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

NCT05067283 | Recruiting Phase 1 FDA Drug

• 5 other identifiers: 1084-001MK-1084-001jRCT20412200342022-501563-40-00U1111-1281-2482
• Study Type: interventional
• Target: 830
• Locations: 21 countries
• Sites: 74

Brief 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.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (9)

• Objective Response Rate (ORR)

  Up to ~56 months

• Duration of Response (DOR)

  Up to ~56 months

• Mean Plasma Concentration of calderasib

  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

  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

  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)

Study Arms (6)

Arm 1

EXPERIMENTAL

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

Arm 2

EXPERIMENTAL

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.

Drug: Calderasib; Biological: Pembrolizumab

Arm 3

EXPERIMENTAL

Participants will receive alternate formulation of calderasib until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety.

Drug: Calderasib

Arm 4

EXPERIMENTAL

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.

Drug: Calderasib; Biological: Pembrolizumab; Drug: carboplatin; Drug: pemetrexed

Arm 5

EXPERIMENTAL

Participants will receive calderasib daily oral dose plus an intravenous infusion of cetuximab (per label) every 2 weeks of each 28-day cycle.

Drug: Calderasib; Biological: cetuximab

Arm 6

EXPERIMENTAL

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.

Drug: Calderasib; Biological: cetuximab; Drug: oxaliplatin; Drug: leucovorin; Drug: 5-fluorouracil

Interventions

Pembrolizumab BIOLOGICAL

Intravenous infusion of 200 mg

Also known as: KEYTRUDA®, MK-3475

Arm 2; Arm 4

carboplatin DRUG

Per label

Arm 4

pemetrexed DRUG

Per label

Arm 4

Calderasib DRUG

Oral dose

Also known as: MK-1084

Arm 1; Arm 2; Arm 3; Arm 4; Arm 5; Arm 6

cetuximab BIOLOGICAL

Per label

Arm 5; Arm 6

oxaliplatin DRUG

Per label

Arm 6

leucovorin DRUG

Per label

Arm 6

5-fluorouracil DRUG

Per label

Arm 6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (74)

Moffitt Cancer Center ( Site 0261)

Tampa, Florida, 33612, United States

RECRUITING

START Midwest ( Site 0267)

Grand Rapids, Michigan, 49546, United States

RECRUITING

John Theurer Cancer Center at Hackensack University Medical Center ( Site 0260)

Hackensack, New Jersey, 07601, United States

RECRUITING

Laura and Isaac Perlmutter Cancer Center ( Site 0270)

New York, New York, 10016, United States

COMPLETED

NEXT Virginia ( Site 0271)

Fairfax, Virginia, 22031, United States

RECRUITING

MEDICAL COLLEGE OF WISCONSIN-Cancer Center Clinical Trials Office ( Site 0262)

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Instituto Alexander Fleming ( Site 0434)

Ciudad Autónoma de Buenos Aires, Buenos Aires, C1426ANZ, Argentina

RECRUITING

Fundación CORI para la Investigación y Prevención del Cáncer ( Site 0438)

La Rioja, F5300COE, Argentina

RECRUITING

Chris O'Brien Lifehouse ( Site 0002)

Camperdown, New South Wales, 2050, Australia

RECRUITING

Liverpool Hospital-Medical Oncology ( Site 0001)

Liverpool, New South Wales, 2170, Australia

RECRUITING

Westmead Hospital ( Site 0006)

Westmead, New South Wales, 2145, Australia

RECRUITING

Monash Health-Oncology Research ( Site 0003)

Clayton, Victoria, 3168, Australia

RECRUITING

Cross Cancer Institute ( Site 0033)

Edmonton, Alberta, T6G 1Z2, Canada

RECRUITING

The Moncton Hospital ( Site 0037)

Moncton, New Brunswick, E1C 6Z8, Canada

RECRUITING

Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0030)

Hamilton, Ontario, L8V 5C2, Canada

RECRUITING

Kingston Health Sciences Centre-Kingston General Hospital Site ( Site 0036)

Kingston, Ontario, K7L 2V7, Canada

RECRUITING

Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0032)

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

James Lind Centro de Investigacion del Cancer ( Site 0043)

Temuco, Araucania, 4800827, Chile

COMPLETED

Centro de Estudios Clínicos SAGA-CECSAGA ( Site 0041)

Santiago, Region M. de Santiago, 7500653, Chile

RECRUITING

FALP-UIDO ( Site 0040)

Santiago, Region M. de Santiago, 7500921, Chile

RECRUITING

Bradfordhill ( Site 0042)

Santiago, Region M. de Santiago, 8420383, Chile

RECRUITING

Beijing Friendship Hospital Affiliate of Capital University-Oncology ( Site 0417)

Beijing, Beijing Municipality, 100050, China

RECRUITING

Fujian Cancer Hospital ( Site 0419)

Fuzhou, Fujian, 350014, China

RECRUITING

Southern Medical University Nanfang Hospital-Depatrment of Respiratory and Critical Care Medicine ( Site 0413)

Guangzhou, Guangdong, 510515, China

RECRUITING

Sun Yat-sen University Cancer Center-Internal medicine ( Site 0415)

Guangzhou, Guangdong, 511400, China

RECRUITING

Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 0418)

Wuhan, Hubei, 430048, China

RECRUITING

Jilin Cancer Hospital-oncology department ( Site 0412)

Changchun, Jilin, 132000, China

COMPLETED

Shanghai Chest Hospital-Oncology department ( Site 0410)

Shanghai, Shanghai Municipality, 200030, China

RECRUITING

Shanghai East Hospital ( Site 0416)

Shanghai, Shanghai Municipality, 200120, China

RECRUITING

Zhejiang Cancer Hospital-Thoracic oncology ( Site 0411)

Hangzhou, Zhejiang, 310022, China

RECRUITING

Odense Universitetshospital-Department of oncology ( Site 0421)

Odense, Region Syddanmark, 5000, Denmark

RECRUITING

Rambam Health Care Campus-Oncology ( Site 0090)

Haifa, 3109601, Israel

RECRUITING

Shaare Zedek Medical Center-Oncology ( Site 0092)

Jerusalem, 9103102, Israel

RECRUITING

Hadassah Medical Center-Oncology ( Site 0094)

Jerusalem, 9112001, Israel

RECRUITING

Meir Medical Center. ( Site 0091)

Kfar Saba, 4428164, Israel

RECRUITING

Sheba Medical Center-ONCOLOGY ( Site 0093)

Ramat Gan, 5265601, Israel

RECRUITING

Humanitas ( Site 0113)

Rozzano, Lombardy, 20089, Italy

RECRUITING

ospedale le scotte-U.O.C. Immunoterapia Oncologica ( Site 0111)

Siena, Tuscany, 53100, Italy

RECRUITING

Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0110)

Naples, 80131, Italy

RECRUITING

National Cancer Center Hospital East ( Site 0404)

Kashiwa, Chiba, 277-8577, Japan

RECRUITING

Kanagawa Cancer Center ( Site 0402)

Yokohama, Kanagawa, 241-8515, Japan

RECRUITING

Shizuoka Cancer Center ( Site 0401)

Nakatogari, Shizuoka, 411-8777, Japan

RECRUITING

National Cancer Center Hospital ( Site 0403)

Chuo-ku, Tokyo, 104-0045, Japan

RECRUITING

Cancer Institute Hospital of JFCR ( Site 0400)

Koto, Tokyo, 135-8550, Japan

RECRUITING

Hospital of Lithuanian University of Health Sciences Kauno klinikos ( Site 0121)

Kaunas, Kaunas County, 45433, Lithuania

RECRUITING

Vilnius University Hospital Santaros Clinics Affiliate - National Cancer Center ( Site 0120)

Vilnius, LT-08406, Lithuania

RECRUITING

Sarawak General Hospital ( Site 0453)

Kuching, Sarawak, 93586, Malaysia

RECRUITING

New Zealand Clinical Research (Christchurch) ( Site 0004)

Christchurch, Canterbury, 8011, New Zealand

COMPLETED

Centro Oncologico de Panama ( Site 0160)

Panama City, 082410, Panama

RECRUITING

Centro Hemato Oncológico Paitilla ( Site 0163)

Panama City, 0832-00752, Panama

COMPLETED

Uniwersytecki Szpital Kliniczny w Poznaniu ( Site 0172)

Poznan, Greater Poland Voivodeship, 60-569, Poland

RECRUITING

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 0170)

Warsaw, Masovian Voivodeship, 02-781, Poland

RECRUITING

Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0171)

Gdansk, Pomeranian Voivodeship, 80-952, Poland

RECRUITING

Oddzial Onkologii Klinicznej z Pododdzialem Chemioterapii Jednodniowej ( Site 0173)

Koszalin, West Pomeranian Voivodeship, 75-581, Poland

RECRUITING

Seoul National University Hospital ( Site 0191)

Seoul, 03080, South Korea

RECRUITING

Samsung Medical Center-Division of Hematology/Oncology ( Site 0193)

Seoul, 06351, South Korea

RECRUITING

Clinica Universidad de Navarra ( Site 0213)

Madrid, Madrid, Comunidad de, 28027, Spain

RECRUITING

Hospital Universitario Fundación Jiménez Díaz-START Madrid-FJD ( Site 0211)

Madrid, Madrid, Comunidad de, 28040, Spain

RECRUITING

Hospital Universitari Vall d'Hebron-Oncology ( Site 0212)

Barcelona, 08035, Spain

RECRUITING

Cantonal Hospital St.Gallen ( Site 0224)

Sankt Gallen, Canton of St. Gallen, 9007, Switzerland

RECRUITING

Ospedale Regionale Bellinzona e Valli ( Site 0220)

Bellinzona, Canton Ticino, 6500, Switzerland

RECRUITING

Chang Gung Memorial Hospital at Kaohsiung-Oncology and Hematology ( Site 0445)

Kaohsiung Niao Sung Dist, Kaohsiung, 83301, Taiwan

RECRUITING

National Cheng Kung University Hospital ( Site 0444)

Tainan, 704, Taiwan

RECRUITING

National Taiwan University Hospital-Oncology ( Site 0443)

Taipei, 10002, Taiwan

RECRUITING

Ege University Medicine of Faculty ( Site 0231)

Bornova, İzmir, 35100, Turkey (Türkiye)

COMPLETED

Erciyes University ( Site 0232)

Talas, Kayseri, 38039, Turkey (Türkiye)

COMPLETED

Hacettepe Universite Hastaneleri-oncology hospital ( Site 0234)

Ankara, 06230, Turkey (Türkiye)

RECRUITING

Ankara City Hospital-oncology ( Site 0233)

Ankara, 6800, Turkey (Türkiye)

RECRUITING

MNPE ClinCenter of Oncology,Hematology,Transplantology and Palliative Care of CherkasyRegCouncil ( Site 0254)

Cherkasy, Cherkasy Oblast, 18009, Ukraine

RECRUITING

Communal Non-Commercial Enterprise Prykarpatski Clinical Onc-Chemotherapy department ( Site 0251)

Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76018, Ukraine

RECRUITING

Private Enterprise Private Manufacturing Company Acinus-Medical and Diagnostic Centre ( Site 0255)

Kropyvnytskyi, Kirovohrad Oblast, 25006, Ukraine

RECRUITING

Rivne Regional Clinical Hospital ( Site 0257)

Rivne, Rivne Oblast, 33007, Ukraine

COMPLETED

ME RIVNE REGIONAL ANTITUMOR CENTER ( Site 0259)

Rivne, Rivne Oblast, 33010, Ukraine

RECRUITING

Uzhhorod Multispecialty City Clinical Hospital ( Site 0258)

Uzhhorod, Zakarpattia Oblast, 88000, Ukraine

RECRUITING

Related Publications (1)

• 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.

  PMID: 38924388 DERIVED

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Interventions

pembrolizumab; Carboplatin; Pemetrexed; Cetuximab; Oxaliplatin; Leucovorin; Fluorouracil

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2021
• First Posted: October 5, 2021
• Study Start: December 17, 2021
• Primary Completion (Estimated): February 25, 2030
• Study Completion (Estimated): February 25, 2030
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

NZ (1); CN (9); US (6); KR (2); CL (4); IL (5); IT (3); JP (5); CA (5); PL (4); TW (3); CH (2); UA (6); PA (2); MY (1); LI (2); ES (3); DK (1); AU (4); TU (4); AR (2)