A Study of Biomarker-Directed, Pembrolizumab (MK-3475) Based Combination Therapy for Advanced Non-Small Cell Lung Cancer (MK-3475-495/KEYNOTE-495)
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)
6 other identifiers
interventional
245
16 countries
81
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Oct 2018
Longer than P75 for phase_2
81 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 27, 2018
CompletedFirst Posted
Study publicly available on registry
May 7, 2018
CompletedStudy Start
First participant enrolled
October 1, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 13, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
June 13, 2025
CompletedJuly 1, 2025
June 1, 2025
6.7 years
April 27, 2018
June 29, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
ORR was defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: At least a 30% decrease in the sum of diameters \[SOD\] of target lesions, taking as reference the baseline sum diameters) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) as assessed by local site.
Up to ~2 years
Secondary Outcomes (4)
Progression Free Survival (PFS) per RECIST 1.1
Up to ~2 years
Overall Survival (OS)
Up to ~2 years
Number of Participants Experiencing Adverse Events (AEs)
Up to ~2 years
Number of Participants Discontinuing Study Drug Due to AEs
Up to ~2 years
Study Arms (12)
GEP low TMB low: Pembrolizumab + Quavonlimab
EXPERIMENTALParticipants receive pembrolizumab 200 mg Q3W plus quavonlimab at the Recommended Phase 2 Dose (\[RP2D\], dose and schedule based on study NCT03179436) until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years).
GEP low TMB low: Pembrolizumab + Favezelimab
EXPERIMENTALParticipants receive pembrolizumab 200 mg Q3W plus favezelimab 200 mg or 800 mg Q3W until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years).
GEP low TMB low: Pembrolizumab + Lenvatinib
EXPERIMENTALParticipants receive pembrolizumab 200 mg Q3W plus lenvatinib 20 mg once daily until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). Participants completing 35 infusions of pembrolizumab may continue with lenvatinib alone until disease progression or toxicity.
GEP low TMB hi: Pembrolizumab + Quavonlimab
EXPERIMENTALParticipants receive pembrolizumab 200 mg Q3W plus quavonlimab at the RP2D (dose and schedule based on study NCT03179436) until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years).
GEP low TMB hi: Pembrolizumab + Favezelimab
EXPERIMENTALParticipants receive pembrolizumab 200 mg Q3W plus favezelimab 200 mg or 800 mg Q3W until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years).
GEP low TMB hi: Pembrolizumab + Lenvatinib
EXPERIMENTALParticipants receive pembrolizumab 200 mg Q3W plus lenvatinib 20 mg once daily until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). Participants completing 35 infusions of pembrolizumab may continue with lenvatinib alone until disease progression or toxicity.
GEP hi TMB low: Pembrolizumab + Quavonlimab
EXPERIMENTALParticipants receive pembrolizumab 200 mg Q3W plus quavonlimab at the RP2D (dose and schedule based on study NCT03179436) until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years).
GEP hi TMB low: Pembrolizumab + Favezelimab
EXPERIMENTALParticipants receive pembrolizumab 200 mg Q3W plus favezelimab 200 mg or 800 mg Q3W until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years).
GEP hi TMB low: Pembrolizumab + Lenvatinib
EXPERIMENTALParticipants receive pembrolizumab 200 mg Q3W plus lenvatinib 20 mg once daily until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). Participants completing 35 infusions of pembrolizumab may continue with lenvatinib alone until disease progression or toxicity.
GEP hi TMB hi: Pembrolizumab + Quavonlimab
EXPERIMENTALParticipants receive pembrolizumab 200 mg Q3W plus quavonlimab at the RP2D (dose and schedule based on study NCT03179436) until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years).
GEP hi TMB hi: Pembrolizumab + Favezelimab
EXPERIMENTALParticipants receive pembrolizumab 200 mg Q3W plus favezelimab 200 mg or 800 mg Q3W until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years).
GEP hi TMB hi: Pembrolizumab + Lenvatinib
EXPERIMENTALParticipants receive pembrolizumab 200 mg Q3W plus lenvatinib 20 mg once daily until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). Participants completing 35 infusions of pembrolizumab may continue with lenvatinib alone until disease progression or toxicity.
