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)
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|ClinicalTrials.gov Identifier: NCT05067283|
Recruitment Status : Recruiting
First Posted : October 5, 2021
Last Update Posted : March 30, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Advanced Solid Tumors||Drug: MK-1084 Biological: Pembrolizumab||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||264 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||December 17, 2021|
|Estimated Primary Completion Date :||February 4, 2026|
|Estimated Study Completion Date :||February 4, 2026|
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.
Oral dose of 25 or 50 mg tablets
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.
Oral dose of 25 or 50 mg tablets
Intravenous infusion of 200 mg
- 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.
- 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.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
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.
- 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.
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): NCT05067283
|Contact: Toll Free Number||1-888-577-8839||Trialsites@merck.com|
|Study Director:||Medical Director||Merck Sharp & Dohme LLC|
|Responsible Party:||Merck Sharp & Dohme LLC|
|Other Study ID Numbers:||
MK-1084-001 ( Other Identifier: Merck )
jRCT2041220034 ( Registry Identifier: jRCT )
2021-004024-15 ( EudraCT Number )
|First Posted:||October 5, 2021 Key Record Dates|
|Last Update Posted:||March 30, 2023|
|Last Verified:||March 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Antineoplastic Agents, Immunological