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NCT05067283PHASE1Recruiting

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

Merck Sharp & Dohme LLC

Start Date

12/17/2021

Completion Date

2/25/2030

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

DRUG

Calderasib

BIOLOGICAL

Pembrolizumab

DRUG

carboplatin

DRUG

pemetrexed

BIOLOGICAL

cetuximab

DRUG

oxaliplatin

DRUG

leucovorin

DRUG

5-fluorouracil

Interested in This Trial?

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Conditions

Advanced Solid Tumors

Locations

Moffitt Cancer Center ( Site 0261)

Tampa, Florida 33612

United States

START Midwest ( Site 0267)

Grand Rapids, Michigan 49546

United States

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

Hackensack, New Jersey 07601

United States

Laura and Isaac Perlmutter Cancer Center ( Site 0270)

New York, New York 10016

United States

NEXT Virginia ( Site 0271)

Fairfax, Virginia 22031

United States

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

Milwaukee, Wisconsin 53226

United States

Instituto Alexander Fleming ( Site 0434)

Ciudad Autónoma de Buenos Aires, Buenos Aires C1426ANZ

Argentina

Sanatorio Parque ( Site 0456)

Rosario, Santa Fe Province S2000DSV

Argentina

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

La Rioja, F5300COE

Argentina

Chris O'Brien Lifehouse ( Site 0002)

Camperdown, New South Wales 2050

Australia

Liverpool Hospital-Medical Oncology ( Site 0001)

Liverpool, New South Wales 2170

Australia

Westmead Hospital ( Site 0006)

Westmead, New South Wales 2145

Australia

Monash Health-Oncology Research ( Site 0003)

Clayton, Victoria 3168

Australia

Cross Cancer Institute ( Site 0033)

Edmonton, Alberta T6G 1Z2

Canada

The Moncton Hospital ( Site 0037)

Moncton, New Brunswick E1C 6Z8

Canada

Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0030)

Hamilton, Ontario L8V 5C2

Canada

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

Kingston, Ontario K7L 2V7

Canada

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

Toronto, Ontario M5G 2M9

Canada

James Lind Centro de Investigacion del Cancer ( Site 0043)

Temuco, Araucania 4800827

Chile

Centro de Estudios Clínicos SAGA-CECSAGA ( Site 0041)

Santiago, Region M. de Santiago 7500653

Chile

FALP-UIDO ( Site 0040)

Santiago, Region M. de Santiago 7500921

Chile

Bradfordhill ( Site 0042)

Santiago, Region M. de Santiago 8420383

Chile

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

Beijing, Beijing Municipality 100050

China

Fujian Cancer Hospital ( Site 0419)

Fuzhou, Fujian 350014

China

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

Guangzhou, Guangdong 510515

China

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

Guangzhou, Guangdong 511400

China

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

Wuhan, Hubei 430048

China

Jilin Cancer Hospital-oncology department ( Site 0412)

Changchun, Jilin 132000

China

Shanghai Chest Hospital-Oncology department ( Site 0410)

Shanghai, Shanghai Municipality 200030

China

Shanghai East Hospital ( Site 0416)

Shanghai, Shanghai Municipality 200120

China

Zhejiang Cancer Hospital-Thoracic oncology ( Site 0411)

Hangzhou, Zhejiang 310022

China

Odense Universitetshospital-Department of oncology ( Site 0421)

Odense, Region Syddanmark 5000

Denmark

Rambam Health Care Campus-Oncology ( Site 0090)

Haifa, 3109601

Israel

Shaare Zedek Medical Center-Oncology ( Site 0092)

Jerusalem, 9103102

Israel

Hadassah Medical Center-Oncology ( Site 0094)

Jerusalem, 9112001

Israel

Meir Medical Center. ( Site 0091)

Kfar Saba, 4428164

Israel

Sheba Medical Center-ONCOLOGY ( Site 0093)

Ramat Gan, 5265601

Israel

Humanitas ( Site 0113)

Rozzano, Lombardy 20089

Italy

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

Siena, Tuscany 53100

Italy

Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0110)

Naples, 80131

Italy

National Cancer Center Hospital East ( Site 0404)

Kashiwa, Chiba 277-8577

Japan

Kanagawa Cancer Center ( Site 0402)

Yokohama, Kanagawa 241-8515

Japan

Shizuoka Cancer Center ( Site 0401)

Nakatogari, Shizuoka 411-8777

Japan

National Cancer Center Hospital ( Site 0403)

Chuo-ku, Tokyo 104-0045

Japan

Cancer Institute Hospital of JFCR ( Site 0400)

Koto, Tokyo 135-8550

Japan

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

Kaunas, Kaunas County 45433

Lithuania

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

Vilnius, LT-08406

Lithuania

Sarawak General Hospital ( Site 0453)

Kuching, Sarawak 93586

Malaysia

New Zealand Clinical Research (Christchurch) ( Site 0004)

Christchurch, Canterbury 8011

New Zealand

Centro Oncologico de Panama ( Site 0160)

Panama City, 082410

Panama

Centro Hemato Oncológico Paitilla ( Site 0163)

Panama City, 0832-00752

Panama

Uniwersytecki Szpital Kliniczny w Poznaniu ( Site 0172)

Poznan, Greater Poland Voivodeship 60-569

Poland

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

Warsaw, Masovian Voivodeship 02-781

Poland

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

Gdansk, Pomeranian Voivodeship 80-952

Poland

Oddzial Onkologii Klinicznej z Pododdzialem Chemioterapii Jednodniowej ( Site 0173)

Koszalin, West Pomeranian Voivodeship 75-581

Poland

Seoul National University Hospital ( Site 0191)

Seoul, 03080

South Korea

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

Seoul, 06351

South Korea

Clinica Universidad de Navarra ( Site 0213)

Madrid, Madrid, Comunidad de 28027

Spain

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

Madrid, Madrid, Comunidad de 28040

Spain

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

Barcelona, 08035

Spain

Cantonal Hospital St.Gallen ( Site 0224)

Sankt Gallen, Canton of St. Gallen 9007

Switzerland

Ospedale Regionale Bellinzona e Valli ( Site 0220)

Bellinzona, Canton Ticino 6500

Switzerland

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

Kaohsiung Niao Sung Dist, Kaohsiung 83301

Taiwan

National Cheng Kung University Hospital ( Site 0444)

Tainan, 704

Taiwan

National Taiwan University Hospital-Oncology ( Site 0443)

Taipei, 10002

Taiwan

Ege University Medicine of Faculty ( Site 0231)

Bornova, İzmir 35100

Turkey (Türkiye)

Erciyes University ( Site 0232)

Talas, Kayseri 38039

Turkey (Türkiye)

Hacettepe Universite Hastaneleri-oncology hospital ( Site 0234)

Ankara, 06230

Turkey (Türkiye)

Ankara City Hospital-oncology ( Site 0233)

Ankara, 6800

Turkey (Türkiye)

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

Cherkasy, Cherkasy Oblast 18009

Ukraine

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

Ivano-Frankivsk, Ivano-Frankivsk Oblast 76018

Ukraine

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

Kropyvnytskyi, Kirovohrad Oblast 25006

Ukraine

Rivne Regional Clinical Hospital ( Site 0257)

Rivne, Rivne Oblast 33007

Ukraine

ME RIVNE REGIONAL ANTITUMOR CENTER ( Site 0259)

Rivne, Rivne Oblast 33010

Ukraine

Uzhhorod Multispecialty City Clinical Hospital ( Site 0258)

Uzhhorod, Zakarpattia Oblast 88017

Ukraine