A Study of MK-1084 in KRAS Mutant Advanced Solid Tumors (MK-1084-001)

Advanced Solid Tumors Clinical Trial

Official title:

A Phase 1, Open-label, Multicenter Study to Assess Safety, Tolerability, PK, and Efficacy of MK-1084 as Monotherapy and as Part of Various Combination Therapies in Participants With KRAS G12C Mutant Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05067283
• Other study ID #: 1084-001
• Secondary ID: MK-1084-001jRCT2
• Status: Recruiting
• Phase: Phase 1
• Start date: December 17, 2021
• Est. completion date: August 19, 2026

Study information

• Verified date: June 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 830
• Est. completion date: August 19, 2026
• Est. primary completion date: August 19, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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: 3L/4L metastatic colorectal cancer (mCRC)

• Has histologically or cytologically confirmed diagnosis of unresectable and metastatic colorectal adenocarcinoma with histological or blood-based confirmation of KRAS G12C mutation

• Previous treatment failure of 2 or 3 previous lines 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• MK-1084
Oral dose

Biological:
• Pembrolizumab
Intravenous infusion of 200 mg

Drug:
• carboplatin
Per label
• pemetrexed
Per label

Biological:
• cetuximab
Per label

Drug:
• oxaliplatin
Per label
• leucovorin
Per label
• 5-fluorouracil
Per label

Locations

Country	Name	City	State
Australia	Chris O'Brien Lifehouse ( Site 0002)	Camperdown	New South Wales
Australia	Monash Health-Oncology Research ( Site 0003)	Clayton	Victoria
Australia	Liverpool Hospital-Medical Oncology ( Site 0001)	Liverpool	New South Wales
Australia	Westmead Hospital-Department of Medical Oncology ( Site 0006)	Westmead	New South Wales
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	The Moncton Hospital ( Site 0037)	Moncton	New Brunswick
Canada	Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0032)	Toronto	Ontario
Chile	Bradfordhill ( Site 0042)	Santiago	Region M. De Santiago
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	James Lind Centro de Investigación del Cáncer ( Site 0043)	Temuco	Araucania
China	Beijing Friendship Hospital Affiliate of Capital University-Oncology ( Site 0417)	Beijing	Beijing
China	Jilin Cancer Hospital-oncology department ( Site 0412)	Changchun	Jilin
China	Fujian Cancer Hospital ( Site 0419)	Fuzhou	Fujian
China	Southern Medical University Nanfang Hospital-Depatrment of Respiratory and Critical Care Medicine (	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center-Internal medicine ( Site 0415)	Guangzhou	Guangdong
China	Zhejiang Cancer Hospital-Thoracic oncology ( Site 0411)	Hangzhou	Zhejiang
China	Shanghai Chest Hospital-Oncology department ( Site 0410)	Shanghai	Shanghai
China	Shanghai East Hospital ( Site 0416)	Shanghai	Shanghai
China	Wuhan Union Hospital Cancer Center-Cancer Center ( Site 0418)	Wuhan	Hubei
Denmark	Odense Universitetshospital-Department of oncology ( Site 0421)	Odense	Syddanmark
Israel	Rambam Health Care Campus-Oncology ( Site 0090)	Haifa
Israel	Hadassah Medical Center-Oncology ( Site 0094)	Jerusalem
Israel	Shaare Zedek Medical Center-Oncology ( Site 0092)	Jerusalem
Israel	Meir Medical Center ( Site 0091)	Kfar Saba
Israel	Sheba Medical Center-ONCOLOGY ( Site 0093)	Ramat Gan
Japan	National Cancer Center Hospital ( Site 0403)	Chuo-ku	Tokyo
Japan	National Cancer Center Hospital East ( Site 0404)	Kashiwa	Chiba
Japan	Japanese Foundation for Cancer Research ( Site 0400)	Koto	Tokyo
Japan	Shizuoka Cancer Center ( Site 0401)	Nagaizumi	Shizuoka
Japan	Kanagawa cancer center ( Site 0402)	Yokohama	Kanagawa
Korea, Republic of	Samsung Medical Center-Division of Hematology/Oncology ( Site 0193)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 0191)	Seoul
New Zealand	New Zealand Clinical Research (Christchurch) ( Site 0004)	Christchurch	Canterbury
Panama	Centro Hemato Oncológico Paitilla ( Site 0163)	Panama City
Panama	Centro Oncologico de Panama ( Site 0160)	Panama City
Poland	Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0171)	Gdansk	Pomorskie
Poland	Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0173)	Koszalin	Zachodniopomorskie
Poland	Uniwersytecki Szpital Kliniczny w Poznaniu ( Site 0172)	Poznan	Wielkopolskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 0170	Warszawa	Mazowieckie
Spain	Hospital Universitari Vall d'Hebron-Oncology ( Site 0212)	Barcelona
Spain	Clinica Universidad de Navarra ( Site 0213)	Madrid	Madrid, Comunidad De
Spain	Hospital Universitario Fundación Jiménez Díaz-START Madrid-FJD ( Site 0211)	Madrid	Madrid, Comunidad De
Switzerland	Ospedale Regionale Bellinzona e Valli ( Site 0220)	Bellinzona	Ticino
Switzerland	Cantonal Hospital St.Gallen ( Site 0224)	St.Gallen	Sankt Gallen
Taiwan	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
Turkey	Hacettepe Universite Hastaneleri-oncology hospital ( Site 0234)	Ankara
Turkey	Ege University Medicine of Faculty ( Site 0231)	Bornova	Izmir
Turkey	Erciyes University ( Site 0232)	Talas	Kayseri
Turkey	Ankara City Hospital-oncology ( Site 0233)	Yenimahalle	Ankara
United States	NEXT Virginia ( Site 0271)	Fairfax	Virginia
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	MEDICAL COLLEGE OF WISCONSIN-Cancer Center Clinical Trials Office ( Site 0262)	Milwaukee	Wisconsin
United States	Laura and Isaac Perlmutter Cancer Center ( Site 0270)	New York	New York
United States	Moffitt Cancer Center ( Site 0261)	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Chile,  China,  Denmark,  Israel,  Japan,  Korea, Republic of,  New Zealand,  Panama,  Poland,  Spain,  Switzerland,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Experience a Dose-Limiting Toxicity (DLT)	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.	Up to ~21 days
Primary	Number of Participants Who Experience an Adverse Event (AE)	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.	Up to ~56 months
Primary	Number of Participants Who Discontinue Study Treatment Due to an AE	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.	Up to ~56 months
Secondary	Objective Response Rate (ORR)	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.	Up to ~56 months
Secondary	Duration of Response (DOR)	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.	Up to ~56 months
Secondary	Mean Plasma Concentration of MK-1084	Mean Plasma Concentration of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.	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)
Secondary	Maximum Concentration (Cmax) of MK-1084	Cmax of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.	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).
Secondary	Time to Maximum Concentration (Tmax) of MK-1084	Tmax of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.	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)
Secondary	Minimum Concentration (Cmin) of MK-1084	Cmin of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.	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)
Secondary	Area Under the Concentration Time-Curve 0-12 Hours (AUC 0-12) of MK-1084	AUC 0-12 of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.	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)
Secondary	Area Under the Concentration Time-Curve 0-24 Hours (AUC 0-24) of MK-1084	AUC 0-24 of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.	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)
Secondary	Half-Life (t1/2) of MK-1084	Half-Life (t1/2) of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.	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)

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary