, London, City of, United Kingdom

Derriford Hospital ( Site 1301)

Plymouth, United Kingdom

Clinical Research Directory

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

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (81)