Interventions
200 mg pembrolizumab solution for intravenous (IV) infusion administered Q3W
200 mg or 800 mg favezelimab solution for IV infusion administered Q3W
20 mg lenvatinib capsules administered orally once daily
Quavonlimab solution for IV infusion administered at the RP2D (dose and schedule based on study NCT03179436)
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (81)
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 8L6, Canada
Sunnybrook Health Science Centre ( Site 0304)
Toronto, Ontario, M4N 3M5, Canada
Princess Margaret Cancer Centre ( Site 0309)
Toronto, Ontario, M5G 2M9, Canada
CIUSSS du Saguenay-Lac-St-Jean ( Site 0305)
Chicoutimi, Quebec, G7H 5H6, Canada
Jewish General Hospital ( Site 0307)
Montreal, Quebec, H3T 1E2, Canada
CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 0310)
Montreal, Quebec, H3T 1M5, 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 K0Y5, Ireland
Mid Western Cancer Centre ( Site 2201)
Limerick, V94 YVH0, 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, Lombardy, 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, 104-0045, Japan
The Cancer Institute Hospital of JFCR ( Site 2000)
Tokyo, 135-8550, Japan
MED-POLONIA Sp. z o.o. ( Site 0907)
Poznan, Greater Poland Voivodeship, 60-693, Poland
Dolnoslaskie Centrum Onkologii. ( Site 0993)
Wroclaw, Lower Silesian Voivodeship, 53-413, Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
Warsaw, Masovian Voivodeship, 02-781, Poland
Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1003)
Ufa, Baskortostan, Respublika, 450054, Russia
The Loginov Moscow Clinical Scientific Center ( Site 1008)
Moscow, Moscow, 111123, Russia
N.N. Blokhin NMRCO ( Site 1000)
Moscow, Moscow, 115478, Russia
Budgetary Healthcare Institution of Omsk Region Clinical Oncology Dispensary-Chemotherapy #1 ( Site
Omsk, Omsk Oblast, 644013, Russia
SBHI Leningrad Regional Clinical Hospital ( Site 1001)
Saint Petersburg, Sankt-Peterburg, 194291, Russia
St Petersburg City Clinical Oncology Dispensary ( Site 1002)
Saint Petersburg, Sankt-Peterburg, 198255, Russia
Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1005)
Kazan', Tatarstan, Respublika, 420029, Russia
National Cancer Centre Singapore ( Site 1900)
Singapore, Central Singapore, 169610, Singapore
National University Hospital ( Site 1901)
Singapore, South West, 119074, 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
Seoul National University Bundang Hospital ( Site 0803)
Seongnam-si, Kyonggi-do, 13620, South Korea
Asan Medical Center ( Site 0801)
Songpa-gu, Seoul, 05505, South Korea
Seoul National University Hospital ( Site 0800)
Seoul, 03080, South Korea
Severance Hospital Yonsei University Health System ( Site 0802)
Seoul, 03722, South Korea
Samsung Medical Center ( Site 0805)
Seoul, 06351, South Korea
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)
Saint Gallen, Canton of Aargau, 9007, Switzerland
Universitaetsspital Basel ( Site 2104)
Basel, Canton of Basel-City, 4031, Switzerland
Hopitaux Universitaires de Geneve HUG ( Site 2106)
Geneva, Canton of Geneva, 1211, Switzerland
Universitaetsspital Zuerich ( Site 2100)
Zurich, Canton of Zurich, 8091, Switzerland
Kantonsspital Graubuenden ( Site 2103)
Chur, Kanton Graubünden, 7000, Switzerland
Kaohsiung Chang Gung Memorial Hospital ( Site 1203)
Kaohsiung City, 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 0QQ, United Kingdom
University College London Hospital NHS Foundation Trust ( Site 1308)
London, London, City of, NW1 2PG, United Kingdom
Derriford Hospital ( Site 1301)
Plymouth, PL6 8DH, United Kingdom
Related Publications (1)
Gutierrez M, Lam WS, Hellmann MD, Gubens MA, Aggarwal C, Tan DSW, Felip E, Chiu JWY, Lee JS, Yang JC, Garon EB, Finocchiaro G, Ahn MJ, Luft A, Landers GA, Basso A, Ma H, Kobie J, Palcza J, Cristescu R, Fong L, Snyder A, Yuan J, Herbst RS. Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results. Nat Med. 2023 Jul;29(7):1718-1727. doi: 10.1038/s41591-023-02385-6. Epub 2023 Jul 10.
PMID: 37429923RESULT
Related Links
MeSH Terms
Conditions
Interventions
Study Officials
- STUDY DIRECTOR
Medical Director
Merck Sharp & Dohme LLC
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 27, 2018
First Posted
May 7, 2018
Study Start
October 1, 2018
Primary Completion
June 13, 2025
Study Completion
June 13, 2025
Last Updated
July 1, 2025
Record last verified: 2025-06
Data Sharing
- IPD Sharing
- Will share
https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf