Clinical trial NCT05067283: A Study of MK-1084 in KRAS Mutant Advanced Solid Tumors (MK-1084-001)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2021-10-05
Enrollment: 830
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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: 2L+NSCLC
* Has histologically or cytologically confirmed diagnosis of unresectable or metastatic NSCLC with histological or blood-based confirmation of KRAS G12C mutation
* 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

Primary outcomes:
measure: Number of Participants Who Experience a Dose-Limiting Toxicity (DLT)
timeFrame: Up to ~21 days
measure: Number of Participants Who Experience an Adverse Event (AE)
timeFrame: Up to ~56 months
measure: Number of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to ~56 months
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to ~56 months
measure: Duration of Response (DOR)
timeFrame: Up to ~56 months
measure: Mean Plasma Concentration of MK-1084
timeFrame: 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)
measure: Maximum Concentration (Cmax) of MK-1084
timeFrame: 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).
measure: Time to Maximum Concentration (Tmax) of MK-1084
timeFrame: 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)
measure: Minimum Concentration (Cmin) of MK-1084
timeFrame: 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)
measure: Area Under the Concentration Time-Curve 0-12 Hours (AUC 0-12) of MK-1084
timeFrame: 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)
measure: Area Under the Concentration Time-Curve 0-24 Hours (AUC 0-24) of MK-1084
timeFrame: 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)
measure: Half-Life (t1/2) of MK-1084
timeFrame: 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)
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center ( Site 0261)
state: Florida
city: Grand Rapids
country: United States
facility: START Midwest ( Site 0267)
state: Michigan
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center ( Site 0260)
state: New Jersey
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center ( Site 0270)
state: New York
city: Fairfax
country: United States
facility: NEXT Virginia ( Site 0271)
state: Virginia
city: Milwaukee
country: United States
facility: MEDICAL COLLEGE OF WISCONSIN-Cancer Center Clinical Trials Office ( Site 0262)
state: Wisconsin
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse ( Site 0002)
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital-Medical Oncology ( Site 0001)
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital ( Site 0006)
state: New South Wales
city: Clayton
country: Australia
facility: Monash Health-Oncology Research ( Site 0003)
state: Victoria
city: Edmonton
country: Canada
facility: Cross Cancer Institute ( Site 0033)
state: Alberta
city: Moncton
country: Canada
facility: The Moncton Hospital ( Site 0037)
state: New Brunswick
city: Hamilton
country: Canada
facility: Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0030)
state: Ontario
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre-Kingston General Hospital Site ( Site 0036)
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0032)
state: Ontario
city: Temuco
country: Chile
facility: James Lind Centro de Investigacion del Cancer ( Site 0043)
state: Araucania
city: Santiago.
country: Chile
facility: Centro de Estudios Clínicos SAGA-CECSAGA ( Site 0041)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: FALP-UIDO ( Site 0040)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Bradfordhill ( Site 0042)
state: Region M. De Santiago
city: Beijing
country: China
facility: Beijing Friendship Hospital Affiliate of Capital University-Oncology ( Site 0417)
state: Beijing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital ( Site 0419)
state: Fujian
city: Guangzhou
country: China
facility: Southern Medical University Nanfang Hospital-Depatrment of Respiratory and Critical Care Medicine ( Site 0413)
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center-Internal medicine ( Site 0415)
state: Guangdong
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 0418)
state: Hubei
city: Changchun
country: China
facility: Jilin Cancer Hospital-oncology department ( Site 0412)
state: Jilin
city: Shanghai
country: China
facility: Shanghai Chest Hospital-Oncology department ( Site 0410)
state: Shanghai
city: Shanghai
country: China
facility: Shanghai East Hospital ( Site 0416)
state: Shanghai
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital-Thoracic oncology ( Site 0411)
state: Zhejiang
city: Odense
country: Denmark
facility: Odense Universitetshospital-Department of oncology ( Site 0421)
state: Syddanmark
city: Haifa
country: Israel
facility: Rambam Health Care Campus-Oncology ( Site 0090)
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center-Oncology ( Site 0092)
city: Jerusalem
country: Israel
facility: Hadassah Medical Center-Oncology ( Site 0094)
city: Kfar Saba
country: Israel
facility: Meir Medical Center. ( Site 0091)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center-ONCOLOGY ( Site 0093)
city: Rozzano
country: Italy
facility: Humanitas ( Site 0113)
state: Lombardia
city: Siena
country: Italy
facility: ospedale le scotte-U.O.C. Immunoterapia Oncologica ( Site 0111)
state: Toscana
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0110)
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East ( Site 0404)
state: Chiba
city: Yokohama
country: Japan
facility: Kanagawa Cancer Center ( Site 0402)
state: Kanagawa
city: Nagaizumi
country: Japan
facility: Shizuoka Cancer Center ( Site 0401)
state: Shizuoka
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital ( Site 0403)
state: Tokyo
city: Koto
country: Japan
facility: Cancer Institute Hospital of JFCR ( Site 0400)
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 0191)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center-Division of Hematology/Oncology ( Site 0193)
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kauno klinikos ( Site 0121)
state: Kauno Apskritis
city: Christchurch
country: New Zealand
facility: New Zealand Clinical Research (Christchurch) ( Site 0004)
state: Canterbury
city: Panama City
country: Panama
facility: Centro Oncologico de Panama ( Site 0160)
city: Panama City
country: Panama
facility: Centro Hemato Oncológico Paitilla ( Site 0163)
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 0170)
state: Mazowieckie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0171)
state: Pomorskie
city: Poznan
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Poznaniu ( Site 0172)
state: Wielkopolskie
city: Koszalin
country: Poland
facility: Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0173)
state: Zachodniopomorskie
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra ( Site 0213)
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz-START Madrid-FJD ( Site 0211)
state: Madrid, Comunidad De
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron-Oncology ( Site 0212)
city: St.Gallen
country: Switzerland
facility: Cantonal Hospital St.Gallen ( Site 0224)
state: Sankt Gallen
city: Bellinzona
country: Switzerland
facility: Ospedale Regionale Bellinzona e Valli ( Site 0220)
state: Ticino
city: Kaohsiung Niao Sung Dist
country: Taiwan
facility: Chang Gung Memorial Hospital at Kaohsiung-Oncology and Hematology ( Site 0445)
state: Kaohsiung
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital ( Site 0444)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital-Oncology ( Site 0443)
city: Bornova
country: Turkey
facility: Ege University Medicine of Faculty ( Site 0231)
state: Izmir
city: Talas
country: Turkey
facility: Erciyes University ( Site 0232)
state: Kayseri
city: Ankara
country: Turkey
facility: Hacettepe Universite Hastaneleri-oncology hospital ( Site 0234)
city: Ankara
country: Turkey
facility: Ankara City Hospital-oncology ( Site 0233)
city: Cherkasy
country: Ukraine
facility: MNPE ClinCenter of Oncology,Hematology,Transplantology and Palliative Care of CherkasyRegCouncil ( Site 0254)
state: Cherkaska Oblast
city: Ivano-Frankivsk
country: Ukraine
facility: Communal Non-Commercial Enterprise Prykarpatski Clinical Onc-Chemotherapy department ( Site 0251)
state: Ivano-Frankivska Oblast
city: Kropyvnytskyi
country: Ukraine
facility: Private Enterprise Private Manufacturing Company Acinus-Medical and Diagnostic Centre ( Site 0255)
state: Kirovohradska Oblast
city: Rivne
country: Ukraine
facility: Rivne Regional Clinical Hospital ( Site 0257)
state: Rivnenska Oblast
city: Uzhhorod
country: Ukraine
facility: Uzhhorod Multispecialty City Clinical Hospital ( Site 0258)
state: Zakarpatska Oblast
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: