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

  • STATUS
    Recruiting
  • End date
    Feb 10, 2025
  • participants needed
    318
  • sponsor
    Merck Sharp & Dohme Corp.
Updated on 7 March 2021

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), MK-4280, or lenvatinib. The primary hypotheses are as follows: In participants receiving pembrolizumab in combination with either quavonlimab, MK-4280, 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.

Description

After Amendment 5, participants can receive 800 mg of MK-4280 every 3 weeks (Q3W)

Details
Condition Advanced Non Small Cell Lung Cancer
Treatment Pembrolizumab, Lenvatinib, MK-4280, MK-1308, Quavonlimab
Clinical Study IdentifierNCT03516981
SponsorMerck Sharp & Dohme Corp.
Last Modified on7 March 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Do you have any of these conditions: Do you have Advanced Non Small Cell Lung Cancer??
Do you have any of these conditions: Do you have Advanced Non Small Cell Lung Cancer??
Do you have any of these conditions: Do you have Advanced Non Small Cell Lung Cancer??
Do you have any of these conditions: Do you have Advanced Non Small Cell Lung Cancer??
Do you have any of these conditions: Do you have Advanced Non Small Cell Lung Cancer??
Do you have any of these conditions: Do you have Advanced Non Small Cell Lung Cancer??
Do you have any of these conditions: Do you have Advanced Non Small Cell Lung Cancer??
Do you have any of these conditions: Do you have Advanced Non Small Cell Lung Cancer??
Do you have any of these conditions: Do you have Advanced Non Small Cell Lung Cancer??
Do you have any of these conditions: Do you have Advanced Non Small Cell Lung Cancer??
Is your age greater than or equal to 18 yrs?
Do you have any of these conditions: Do you have Advanced Non Small Cell Lung Cancer??
Do you have any of these conditions: Do you have Advanced Non Small Cell Lung Cancer??
Do you have any of these conditions: Do you have Advanced Non Small Cell Lung Cancer??
Do you have any of these conditions: Do you have Advanced Non Small Cell Lung Cancer??
Do you have any of these conditions: Do you have Advanced Non Small Cell Lung Cancer??
Do you have any of these conditions: Do you have Advanced Non Small Cell Lung Cancer??
Do you have any of these conditions: Do you have Advanced Non Small Cell Lung Cancer??
Do you have Advanced Non Small Cell Lung Cancer?
Gender: Male or Female
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 vaccine within 30 days prior to 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, MK-4280, 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
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