A Study of MK-1084 in KRAS Mutant Advanced Solid Tumors (MK-1084-001)
- Conditions
- Advanced Solid Tumors
- Interventions
- Registration Number
- NCT05067283
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
This is a study evaluating the safety, pharmacokinetics, and efficacy of MK-1084 alone, and MK-1084 plus other combination therapies in participants with advanced solid tumors with identified kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 830
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 (for a urine test) or 72 hours (for a serum test) before the first dose of study intervention
For Arm 1 - Has locally advanced unresectable or metastatic solid-tumor malignancy with histologically OR blood-based confirmation of KRAS G12C mutation who has received at least 1 line of therapy for systemic disease
For Arm 2
- Has an untreated metastatic non-small cell lung cancer (NSCLC) with histologically OR blood-based confirmation of KRAS G12C mutation and histologic confirmation of programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥1%
For Arm 3
- Has locally advanced unresectable or metastatic solid-tumor malignancy with histologically or blood-based confirmation of KRAS G12C mutation who has received at least 1 line of therapy for systemic disease Expansion Group A: 2L+NSCLC
- Has histologically or cytologically confirmed diagnosis of unresectable or metastatic NSCLC with histological or blood-based confirmation of KRAS G12C mutation
- Previous treatment failure of at least 1 line of systemic therapy Expansion Group B
- Has locally advanced unresectable or metastatic solid-tumor malignancy, excluding NSCLC or CRC, with histologically or blood- based confirmation of KRAS G12C mutation who has received at least 1 line of therapy for systemic disease
Arm 4 only - Has an untreated advanced or metastatic nonsquamous NSCLC with histologically or blood-based confirmation of KRAS G12C mutation
Arm 5 only
- Histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic colorectal adenocarcinoma and with histologically or blood-based confirmation of KRAS G12C mutation
- Previous treatment failure of one or 2 previous line(s) of systemic therapy
Arm 6 only
- Locally advanced unresectable or metastatic colorectal adenocarcinoma with histologically or blood-based confirmation of KRAS G12C mutation
- Has received chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) before first dose of study intervention
- 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
- Known history of HIV infection or. has a known history of Hepatitis B virus or known active Hepatitis C virus infection
- 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
Arm 4 Only
- Is unable to interrupt aspirin or other nonsteroidal anti-inflammatories (NSAIDs), other than an aspirin dose ≤1.3 grams per day, for at least 2 days (5 days for long-acting agents [for example, piroxicam]) before, during, and for at least 2 days after administration of pemetrexed.
- Is unable/unwilling to take folic acid, vitamin B12, and dexamethasone
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 4 Pembrolizumab Participants will receive MK-1084 daily oral dose plus an intravenous infusion of pembrolizumab (200 mg) once every 21-day cycle for up to 35 cycles (up to \~24 months). Participants will also receive carboplatin (per label) and pemetrexed (per label) once every 21-day cycle for the first 4 cycles. Arm 3 MK-1084 Participants will receive alternate formulation of MK-1084 until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety. Arm 5 MK-1084 Participants will receive MK-1084 daily oral dose plus an intravenous infusion of cetuximab (per label) every 2 weeks of each 28-day cycle. Arm 6 oxaliplatin Participants will receive MK-1084 