NCT05067283Recruiting
A Study of Calderasib (MK-1084) in KRAS Mutant Advanced Solid Tumors (MK-1084-001)
Summary
This is a study evaluating the safety, pharmacokinetics, and efficacy of calderasib alone, and calderasib plus other combination therapies in participants with advanced solid tumors with identified kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation.
Inclusion criteria
For all participants: • Has measurable disease by RECIST 1.1 criteria • Has adequate organ function • Male participants agree to protocol-specified contraception requirements including refraining from donating sperm and using protocol-specified contraceptives unless confirmed to be azoospermic • Female participants must not be pregnant or breastfeeding, and must agree to protocol-specified contraceptive requirements 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 histological 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 and submits archival tumor sample • 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
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 excluding age-related macular degeneration • 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
Contacts
The trial team's contact details are shown on request.
See the official trial record- Status
- Recruiting
- Phase
- Phase 1
- Study type
- Interventional
- Countries
- Switzerland, Italy, United States, Argentina, Australia, Canada, Chile, China, Denmark, Israel, Japan, Lithuania, Malaysia, New Zealand, Panama, Poland, South Korea, Spain, Taiwan, Turkey (Türkiye), Ukraine
- Sponsor
- Merck Sharp & Dohme LLC(Industry)
- Protocol no.
- 1084-001
- Conditions
- Advanced Solid Tumors
- Interventions
- Drug, Biological
Treatments studied
- Calderasib
- Pembrolizumab
- carboplatin
- pemetrexed
- cetuximab
- oxaliplatin
- leucovorin
- 5-fluorouracil
Locations · 67
- Sankt Gallen, SwitzerlandCantonal Hospital St.Gallen ( Site 0224)Recruiting at this site
- Bellinzona, SwitzerlandOspedale Regionale Bellinzona e Valli ( Site 0220)Recruiting at this site
- Rozzano, ItalyHumanitas ( Site 0113)Recruiting at this site
- Siena, Italyospedale le scotte-U.O.C. Immunoterapia Oncologica ( Site 0111)Recruiting at this site
- Naples, ItalyIstituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0110)Recruiting at this site
- Tampa, United StatesMoffitt Cancer Center ( Site 0261)Recruiting at this site
- Grand Rapids, United StatesSTART Midwest ( Site 0267)Recruiting at this site
- Hackensack, United StatesJohn Theurer Cancer Center at Hackensack University Medical Center ( Site 0260)Recruiting at this site
- Fairfax, United StatesNEXT Virginia ( Site 0271)Recruiting at this site
- Milwaukee, United StatesMEDICAL COLLEGE OF WISCONSIN-Cancer Center Clinical Trials Office ( Site 0262)Recruiting at this site
- Ciudad Autónoma de Buenos Aires, ArgentinaInstituto Alexander Fleming ( Site 0434)Recruiting at this site
- Rosario, ArgentinaSanatorio Parque ( Site 0456)Recruiting at this site
- La Rioja, ArgentinaFundación CORI para la Investigación y Prevención del Cáncer ( Site 0438)Recruiting at this site
- Camperdown, AustraliaChris O'Brien Lifehouse ( Site 0002)Recruiting at this site
- Liverpool, AustraliaLiverpool Hospital-Medical Oncology ( Site 0001)Recruiting at this site
- Westmead, AustraliaWestmead Hospital ( Site 0006)Recruiting at this site
- Clayton, AustraliaMonash Health-Oncology Research ( Site 0003)Recruiting at this site
- Edmonton, CanadaCross Cancer Institute ( Site 0033)Recruiting at this site
- Moncton, CanadaThe Moncton Hospital ( Site 0037)Recruiting at this site
- Hamilton, CanadaHamilton Health Sciences-Juravinski Cancer Centre ( Site 0030)Recruiting at this site
- Kingston, CanadaKingston Health Sciences Centre-Kingston General Hospital Site ( Site 0036)Recruiting at this site
- Toronto, CanadaPrincess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0032)Recruiting at this site
- Santiago, ChileCentro de Estudios Clínicos SAGA-CECSAGA ( Site 0041)Recruiting at this site
- Santiago, ChileFALP-UIDO ( Site 0040)Recruiting at this site
- Santiago, ChileBradfordhill ( Site 0042)Recruiting at this site
- Beijing, ChinaBeijing Friendship Hospital Affiliate of Capital University-Oncology ( Site 0417)Recruiting at this site
- Fuzhou, ChinaFujian Cancer Hospital ( Site 0419)Recruiting at this site
- Guangzhou, ChinaSouthern Medical University Nanfang Hospital-Depatrment of Respiratory and Critical Care Medicine ( Site 0413)Recruiting at this site
- Guangzhou, ChinaSun Yat-sen University Cancer Center-Internal medicine ( Site 0415)Recruiting at this site
- Wuhan, ChinaUnion Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 0418)Recruiting at this site
In total, worldwide, 67 of the 75 sites listed in the registry are recruiting; the other 8 are not currently recruiting.
Site status per the ClinicalTrials.gov registry (last update posted: October 7, 2026).
This status may have changed and says nothing about your eligibility: before taking any step, check with your oncologist or the site.
+ 37 more locations
Other identifiers
- MK-1084-001 · other identifier
- jRCT2041220034 · other registry
- 2022-501563-40-00 · other registry
- U1111-1281-2482 · other registry
See also
Other versions
These results are indicative and do not replace medical advice — discuss them with your doctor.