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KEYMAKER-U01 Substudy 1: Efficacy and Safety Study of Pembrolizumab (MK-3475) Plus Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A)

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ClinicalTrials.gov Identifier: NCT04165070
Recruitment Status : Recruiting
First Posted : November 15, 2019
Last Update Posted : August 26, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) PLUS chemotherapy in combination with vibostolimab (MK-7684) or MK-5890 in treatment-naïve participants with advanced squamous or non-squamous NSCLC.

This study is one of three pembrolizumab substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).


Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Biological: Pembrolizumab Drug: Carboplatin Drug: Paclitaxel Drug: Pemetrexed Biological: Vibostolimab Drug: MK-5890 Phase 2

Detailed Description:
The master screening protocol is MK-3475-U01 (KEYMAKER-U01) - NCT04165798

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: KEYMAKER-U01 Substudy 1: A Phase 2, Umbrella Study With Rolling Arms of Investigational Agents With Pembrolizumab in Combination With Chemotherapy in Treatment-Naive 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


Arm Intervention/treatment
Experimental: Pembrolizumab + Vibostolimab + Carboplatin + Paclitaxel
On Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg intravenously (IV) PLUS vibostolimab IV PLUS carboplatin Area Under the Concentration-Time Curve (AUC) 6 IV PLUS paclitaxel 200 mg/m^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS vibostolimab IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®

Drug: Carboplatin
IV infusion
Other Name: PARAPLATIN®

Drug: Paclitaxel
IV infusion
Other Name: ABRAXANE®

Biological: Vibostolimab
IV infusion
Other Name: MK-7684

Experimental: Pembrolizumab + Vibostolimab + Carboplatin + Pemetrexed
On Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS vibostolimab IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS vibostolimab IV PLUS pemetrexed 500 mg/m^2 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®

Drug: Carboplatin
IV infusion
Other Name: PARAPLATIN®

Drug: Pemetrexed
IV infusion
Other Name: ALIMTA®

Biological: Vibostolimab
IV infusion
Other Name: MK-7684

Experimental: Pembrolizumab + MK-5890 + Carboplatin + Paclitaxel
On Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg intravenously (IV) PLUS carboplatin Area Under the Concentration-Time Curve (AUC) 6 IV PLUS paclitaxel 200 mg/m^2 IV PLUS MK-5890 IV on Day 1 every 6 weeks (every other 3-week cycle) (Q6W) in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV Q3W PLUS MK-5890 IV Q6W from Cycles 5 up to Cycle 35 (total treatment duration: up to approximately 2 years).
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®

Drug: Carboplatin
IV infusion
Other Name: PARAPLATIN®

Drug: Paclitaxel
IV infusion
Other Name: ABRAXANE®

Drug: MK-5890
IV infusion

Experimental: Pembrolizumab + MK-5890 + Carboplatin + Pemetrexed
On Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m^2 IV PLUS MK-5890 IV on Day 1 every 6 weeks (every other 3-week cycle) (Q6W) in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV Q3W PLUS pemetrexed 500 mg/m^2 IV Q3W PLUS MK-5890 IV Q6W from Cycles 5 up to Cycle 35 (total treatment duration: up to approximately 2 years).
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®

Drug: Carboplatin
IV infusion
Other Name: PARAPLATIN®

Drug: Pemetrexed
IV infusion
Other Name: ALIMTA®

Drug: MK-5890
IV infusion




Primary Outcome Measures :
  1. Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to approximately 24 months ]
    ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1.


Secondary Outcome Measures :
  1. Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to approximately 24 months ]
    PFS is defined as the time from first dose of study treatment until either the earliest date of documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD.

  2. Number of Participants Who Experience One or More Adverse Events (AEs) [ Time Frame: Up to approximately 27 months ]
    An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.

  3. Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) [ Time Frame: Up to approximately 24 months ]
    An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.



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
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 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 for at least 120 days after the last dose of pembrolizumab and for at least 180 days after the last dose of chemotherapy
  • Female participants must not be pregnant or breastfeeding, and at least one 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 for at least 120 days after the last dose of pembrolizumab and for at least 180 days after the last dose of 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 that required steroids or has current pneumonitis
  • 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 symptomatic ascites or pleural effusion (if receiving pemetrexed; Alimta®, Eli Lilly)
  • 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
  • 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
  • Is currently receiving either strong or moderate inhibitors of cytochrome P450 3A4 (CYP3A4) or cytochrome P450 2C8 (CYP2C8) that cannot be discontinued for the duration of the study
  • Is currently receiving strong or moderate inducers of CYP3A4 or CYP2C8 that cannot be discontinued for the duration of the study
  • 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
  • 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

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): NCT04165070


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

Locations
Show Show 29 study locations
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: NCT04165070    
Other Study ID Numbers: 3475-01A
MK-3475-01A ( Other Identifier: Merck )
KEYMAKER-U01A ( Other Identifier: Merck )
2020-001626-56 ( EudraCT Number )
First Posted: November 15, 2019    Key Record Dates
Last Update Posted: August 26, 2021
Last Verified: August 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
Paclitaxel
Carboplatin
Pembrolizumab
Pemetrexed
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors