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KEYMAKER-U01 Substudy 3: Efficacy and Safety Study of Pembrolizumab (MK-3475) When Used With Investigational Agents in Participants With Advanced Non-small Cell Lung Cancer (NSCLC), Previously Treated With Anti-programmed Cell Death Receptor Ligand 1 (PD-L1) Therapy (MK-3475-01C/KEYMAKER-U01C)

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ClinicalTrials.gov Identifier: NCT04165096
Recruitment Status : Active, not recruiting
First Posted : November 15, 2019
Last Update Posted : June 15, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE November 14, 2019
First Posted Date  ICMJE November 15, 2019
Last Update Posted Date June 15, 2021
Actual Study Start Date  ICMJE January 21, 2020
Estimated Primary Completion Date February 13, 2032   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 14, 2019)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 2, 2021)
  • 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.
  • 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.
  • Number of Participants Who Discontinued 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 14, 2019)
  • 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 to the first 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.
  • 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.
  • Number of Participants Who Discontinued 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE KEYMAKER-U01 Substudy 3: Efficacy and Safety Study of Pembrolizumab (MK-3475) When Used With Investigational Agents in Participants With Advanced Non-small Cell Lung Cancer (NSCLC), Previously Treated With Anti-programmed Cell Death Receptor Ligand 1 (PD-L1) Therapy (MK-3475-01C/KEYMAKER-U01C)
Official Title  ICMJE 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
Brief Summary

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) in combination with MK-5890 or MK-4830 in participants with advanced squamous or non-squamous NSCLC that have been previously treated with anti-PD-L1 therapy.

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

Enrollment in the pembrolizumab+MK-5890 arm has been completed with Amendment 4.

Detailed Description The master screening protocol is MK-3475-U01 (KEYMAKER-U01) - NCT04165798
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Non-Small-Cell Lung
Intervention  ICMJE
  • Biological: Pembrolizumab
    IV infusion
    Other Names:
    • KEYTRUDA®
    • MK-3475
    • SCH 900475
  • Biological: MK-5890
    IV infusion
  • Biological: MK-4830
    IV infusion
  • Drug: diphenhydramine
    PO
  • Drug: acetaminophen
    PO
  • Biological: MK-0482
    IV infusion
Study Arms  ICMJE
  • Experimental: Pembrolizumab + MK-5890
    On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS MK-5890 IV for a maximum of 35 cycles (approximately 2 years). All participants are premedicated 1.5 hours (±30 minutes) before infusion of MK-5890 with 50 mg oral (PO) diphenhydramine (or equivalent dose of antihistamine) and 500-1000 mg of acetaminophen PO (or equivalent dose of analgesic).
    Interventions:
    • Biological: Pembrolizumab
    • Biological: MK-5890
    • Drug: diphenhydramine
    • Drug: acetaminophen
  • Experimental: Pembrolizumab + MK-4830
    On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS MK-4830 IV for a maximum of 35 cycles (approximately 2 years).
    Interventions:
    • Biological: Pembrolizumab
    • Biological: MK-4830
  • Experimental: Pembrolizumab + MK-0482
    On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS MK-0482 IV for a maximum of 35 cycles (approximately 2 years).
    Interventions:
    • Biological: Pembrolizumab
    • Biological: MK-0482
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: June 10, 2021)
135
Original Estimated Enrollment  ICMJE
 (submitted: November 14, 2019)
45
Estimated Study Completion Date  ICMJE February 13, 2032
Estimated Primary Completion Date February 13, 2032   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion:

  • Has a histologically- or cytologically-confirmed diagnosis of Stage IV squamous or non-squamous NSCLC
  • Has non-squamous NSCLC and is 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
  • Have 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
  • Have progressive disease (PD) during/after platinum doublet chemotherapy
  • Is able to complete all screening procedures within the 35-day screening window
  • Male participants must agree to use contraception and refrain from donating sperm during the treatment period and for at least 120 days after the last dose of study treatment
  • 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 study treatment
  • Has adequate organ function within 10 days of initiation of study treatment

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, or New York Heart Association Class III or IV congestive heart failure
  • Has a known history of Human Immunodeficiency Virus (HIV) infection
  • Has a known history of Hepatitis B or known active Hepatitis C virus infection
  • Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study
  • Has had major surgery <3 weeks before the first dose of study treatment
  • 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
  • Has participated in Substudies 1 or 2
  • Has 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Hungary,   Israel,   Korea, Republic of,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04165096
Other Study ID Numbers  ICMJE 3475-01C
MK-3475-01C ( Other Identifier: Merck )
KEYMAKER-U01C ( Other Identifier: Merck )
2020-001629-29 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP