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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Biological: Pembrolizumab; Drug: carboplatin; Drug: pemetrexed; Biological: cetuximab; Drug: oxaliplatin; Drug: leucovorin; Drug: 5-fluorouracil; Drug: Calderasib

• Study Type: Interventional
• Enrollment (Estimated): 830
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@msd.com

Study Locations

• Argentina
  • La Rioja, Argentina, F5300COE
    • Recruiting
    • Fundación CORI para la Investigación y Prevención del Cáncer ( Site 0438)
    • Contact: Study Coordinator; Phone Number: +549380 4425438
  • Buenos Aires
    • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1426ANZ
      • Recruiting
      • Instituto Alexander Fleming ( Site 0434)
      • Contact: Study Coordinator; Phone Number: +541132218900
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, S2000DSV
      • Recruiting
      • Sanatorio Parque ( Site 0456)
      • Contact: Study Coordinator; Phone Number: 5493416955611
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Chris O'Brien Lifehouse ( Site 0002)
      • Contact: Study Coordinator; Phone Number: 61285140162
    • Liverpool, New South Wales, Australia, 2170
      • Recruiting
      • Liverpool Hospital-Medical Oncology ( Site 0001)
      • Contact: Study Coordinator; Phone Number: 61287389744
    • Westmead, New South Wales, Australia, 2145
      • Recruiting
      • Westmead Hospital ( Site 0006)
      • Contact: Study Coordinator; Phone Number: +61403170371
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Recruiting
      • Monash Health-Oncology Research ( Site 0003)
      • Contact: Study Coordinator; Phone Number: 6385722429
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Recruiting
      • Cross Cancer Institute ( Site 0033)
      • Contact: Study Coordinator; Phone Number: 780-908-8213
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • Recruiting
      • The Moncton Hospital ( Site 0037)
      • Contact: Study Coordinator; Phone Number: 506-857-5104
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Recruiting
      • Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0030)
      • Contact: Study Coordinator; Phone Number: 905-387-9495
    • Kingston, Ontario, Canada, K7L 2V7
      • Recruiting
      • Kingston Health Sciences Centre-Kingston General Hospital Site ( Site 0036)
      • Contact: Study Coordinator; Phone Number: 613-549-6666x4502
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0032)
      • Contact: Study Coordinator; Phone Number: 416-946-4501
• Chile
  • Araucania
    • Temuco, Araucania, Chile, 4800827
      • Completed
      • James Lind Centro de Investigacion del Cancer ( Site 0043)
  • Region M. de Santiago
    • Santiago, Region M. de Santiago, Chile, 7500653
      • Recruiting
      • Centro de Estudios Clínicos SAGA-CECSAGA ( Site 0041)
      • Contact: Study Coordinator; Phone Number: +56 9 9161 2199
    • Santiago, Region M. de Santiago, Chile, 7500921
      • Recruiting
      • FALP-UIDO ( Site 0040)
      • Contact: Study Coordinator; Phone Number: +56981369487
    • Santiago, Region M. de Santiago, Chile, 8420383
      • Recruiting
      • Bradfordhill ( Site 0042)
      • Contact: Study Coordinator; Phone Number: +56998744662
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100050
      • Recruiting
      • Beijing Friendship Hospital Affiliate of Capital University-Oncology ( Site 0417)
      • Contact: Study Coordinator; Phone Number: 01063138585
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Recruiting
      • Fujian Cancer Hospital ( Site 0419)
      • Contact: Study Coordinator; Phone Number: 0591-62752500
  • Guangdong
    • Guangzhou, Guangdong, China, 511400
      • Recruiting
      • Sun Yat-sen University Cancer Center-Internal medicine ( Site 0415)
      • Contact: Study Coordinator; Phone Number: 86 02087343801
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Southern Medical University Nanfang Hospital-Depatrment of Respiratory and Critical Care Medicine ( Site 0413)
      • Contact: Study Coordinator; Phone Number: 8620 62787110
  • Hubei
    • Wuhan, Hubei, China, 430048
      • Recruiting
      • Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 0418)
      • Contact: Study Coordinator; Phone Number: 027-85726685
  • Jilin
    • Changchun, Jilin, China, 132000
      • Completed
      • Jilin Cancer Hospital-oncology department ( Site 0412)
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200030
      • Recruiting
      • Shanghai Chest Hospital-Oncology department ( Site 0410)
      • Contact: Study Coordinator; Phone Number: 021-22200000
    • Shanghai, Shanghai Municipality, China, 200120
      • Recruiting
      • Shanghai East Hospital ( Site 0416)
      • Contact: Study Coordinator; Phone Number: +86 13764694939
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Recruiting
      • Zhejiang Cancer Hospital-Thoracic oncology ( Site 0411)
      • Contact: Study Coordinator; Phone Number: 0571-88122092
• Denmark
  • Region Syddanmark
    • Odense, Region Syddanmark, Denmark, 5000
      • Recruiting
      • Odense Universitetshospital-Department of oncology ( Site 0421)
      • Contact: Study Coordinator; Phone Number: +45 66113333
• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Rambam Health Care Campus-Oncology ( Site 0090)
    • Contact: Study Coordinator; Phone Number: +97247776234
  • Jerusalem, Israel, 9103102
    • Recruiting
    • Shaare Zedek Medical Center-Oncology ( Site 0092)
    • Contact: Study Coordinator; Phone Number: +97226555768
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah Medical Center-Oncology ( Site 0094)
    • Contact: Study Coordinator; Phone Number: +97226776760
  • Kfar Saba, Israel, 4428164
    • Recruiting
    • Meir Medical Center. ( Site 0091)
    • Contact: Study Coordinator; Phone Number: 97297472414
  • Ramat Gan, Israel, 5265601
    • Recruiting
    • Sheba Medical Center-ONCOLOGY ( Site 0093)
    • Contact: Study Coordinator; Phone Number: +97235304498
• Italy
  • Naples, Italy, 80131
    • Recruiting
    • Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0110)
    • Contact: Study Coordinator; Phone Number: 08117770810
  • Lombardy
    • Rozzano, Lombardy, Italy, 20089
      • Recruiting
      • Humanitas ( Site 0113)
      • Contact: Study Coordinator; Phone Number: 00390282244559
  • Tuscany
    • Siena, Tuscany, Italy, 53100
      • Recruiting
      • ospedale le scotte-U.O.C. Immunoterapia Oncologica ( Site 0111)
      • Contact: Study Coordinator; Phone Number: 00390577586335
• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East ( Site 0404)
      • Contact: Study Coordinator; Phone Number: +81-4-7133-1111
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 241-8515
      • Recruiting
      • Kanagawa Cancer Center ( Site 0402)
      • Contact: Study Coordinator; Phone Number: +81-45-520-2222
  • Shizuoka
    • Nakatogari, Shizuoka, Japan, 411-8777
      • Recruiting
      • Shizuoka Cancer Center ( Site 0401)
      • Contact: Study Coordinator; Phone Number: +81-55-989-5222
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • Recruiting
      • National Cancer Center Hospital ( Site 0403)
      • Contact: Study Coordinator; Phone Number: +81-3-3542-2511
    • Koto, Tokyo, Japan, 135-8550
      • Recruiting
      • Cancer Institute Hospital of JFCR ( Site 0400)
      • Contact: Study Coordinator; Phone Number: +81-3-3520-0111
• Lithuania
  • Vilnius, Lithuania, LT-08406
    • Recruiting
    • Vilnius University Hospital Santaros Clinics Affiliate - National Cancer Center ( Site 0120)
    • Contact: Study Coordinator; Phone Number: +37064565101
  • Kaunas County
    • Kaunas, Kaunas County, Lithuania, 45433
      • Recruiting
      • Hospital of Lithuanian University of Health Sciences Kauno klinikos ( Site 0121)
      • Contact: Study Coordinator; Phone Number: +370 600 04799
• Malaysia
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Recruiting
      • Sarawak General Hospital ( Site 0453)
      • Contact: Study Coordinator; Phone Number: 082-276666
• New Zealand
  • Canterbury
    • Christchurch, Canterbury, New Zealand, 8011
      • Completed
      • New Zealand Clinical Research (Christchurch) ( Site 0004)
• Panama
  • Panama City, Panama, 082410
    • Recruiting
    • Centro Oncologico de Panama ( Site 0160)
    • Contact: Study Coordinator; Phone Number: +50764807461
  • Panama City, Panama, 0832-00752
    • Completed
    • Centro Hemato Oncológico Paitilla ( Site 0163)
• Poland
  • Greater Poland Voivodeship
    • Poznan, Greater Poland Voivodeship, Poland, 60-569
      • Recruiting
      • Uniwersytecki Szpital Kliniczny w Poznaniu ( Site 0172)
      • Contact: Study Coordinator; Phone Number: 48606228277
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-781
      • Recruiting
      • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 0170)
      • Contact: Study Coordinator; Phone Number: 48225463381
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-952
      • Recruiting
      • Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0171)
      • Contact: Study Coordinator; Phone Number: 48585844571
  • West Pomeranian Voivodeship
    • Koszalin, West Pomeranian Voivodeship, Poland, 75-581
      • Recruiting
      • Oddzial Onkologii Klinicznej z Pododdzialem Chemioterapii Jednodniowej ( Site 0173)
      • Contact: Study Coordinator; Phone Number: +48 94 348 84 00
• South Korea
  • Seoul, South Korea, 03080
    • Recruiting
    • Seoul National University Hospital ( Site 0191)
    • Contact: Study Coordinator; Phone Number: 82220722995
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center-Division of Hematology/Oncology ( Site 0193)
    • Contact: Study Coordinator; Phone Number: +82-2-3410-3459
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron-Oncology ( Site 0212)
    • Contact: Study Coordinator; Phone Number: 34 93 274 60 00x6988
  • Madrid, Comunidad de
    • Madrid, Madrid, Comunidad de, Spain, 28027
      • Recruiting
      • Clinica Universidad de Navarra ( Site 0213)
      • Contact: Study Coordinator; Phone Number: 34913531920x7501
    • Madrid, Madrid, Comunidad de, Spain, 28040
      • Recruiting
      • Hospital Universitario Fundación Jiménez Díaz-START Madrid-FJD ( Site 0211)
      • Contact: Study Coordinator; Phone Number: 34 91 550 48 00x2689
• Switzerland
  • Canton Ticino
    • Bellinzona, Canton Ticino, Switzerland, 6500
      • Recruiting
      • Ospedale Regionale Bellinzona e Valli ( Site 0220)
      • Contact: Study Coordinator; Phone Number: 41918118045
  • Canton of St. Gallen
    • Sankt Gallen, Canton of St. Gallen, Switzerland, 9007
      • Recruiting
      • Cantonal Hospital St.Gallen ( Site 0224)
      • Contact: Study Coordinator; Phone Number: 071/494 11 11
• Taiwan
  • Tainan, Taiwan, 704
    • Recruiting
    • National Cheng Kung University Hospital ( Site 0444)
    • Contact: Study Coordinator; Phone Number: +88662353535
  • Taipei, Taiwan, 10002
    • Recruiting
    • National Taiwan University Hospital-Oncology ( Site 0443)
    • Contact: Study Coordinator; Phone Number: +886223123456
  • Kaohsiung
    • Kaohsiung Niao Sung Dist, Kaohsiung, Taiwan, 83301
      • Recruiting
      • Chang Gung Memorial Hospital at Kaohsiung-Oncology and Hematology ( Site 0445)
      • Contact: Study Coordinator; Phone Number: 886-7-7317123
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06230
    • Recruiting
    • Hacettepe Universite Hastaneleri-oncology hospital ( Site 0234)
    • Contact: Study Coordinator; Phone Number: 905334318506
  • Ankara, Turkey (Türkiye), 6800
    • Recruiting
    • Ankara City Hospital-oncology ( Site 0233)
    • Contact: Study Coordinator; Phone Number: +90 312 552 60 00
  • Kayseri
    • Talas, Kayseri, Turkey (Türkiye), 38039
      • Completed
      • Erciyes University ( Site 0232)
  • İzmir
    • Bornova, İzmir, Turkey (Türkiye), 35100
      • Completed
      • Ege University Medicine of Faculty ( Site 0231)
• Ukraine
  • Cherkasy Oblast
    • Cherkasy, Cherkasy Oblast, Ukraine, 18009
      • Recruiting
      • MNPE ClinCenter of Oncology,Hematology,Transplantology and Palliative Care of CherkasyRegCouncil ( Site 0254)
      • Contact: Study Coordinator; Phone Number: +380472370123
  • Ivano-Frankivsk Oblast
    • Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine, 76018
      • Recruiting
      • Communal Non-Commercial Enterprise Prykarpatski Clinical Onc-Chemotherapy department ( Site 0251)
      • Contact: Study Coordinator; Phone Number: +380502094000
  • Kirovohrad Oblast
    • Kropyvnytskyi, Kirovohrad Oblast, Ukraine, 25006
      • Recruiting
      • Private Enterprise Private Manufacturing Company Acinus-Medical and Diagnostic Centre ( Site 0255)
      • Contact: Study Coordinator; Phone Number: +380522366001
  • Rivne Oblast
    • Rivne, Rivne Oblast, Ukraine, 33007
      • Completed
      • Rivne Regional Clinical Hospital ( Site 0257)
    • Rivne, Rivne Oblast, Ukraine, 33010
      • Recruiting
      • ME RIVNE REGIONAL ANTITUMOR CENTER ( Site 0259)
      • Contact: Study Coordinator; Phone Number: +380503802915
  • Zakarpattia Oblast
    • Uzhhorod, Zakarpattia Oblast, Ukraine, 88000
      • Recruiting
      • Uzhhorod Multispecialty City Clinical Hospital ( Site 0258)
      • Contact: Study Coordinator; Phone Number: +380312642332
• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center ( Site 0261)
      • Contact: Study Coordinator; Phone Number: 813-745-5995
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • START Midwest ( Site 0267)
      • Contact: Study Coordinator; Phone Number: 616-954-5554
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • John Theurer Cancer Center at Hackensack University Medical Center ( Site 0260)
      • Contact: Study Coordinator; Phone Number: 551-996-5900
  • New York
    • New York, New York, United States, 10016
      • Completed
      • Laura and Isaac Perlmutter Cancer Center ( Site 0270)
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Virginia ( Site 0271)
      • Contact: Study Coordinator; Phone Number: 703-280-5390
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • MEDICAL COLLEGE OF WISCONSIN-Cancer Center Clinical Trials Office ( Site 0262)
      • Contact: Study Coordinator; Phone Number: 414-805-0505

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 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 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
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Participants will receive daily oral escalating doses of up to 800 mg of calderasib until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety.	Drug: Calderasib; Oral dose; Other Names: MK-1084
Experimental: Arm 2; Participants will receive calderasib 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 calderasib will continue until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety.	Biological: Pembrolizumab; Intravenous infusion of 200 mg; Other Names: MK-3475; KEYTRUDA®; Drug: Calderasib; Oral dose; Other Names: MK-1084
Experimental: Arm 3; Participants will receive alternate formulation of calderasib until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety.	Drug: Calderasib; Oral dose; Other Names: MK-1084
Experimental: Arm 4; Participants will receive calderasib 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.	Biological: Pembrolizumab; Intravenous infusion of 200 mg; Other Names: MK-3475; KEYTRUDA®; Drug: carboplatin; Per label; Drug: pemetrexed; Per label; Drug: Calderasib; Oral dose; Other Names: MK-1084
Experimental: Arm 5; Participants will receive calderasib daily oral dose plus an intravenous infusion of cetuximab (per label) every 2 weeks of each 28-day cycle.	Biological: cetuximab; Per label; Drug: Calderasib; Oral dose; Other Names: MK-1084
Experimental: Arm 6; Participants will receive calderasib 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.	Biological: cetuximab; Per label; Drug: oxaliplatin; Per label; Drug: leucovorin; Per label; Drug: 5-fluorouracil; Per label; Drug: Calderasib; Oral dose; Other Names: MK-1084

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Mean Plasma Concentration of calderasib	Mean Plasma Concentration of calderasib 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)
Maximum Concentration (Cmax) of calderasib	Cmax of calderasib 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).
Time to Maximum Concentration (Tmax) of calderasib	Tmax of calderasib 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)
Minimum Concentration (Cmin) of calderasib	Cmin of calderasib 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)
Area Under the Concentration Time-Curve 0-12 Hours (AUC 0-12) of calderasib	AUC 0-12 of calderasib 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)
Area Under the Concentration Time-Curve 0-24 Hours (AUC 0-24) of calderasib	AUC 0-24 of calderasib 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)
Half-Life (t1/2) of calderasib	Half-Life (t1/2) of calderasib 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)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Ma X, Sloman DL, Duggal R, Anderson KD, Ballard JE, Bharathan I, Brynczka C, Gathiaka S, Henderson TJ, Lyons TW, Miller R, Munsell EV, Orth P, Otte RD, Palani A, Rankic DA, Robinson MR, Sather AC, Solban N, Song XS, Wen X, Xu Z, Yang Y, Yang R, Day PJ, Stoeck A, Bennett DJ, Han Y. Discovery of MK-1084: An Orally Bioavailable and Low-Dose KRASG12C Inhibitor. J Med Chem. 2024 Jul 11;67(13):11024-11052. doi: 10.1021/acs.jmedchem.4c00572. Epub 2024 Jun 26.

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2021
• Primary Completion (Estimated): February 25, 2030
• Study Completion (Estimated): February 25, 2030

Study Registration Dates

• First Submitted: October 1, 2021
• First Submitted That Met QC Criteria: October 1, 2021
• First Posted (Actual): October 5, 2021

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Oxaliplatin; Pemetrexed; Cetuximab; Fluorouracil; Carboplatin; Leucovorin; pembrolizumab
• Other Study ID Numbers: 1084-001; MK-1084-001 (Other Identifier: MSD); jRCT2041220034 (Registry Identifier: jRCT); 2022-501563-40-00 (Registry Identifier: EU CT); U1111-1281-2482 (Registry Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No