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KEYMAKER-U01 Umbrella Master Study: Studies of Investigational Agents With Either Pembrolizumab (MK-3475) Alone or With Pembrolizumab PLUS Chemotherapy in Participants With Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-U01/KEYMAKER-U01)

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ClinicalTrials.gov Identifier: NCT04165798
Recruitment Status : Recruiting
First Posted : November 18, 2019
Last Update Posted : June 11, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:

This study is referred to as the "umbrella master protocol" for pembrolizumab (MK-3475) in the treatment of non-small cell lung cancer (NSCLC). This pembrolizumab NSCLC umbrella master protocol uses a platform design and consists of this master screening study and three substudies. Each substudy will enroll a different population of NSCLC participants.

The goal of this umbrella master protocol is to screen potential participants with NSCLC for enrollment into 1 of 3 substudies. Participants must first enroll in this pembrolizumab master protocol study and undergo screening for NSCLC that will be used to assign them to participation in 1 of 3 pembrolizumab substudies.


Condition or disease Intervention/treatment
Carcinoma, Non-Small-Cell Lung Diagnostic Test: Tumor Imaging Procedure: Tumor Tissue Collection Procedure: Blood Sample Collection

Detailed Description:

The following 3 pembrolizumab substudies will evaluate the efficacy of different investigational agents in combination with pembrolizumab given in sequence or in combination with pembrolizumab PLUS chemotherapy:

  • KEYMAKER-U01 Substudy 1: A Phase 2, Umbrella Study with Rolling Arms of Investigational Agents with Pembrolizumab in Combination with Chemotherapy in Treatment-Naïve Patients with Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A) - NCT04165070
  • KEYMAKER-U01 Substudy 2: A Phase 2, Umbrella Study with Rolling Arms of Investigational Agents in Combination with Pembrolizumab in Treatment Naïve Patients with PD-L1 Positive Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-01B) - NCT04165083
  • KEYMAKER-U01 Substudy 3: A Phase 2, Umbrella Study with Rolling Arms of Investigational Agents in Combination with Pembrolizumab in Patients with Advanced Non-small Cell Lung Cancer (NSCLC) Previously Treated with anti-PD-(L)1 Therapy (MK-3475-01C) - NCT04165096

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Study Type : Observational
Estimated Enrollment : 260 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: KEYMAKER-U01 Master Study: A Phase 2, Umbrella Study With Rolling Arms of Investigational Agents With Either Pembrolizumab in Combination With Chemotherapy or With Pembrolizumab Alone in Patients With Advanced Non-small Cell Lung Cancer (NSCLC)
Actual Study Start Date : December 19, 2019
Estimated Primary Completion Date : February 13, 2032
Estimated Study Completion Date : February 13, 2032

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Prospective NSCLC Participants
Male and female participants with histologically-confirmed diagnosis of squamous or nonsquamous NSCLC will be screened for participation in 1 of 3 pembrolizumab substudies.
Diagnostic Test: Tumor Imaging
Participants will undergo tumor imaging using either a magnetic resonance imaging (MRI) scan or a computed tomography (CT) scan.

Procedure: Tumor Tissue Collection
Participants without archival tumor tissue samples will undergo tumor tissue collection for newly obtained tumor tissue.

Procedure: Blood Sample Collection

Participants will have blood samples drawn for analysis of:

  • genetics
  • ribonucleic acid (RNA)
  • serum biomarker
  • plasma biomarker
  • circulating tumor DNA (ctDNA)




Primary Outcome Measures :
  1. Programmed Cell Death-Ligand 1 (PD-L1) Tumor Expression Level: Tumor Proportion Score (TPS) <1% vs. TPS =1% [ Time Frame: Up to approximately 1 month ]
    Participants' tumors will be evaluated for their PD-L1 tumor expression level using archival tumor tissue samples or newly obtained tumor tissue. The percentage of participants who have a Tumor Proportion Score (TPS) <1% vs. a TPS =1% will be presented.

  2. Tumor Histology Status: Squamous Non-small Cell Lung Cancer (NSCLC) vs. Nonsquamous NSCLC [ Time Frame: Up to approximately 1 month ]
    Participants' tumors will be evaluated for their tumor histology status as being either squamous vs. nonsquamous NSCLC using archival or newly obtained tumor tissue samples. The percentage of participants who have squamous vs. nonsquamous NSCLC will be presented.


Biospecimen Retention:   Samples With DNA

To identify novel biomarkers, biospecimens (i.e., blood components, tumor material) will be collected to support analyses of cellular components (eg, protein, DNA, RNA, metabolites) and other circulating molecules.

Investigations may include but are not limited to:

Germline (blood) genetic analyses (e.g. single nucleotide polymorphism [SNP] analyses, whole exome sequencing, whole genome sequencing)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Male and female participants with histologically-confirmed diagnosis of squamous or nonsquamous NSCLC
Criteria

Inclusion Criteria:

  • Has histologically- or cytologically-confirmed diagnosis of Stage IV squamous or nonsquamous NSCLC
  • Participants with nonsquamous NSCLC who are not eligible for an approved targeted therapy
  • Is able to to provide archival tumor tissue sample collected either within 5 years or within the interval from completion of last treatment but before entering the screening period or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated obtained within 90 days of treatment initiation
  • Has not received prior systemic treatment for their metastatic NSCLC
  • Is able to complete all screening procedures within the 35-day screening window
  • Has adequate organ function within 10 days of initiation of study treatment
  • Male participants must agree to use contraception and should refrain from donating sperm during the treatment period and:
  • Substudy 1: for at least 120 days after the last dose of pembrolizumab and for at least 180 days after the last dose of chemotherapy
  • Substudies 2 and 3: for at least 120 days after study treatments
  • Female participants must not be pregnant or breastfeeding, and at least 1 of the following conditions apply:

    1. Not a woman of childbearing potential (WOCBP), OR
    2. A WOCBP who agrees to use contraception during the treatment period and:
  • Substudy 1: for at least 120 days after the last dose of pembrolizumab and for at least 180 days after the last dose of chemotherapy.
  • Substudies 2 and 3: for at least 120 days after study treatment

    *Substudies 1 and 2 Only:

  • Has not received prior systemic treatment for their metastatic NSCLC

    *Substudy 2 Only:

  • Has a programmed death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥1%

    *Substudy 3 Only:

  • Has progressed on treatment with an anti-PD-(L)1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies
  • Has progressive disease during/after platinum doublet chemotherapy

Exclusion Criteria:

  • Has a diagnosis of small cell lung cancer
  • 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 before the first dose of study treatment
  • Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years
  • Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
  • Has an active infection requiring systemic therapy
  • Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study treatment administration, or New York Heart Association Class III or IV congestive heart failure
  • Has a known history of HIV infection
  • Has a known history of Hepatitis B or known active Hepatitis C virus infection
  • Has had major surgery <3 weeks before the first dose of study treatment
  • Is expected to require any other form of antineoplastic therapy while on study
  • Has received prior radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the first dose of study treatment
  • Has received a live vaccine within 30 days before the first dose of study treatment
  • Has received any prior immunotherapy and was discontinued from that treatment due to a severe or worse immune-related adverse event (irAE)
  • Has had chemotherapy or biological cancer therapy within 4 weeks before the first dose of study treatment or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from the AEs due to cancer therapeutics administered more than 4 weeks before the first dose of study treatment (including participants who had previous immunomodulatory therapy with residual irAEs)
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study treatment
  • Previously had a severe hypersensitivity reaction to treatment with monoclonal antibodies (including pembrolizumab) and/or any of their excipients
  • 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 after the last dose of study treatment
  • Has had an allogenic tissue/solid organ transplant

    *Substudy 1 Only:

  • Has symptomatic ascites or pleural effusion (if receiving pemetrexed)
  • Has a history or current evidence of a gastrointestinal (GI) condition (e.g. inflammatory bowel disease, Crohn's disease, ulcerative colitis) or impaired liver function or diseases that in the opinion of the investigator may significantly alter the absorption or metabolism of oral medications
  • Is getting chemotherapy and has clinically active diverticulitis, intra-abdominal abscess, GI obstruction, or peritoneal carcinomatosis
  • Has pre-existing neuropathy that is moderate in intensity
  • Is unable to interrupt aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs), other than aspirin dose less than or equal to 1.3 gm/day for a 5-day period (8-day period for long acting agents such as peroxicam), for participants who will receive pemetrexed
  • Is unable or unwilling to take folic acid or vitamin B12 supplementation, for participants who will receive pemetrexed
  • Has a known sensitivity to any component of carboplatin, paclitaxel, pemetrexed or any of their excipients

    *Substudies 1 and 2 Only:

  • Has received prior systemic cytotoxic chemotherapy or other targeted or biological antineoplastic therapy for metastatic disease
  • Has received prior therapy with an anti-programmed cell death-1 (PD-1), anti-programmed cell death-ligand 1 (PD-L1), or anti-PD-L2 agent or prior therapy targeting other immunoregulatory receptors or mechanisms

    *Substudy 3 Only:

  • Has received prior therapy targeting other immuno-regulatory receptors or mechanisms, not including anti-PD-(L)1 agents
  • Has participated in Substudies 1 or 2

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04165798


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
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Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT04165798    
Other Study ID Numbers: 3475-U01
MK-3475-U01 ( Other Identifier: Merck )
KEYMAKER-U01 ( Other Identifier: Merck )
First Posted: November 18, 2019    Key Record Dates
Last Update Posted: June 11, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme Corp.:
Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases