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A Study of MK-1084 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With KRASG12C Mutant Advanced Solid Tumors (MK-1084-001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05067283
Recruitment Status : Recruiting
First Posted : October 5, 2021
Last Update Posted : September 23, 2022
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Tracking Information
First Submitted Date  ICMJE October 1, 2021
First Posted Date  ICMJE October 5, 2021
Last Update Posted Date September 23, 2022
Actual Study Start Date  ICMJE December 17, 2021
Estimated Primary Completion Date February 4, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 16, 2022)
  • Number of participants who experienced a dose-limiting toxicity (DLT) [ Time Frame: Up to ~21 days ]
    A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0). Number of participants who experience a DLT will be reported.
  • Number of participants who experienced an adverse event (AE) [ Time Frame: Up to ~50 months ]
    An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experience an AE will be reported.
  • Number of participants who discontinued study treatment due to an AE [ Time Frame: Up to ~50 months ]
    An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who discontinue study treatment due to an AE will be reported.
Original Primary Outcome Measures  ICMJE
 (submitted: October 1, 2021)
  • Number of participants who experienced a dose-limiting toxicity (DLT) [ Time Frame: Up to ~21 days ]
    A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0). Number of participants who experience a DLT will be reported.
  • Number of participants who experienced an adverse event (AE) [ Time Frame: Up to ~50 months ]
    An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experienced an AE will be reported.
  • Number of participants who discontinued study treatment due to an AE [ Time Frame: Up to ~50 months ]
    An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who discontinued study treatment due to an AE will be reported.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 16, 2022)
  • Objective response rate (ORR) [ Time Frame: Up to ~50 months ]
    ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). The percentage of participants who experience a CR or PR as assessed by the investigator based on RECIST 1.1 will be reported.
  • Duration of response (DOR) [ Time Frame: Up to ~50 months ]
    DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 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 at least 5 mm. The appearance of one or more new lesions is also considered PD. The DOR as assessed by the investigator will be reported.
  • Maximum plasma concentration (Cmax) of MK-1084 [ Time Frame: Pre-dose and 1, 2, 4 and 8 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1; Pre-dose on Cycle 1 Day 2, Cycle 1 Day 15, Cycle 2 Day 2, Cycle 3 Day 1, Cycle 6 Day 1 and Day 1 of every third cycle (up to ~50 months). Each cycle = 21 days ]
    Cmax of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
  • Area under the plasma concentration-time curve (AUC) of MK-1084 [ Time Frame: Pre-dose and 1, 2, 4 and 8 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1; Pre-dose on Cycle 1 Day 2, Cycle 1 Day 15, Cycle 2 Day 2, Cycle 3 Day 1, Cycle 6 Day 1 and Day 1 of every third cycle (up to ~50 months). Each cycle = 21 days ]
    AUC of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 1, 2021)
  • Objective response rate (ORR) [ Time Frame: Up to ~50 months ]
    ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). The percentage of participants who experience a CR or PR as assessed by the investigator based on RECIST 1.1 will be reported.
  • Duration of response (DOR) [ Time Frame: Up to ~50 months ]
    DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. The DOR as assessed by the investigator will be reported.
  • Maximum plasma concentration (Cmax) of MK-1084 [ Time Frame: Pre-dose and 1, 2, 4 and 8 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1; Pre-dose on Cycle 1 Day 2, Cycle 1 Day 15, Cycle 2 Day 2, Cycle 3 Day 1, Cycle 6 Day 1 and Day 1 of every third cycle (up to ~50 months). Each cycle = 21 days ]
    Cmax of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
  • Area under the plasma concentration-time curve (AUC) of MK-1084 [ Time Frame: Pre-dose and 1, 2, 4 and 8 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1; Pre-dose on Cycle 1 Day 2, Cycle 1 Day 15, Cycle 2 Day 2, Cycle 3 Day 1, Cycle 6 Day 1 and Day 1 of every third cycle (up to ~50 months). Each cycle = 21 days ]
    AUC of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of MK-1084 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With KRASG12C Mutant Advanced Solid Tumors (MK-1084-001)
Official Title  ICMJE A Phase 1, Open-Label, Multicenter Study to Assess Safety, Tolerability, PK, and Efficacy of MK-1084 as Monotherapy and in Combination With Pembrolizumab in Subjects With KRASG12C Mutant Advanced Solid Tumors
Brief Summary This is a study evaluating the efficacy, safety, and pharmacokinetics of MK-1084 in participants with advanced solid tumors with identified kirsten rat sarcoma viral oncogene homolog G12C (KRASG12C) mutation and MK-1084 plus pembrolizumab in participants with first line (1L) non-small cell lung cancer (NSCLSC) with identified KRASG12C mutation.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE
  • Drug: MK-1084
    Oral dose of 25 or 50 mg tablets
  • Biological: Pembrolizumab
    Intravenous infusion of 200 mg
    Other Names:
    • KEYTRUDA®
    • MK-3475
Study Arms  ICMJE
  • Experimental: MK-1084
    Participants will receive MK-1084 daily oral escalating doses of 25 mg, 50 mg, 100 mg, 200 mg, 400 mg, and 800 mg until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety.
    Intervention: Drug: MK-1084
  • Experimental: Pembrolizumab plus MK-1084
    Participants will receive MK-1084 daily oral escalating dose of 25 mg, 50 mg, 100 mg, 200 mg, 400 mg, and 800 mg plus pembrolizumab given as a 200 mg intravenous infusion once every 21-day cycle up to a total of 35 cycles (up to ~24 months). Treatment with MK-1084 will continue until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety.
    Interventions:
    • Drug: MK-1084
    • Biological: Pembrolizumab
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 16, 2022)
264
Original Estimated Enrollment  ICMJE
 (submitted: October 1, 2021)
185
Estimated Study Completion Date  ICMJE February 4, 2026
Estimated Primary Completion Date February 4, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

For treatment with MK-1084 - Has locally advanced unresectable or metastatic solid-tumor malignancy with histologically OR blood-based confirmation of KRASG12C mutation who has received at least 1 line of therapy for systemic disease.

For treatment with pembrolizumab plus MK-1084

- Has an untreated metastatic NSCLC with histological OR blood-based confirmation of KRASG12C mutation and histologic confirmation of tumor proportion score (TPS) ≥1%.

For all participants:

  • Has measurable disease by RECIST 1.1 criteria.
  • Has adequate organ function.
  • Male participants must be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR must agree to use contraception unless confirmed to be azoospermic.
  • Female participants must not be pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of child-bearing potential (WOCBP); is a WOCBP and uses a contraceptive method that is highly effective, with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle and must have a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention.

Exclusion Criteria:

  • Has received chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation).
  • Has a history of second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 5 years.
  • Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Has an active infection requiring systemic therapy.
  • Has a history of human immunodeficiency virus (HIV) and/or hepatitis B or C infections.
  • Has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
  • Has a history of interstitial lung disease, noninfectious pneumonitis requiring active steroid therapy, or ongoing pneumonitis.
  • Has an active autoimmune disease requiring systemic therapy.
  • Has not fully recovered from any effects of major surgical procedure without significant detectable infection.
  • Has one or more of the following ophthalmological findings/conditions: intraocular pressure >21 mm Hg and/or any diagnosis of glaucoma; diagnosis of central serous retinopathy, retinal vein occlusion, or retinal artery occlusion and/or a diagnosis of retinal degenerative disease.
  • Has received live or live-attenuated vaccine within 4 weeks of study start.
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: Toll Free Number 1-888-577-8839 Trialsites@merck.com
Listed Location Countries  ICMJE Australia,   Canada,   Chile,   Israel,   Japan,   Korea, Republic of,   New Zealand,   Poland,   Spain,   Switzerland,   Turkey,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05067283
Other Study ID Numbers  ICMJE 1084-001
MK-1084-001 ( Other Identifier: Merck )
jRCT2041220034 ( Registry Identifier: jRCT )
2021-004024-15 ( 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
Current Responsible Party Merck Sharp & Dohme LLC
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Merck Sharp & Dohme LLC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme LLC
PRS Account Merck Sharp & Dohme LLC
Verification Date September 2022

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