daily oral dose. Additionally, participants receive an intravenous infusion of cetuximab (per label) every 2 weeks of each 28-day cycle, oxaliplatin (per label) for first 6 cycles, and leucovorin (per label) and 5-fluorouracil (per label) once every 14-days. Arm 1 MK-1084 Participants will receive daily oral escalating doses of up to 800 mg of MK-1084 until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety. Arm 6 MK-1084 Participants will receive MK-1084 daily oral dose. Additionally, participants receive an intravenous infusion of cetuximab (per label) every 2 weeks of each 28-day cycle, oxaliplatin (per label) for first 6 cycles, and leucovorin (per label) and 5-fluorouracil (per label) once every 14-days. Arm 4 carboplatin Participants will receive MK-1084 daily oral dose plus an intravenous infusion of pembrolizumab (200 mg) once every 21-day cycle for up to 35 cycles (up to \~24 months). Participants will also receive carboplatin (per label) and pemetrexed (per label) once every 21-day cycle for the first 4 cycles. Arm 6 leucovorin Participants will receive MK-1084 daily oral dose. Additionally, participants receive an intravenous infusion of cetuximab (per label) every 2 weeks of each 28-day cycle, oxaliplatin (per label) for first 6 cycles, and leucovorin (per label) and 5-fluorouracil (per label) once every 14-days. Arm 2 MK-1084 Participants will receive MK-1084 daily oral escalating dose of up to 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. Arm 4 MK-1084 Participants will receive MK-1084 daily oral dose plus an intravenous infusion of pembrolizumab (200 mg) once every 21-day cycle for up to 35 cycles (up to \~24 months). Participants will also receive carboplatin (per label) and pemetrexed (per label) once every 21-day cycle for the first 4 cycles. Arm 2 Pembrolizumab Participants will receive MK-1084 daily oral escalating dose of up to 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. Arm 4 pemetrexed Participants will receive MK-1084 daily oral dose plus an intravenous infusion of pembrolizumab (200 mg) once every 21-day cycle for up to 35 cycles (up to \~24 months). Participants will also receive carboplatin (per label) and pemetrexed (per label) once every 21-day cycle for the first 4 cycles. Arm 5 cetuximab Participants will receive MK-1084 daily oral dose plus an intravenous infusion of cetuximab (per label) every 2 weeks of each 28-day cycle. Arm 6 cetuximab Participants will receive MK-1084 daily oral dose. Additionally, participants receive an intravenous infusion of cetuximab (per label) every 2 weeks of each 28-day cycle, oxaliplatin (per label) for first 6 cycles, and leucovorin (per label) and 5-fluorouracil (per label) once every 14-days. Arm 6 5-fluorouracil Participants will receive MK-1084 daily oral dose. Additionally, participants receive an intravenous infusion of cetuximab (per label) every 2 weeks of each 28-day cycle, oxaliplatin (per label) for first 6 cycles, and leucovorin (per label) and 5-fluorouracil (per label) once every 14-days.
- Primary Outcome Measures
Name Time Method Number of Participants Who Discontinue Study Treatment Due to an AE Up to ~56 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.
Number of Participants Who Experience an Adverse Event (AE) Up to ~56 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 Experience a Dose-Limiting Toxicity (DLT) 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.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) Up to ~56 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) Up to ~56 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.
Time to Maximum Concentration (Tmax) of MK-1084 At designated timepoints during the study in Cycles 1, 2, 3, 5, 9, 13, 17, 21, 25, and every 6 weeks thereafter up to 56 months. Cycle=3 weeks (Arms 1-4) and 4 weeks (Arms 5-6) Tmax of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Minimum Concentration (Cmin) of MK-1084 At designated timepoints during the study in Cycles 1, 2, 3, 5, 9, 13, 17, 21, 25, and every 6 weeks thereafter up to 56 months. Cycle=3 weeks (Arms 1-4) and 4 weeks (Arms 5-6) Cmin of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Area Under the Concentration Time-Curve 0-12 Hours (AUC 0-12) of MK-1084 At designated timepoint during the study in Cycle 1 Day 1: Predose and up to 12 hours postdose. Cycle=3 weeks (Arms 1-4) and 4 weeks (Arms 5-6) AUC 0-12 of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Area Under the Concentration Time-Curve 0-24 Hours (AUC 0-24) of MK-1084 At designated timepoint during the study in Cycle 1 Day 1: Predose and up to 24 hours postdose. Cycle=3 weeks (Arms 1-4) and 4 weeks (Arms 5-6) AUC 0-24 of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Half-Life (t1/2) of MK-1084 At designated timepoint during the study in Cycle 1 Day 1: Predose and up to 24 hours postdose. Cycle=3 weeks (Arms 1-4) and 4 weeks (Arms 5-6) Half-Life (t1/2) of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Mean Plasma Concentration of MK-1084 At designated timepoints during the study in Cycles 1, 2, 3, 5, 9, 13, 17, 21, 25, and every 6 weeks thereafter up to 56 months. Cycle=3 weeks (Arms 1-4) and 4 weeks (Arms 5-6) Mean Plasma Concentration of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Maximum Concentration (Cmax) of MK-1084 At designated timepoints during the study in Cycles 1, 2, 3, 5, 9, 13, 17, 21, 25, and every 6 weeks thereafter up to 56 months. Cycle=3 weeks (Arms 1-4) and 4 weeks (Arms 5-6). Cmax of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Trial Locations
- Locations (68)
Moffitt Cancer Center ( Site 0261)
🇺🇸Tampa, Florida, United States
START Midwest ( Site 0267)
🇺🇸Grand Rapids, Michigan, United States
John Theurer Cancer Center at Hackensack University Medical Center ( Site 0260)
🇺🇸Hackensack, New Jersey, United States
Laura and Isaac Perlmutter Cancer Center ( Site 0270)
🇺🇸New York, New York, United States
NEXT Virginia ( Site 0271)
🇺🇸Fairfax, Virginia, United States
MEDICAL COLLEGE OF WISCONSIN-Cancer Center Clinical Trials Office ( Site 0262)
🇺🇸Milwaukee, Wisconsin, United States
Chris O'Brien Lifehouse ( Site 0002)
🇦🇺Camperdown, New South Wales, Australia
Liverpool Hospital-Medical Oncology ( Site 0001)
🇦🇺Liverpool, New South Wales, Australia
Westmead Hospital ( Site 0006)
🇦🇺Westmead, New South Wales, Australia
Monash Health-Oncology Research ( Site 0003)
🇦🇺Clayton, Victoria, Australia
Cross Cancer Institute ( Site 0033)
🇨🇦Edmonton, Alberta, Canada
The Moncton Hospital ( Site 0037)
🇨🇦Moncton, New Brunswick, Canada
Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0030)
🇨🇦Hamilton, Ontario, Canada
Kingston Health Sciences Centre-Kingston General Hospital Site ( Site 0036)
🇨🇦Kingston, Ontario, Canada
Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0032)
🇨🇦Toronto, Ontario, Canada
James Lind Centro de Investigacion del Cancer ( Site 0043)
🇨🇱Temuco, Araucania, Chile
Centro de Estudios Clínicos SAGA-CECSAGA ( Site 0041)
🇨🇱Santiago, Region M. De Santiago, Chile
FALP-UIDO ( Site 0040)
🇨🇱Santiago, Region M. De Santiago, Chile
Bradfordhill ( Site 0042)
🇨🇱Santiago, Region M. De Santiago, Chile
Beijing Friendship Hospital Affiliate of Capital University-Oncology ( Site 0417)
🇨🇳Beijing, Beijing, China
Fujian Cancer Hospital ( Site 0419)
🇨🇳Fuzhou, Fujian, China
Southern Medical University Nanfang Hospital-Depatrment of Respiratory and Critical Care Medicine ( Site 0413)
🇨🇳Guangzhou, Guangdong, China
Sun Yat-sen University Cancer Center-Internal medicine ( Site 0415)
🇨🇳Guangzhou, Guangdong, China
Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 0418)
🇨🇳Wuhan, Hubei, China
Jilin Cancer Hospital-oncology department ( Site 0412)
🇨🇳Changchun, Jilin, China
Shanghai Chest Hospital-Oncology department ( Site 0410)
🇨🇳Shanghai, Shanghai, China
Shanghai East Hospital ( Site 0416)
🇨🇳Shanghai, Shanghai, China
Zhejiang Cancer Hospital-Thoracic oncology ( Site 0411)
🇨🇳Hangzhou, Zhejiang, China
Odense Universitetshospital-Department of oncology ( Site 0421)
🇩🇰Odense, Syddanmark, Denmark
Rambam Health Care Campus-Oncology ( Site 0090)
🇮🇱Haifa, Israel
Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0171)
🇵🇱Gdansk, Pomorskie, Poland
Uniwersytecki Szpital Kliniczny w Poznaniu ( Site 0172)
🇵🇱Poznan, Wielkopolskie, Poland
Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0173)
🇵🇱Koszalin, Zachodniopomorskie, Poland
Clinica Universidad de Navarra ( Site 0213)
🇪🇸Madrid, Madrid, Comunidad De, Spain
Shaare Zedek Medical Center-Oncology ( Site 0092)
🇮🇱Jerusalem, Israel
Hadassah Medical Center-Oncology ( Site 0094)
🇮🇱Jerusalem, Israel
Meir Medical Center. ( Site 0091)
🇮🇱Kfar Saba, Israel
Sheba Medical Center-ONCOLOGY ( Site 0093)
🇮🇱Ramat Gan, Israel
Humanitas ( Site 0113)
🇮🇹Rozzano, Lombardia, Italy
ospedale le scotte-U.O.C. Immunoterapia Oncologica ( Site 0111)
🇮🇹Siena, Toscana, Italy
Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0110)
🇮🇹Napoli, Italy
National Cancer Center Hospital East ( Site 0404)
🇯🇵Kashiwa, Chiba, Japan
Kanagawa Cancer Center ( Site 0402)
🇯🇵Yokohama, Kanagawa, Japan
Shizuoka Cancer Center ( Site 0401)
🇯🇵Nagaizumi, Shizuoka, Japan
National Cancer Center Hospital ( Site 0403)
🇯🇵Chuo-ku, Tokyo, Japan
Cancer Institute Hospital of JFCR ( Site 0400)
🇯🇵Koto, Tokyo, Japan
Seoul National University Hospital ( Site 0191)
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center-Division of Hematology/Oncology ( Site 0193)
🇰🇷Seoul, Korea, Republic of
New Zealand Clinical Research (Christchurch) ( Site 0004)
🇳🇿Christchurch, Canterbury, New Zealand
Centro Oncologico de Panama ( Site 0160)
🇵🇦Panama City, Panama
Centro Hemato Oncológico Paitilla ( Site 0163)
🇵🇦Panama City, Panama
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 0170)
🇵🇱Warszawa, Mazowieckie, Poland
Hospital Universitario Fundación Jiménez Díaz-START Madrid-FJD ( Site 0211)
🇪🇸Madrid, Madrid, Comunidad De, Spain
Hospital Universitari Vall d'Hebron-Oncology ( Site 0212)
🇪🇸Barcelona, Spain
Cantonal Hospital St.Gallen ( Site 0224)
🇨🇭St.Gallen, Sankt Gallen, Switzerland
Ospedale Regionale Bellinzona e Valli ( Site 0220)
🇨🇭Bellinzona, Ticino, Switzerland
Chang Gung Memorial Hospital at Kaohsiung-Oncology and Hematology ( Site 0445)
🇨🇳Kaohsiung Niao Sung Dist, Kaohsiung, Taiwan
National Cheng Kung University Hospital ( Site 0444)
🇨🇳Tainan, Taiwan
National Taiwan University Hospital-Oncology ( Site 0443)
🇨🇳Taipei, Taiwan
Ege University Medicine of Faculty ( Site 0231)
🇹🇷Bornova, Izmir, Turkey
Erciyes University ( Site 0232)
🇹🇷Talas, Kayseri, Turkey
Hacettepe Universite Hastaneleri-oncology hospital ( Site 0234)
🇹🇷Ankara, Turkey
Ankara City Hospital-oncology ( Site 0233)
🇹🇷Ankara, Turkey
MNPE ClinCenter of Oncology,Hematology,Transplantology and Palliative Care of CherkasyRegCouncil ( Site 0254)
🇺🇦Cherkasy, Cherkaska Oblast, Ukraine
Communal Non-Commercial Enterprise Prykarpatski Clinical Onc-Chemotherapy department ( Site 0251)
🇺🇦Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine
Private Enterprise Private Manufacturing Company Acinus-Medical and Diagnostic Centre ( Site 0255)
🇺🇦Kropyvnytskyi, Kirovohradska Oblast, Ukraine
Rivne Regional Clinical Hospital ( Site 0257)
🇺🇦Rivne, Rivnenska Oblast, Ukraine
Uzhhorod Multispecialty City Clinical Hospital ( Site 0258)
🇺🇦Uzhhorod, Zakarpatska Oblast, Ukraine