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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05067283




Registration number
NCT05067283
Ethics application status
Date submitted
1/10/2021
Date registered
5/10/2021

Titles & IDs
Public title
A Study of MK-1084 in KRAS Mutant Advanced Solid Tumors (MK-1084-001)
Scientific 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
Secondary ID [1] 0 0
MK-1084-001
Secondary ID [2] 0 0
1084-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MK-1084
Treatment: Other - Pembrolizumab
Treatment: Drugs - carboplatin
Treatment: Drugs - pemetrexed
Treatment: Other - cetuximab
Treatment: Drugs - oxaliplatin
Treatment: Drugs - leucovorin
Treatment: Drugs - 5-fluorouracil

Experimental: Arm 1 - Participants will receive daily oral escalating doses of up to 800 mg of MK-1084 until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety.

Experimental: Arm 2 - Participants will receive MK-1084 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 MK-1084 will continue until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety.

Experimental: Arm 3 - Participants will receive alternate formulation of MK-1084 until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety.

Experimental: Arm 4 - Participants will receive MK-1084 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.

Experimental: Arm 5 - Participants will receive MK-1084 daily oral dose plus an intravenous infusion of cetuximab (per label) every 2 weeks of each 28-day cycle.

Experimental: Arm 6 - Participants will receive MK-1084 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.


Treatment: Drugs: MK-1084
Oral dose

Treatment: Other: Pembrolizumab
Intravenous infusion of 200 mg

Treatment: Drugs: carboplatin
Per label

Treatment: Drugs: pemetrexed
Per label

Treatment: Other: cetuximab
Per label

Treatment: Drugs: oxaliplatin
Per label

Treatment: Drugs: leucovorin
Per label

Treatment: Drugs: 5-fluorouracil
Per label
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Who Experience a Dose-Limiting Toxicity (DLT)
Timepoint [1] 0 0
Up to ~21 days
Primary outcome [2] 0 0
Number of Participants Who Experience an Adverse Event (AE)
Timepoint [2] 0 0
Up to ~56 months
Primary outcome [3] 0 0
Number of Participants Who Discontinue Study Treatment Due to an AE
Timepoint [3] 0 0
Up to ~56 months
Secondary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
Up to ~56 months
Secondary outcome [2] 0 0
Duration of Response (DOR)
Timepoint [2] 0 0
Up to ~56 months
Secondary outcome [3] 0 0
Mean Plasma Concentration of MK-1084
Timepoint [3] 0 0
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)
Secondary outcome [4] 0 0
Maximum Concentration (Cmax) of MK-1084
Timepoint [4] 0 0
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).
Secondary outcome [5] 0 0
Time to Maximum Concentration (Tmax) of MK-1084
Timepoint [5] 0 0
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)
Secondary outcome [6] 0 0
Minimum Concentration (Cmin) of MK-1084
Timepoint [6] 0 0
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)
Secondary outcome [7] 0 0
Area Under the Concentration Time-Curve 0-12 Hours (AUC 0-12) of MK-1084
Timepoint [7] 0 0
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)
Secondary outcome [8] 0 0
Area Under the Concentration Time-Curve 0-24 Hours (AUC 0-24) of MK-1084
Timepoint [8] 0 0
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)
Secondary outcome [9] 0 0
Half-Life (t1/2) of MK-1084
Timepoint [9] 0 0
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)

Eligibility
Key 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: 3L/4L metastatic colorectal cancer (mCRC)
* Has histologically or cytologically confirmed diagnosis of unresectable and metastatic colorectal adenocarcinoma with histological or blood-based confirmation of KRAS G12C mutation
* Previous treatment failure of 2 or 3 previous lines 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/12/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
19/08/2027
Actual
Sample size
Target
830
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse ( Site 0002) - Camperdown
Recruitment hospital [2] 0 0
Liverpool Hospital-Medical Oncology ( Site 0001) - Liverpool
Recruitment hospital [3] 0 0
Westmead Hospital-Department of Medical Oncology ( Site 0006) - Westmead
Recruitment hospital [4] 0 0
Monash Health-Oncology Research ( Site 0003) - Clayton
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2170 - Liverpool
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
New Jersey
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Virginia
Country [6] 0 0
United States of America
State/province [6] 0 0
Wisconsin
Country [7] 0 0
Canada
State/province [7] 0 0
Alberta
Country [8] 0 0
Canada
State/province [8] 0 0
New Brunswick
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
Chile
State/province [10] 0 0
Araucania
Country [11] 0 0
Chile
State/province [11] 0 0
Region M. De Santiago
Country [12] 0 0
China
State/province [12] 0 0
Beijing
Country [13] 0 0
China
State/province [13] 0 0
Fujian
Country [14] 0 0
China
State/province [14] 0 0
Guangdong
Country [15] 0 0
China
State/province [15] 0 0
Hubei
Country [16] 0 0
China
State/province [16] 0 0
Jilin
Country [17] 0 0
China
State/province [17] 0 0
Shanghai
Country [18] 0 0
China
State/province [18] 0 0
Zhejiang
Country [19] 0 0
Denmark
State/province [19] 0 0
Syddanmark
Country [20] 0 0
Israel
State/province [20] 0 0
Haifa
Country [21] 0 0
Israel
State/province [21] 0 0
Jerusalem
Country [22] 0 0
Israel
State/province [22] 0 0
Kfar Saba
Country [23] 0 0
Israel
State/province [23] 0 0
Ramat Gan
Country [24] 0 0
Italy
State/province [24] 0 0
Lombardia
Country [25] 0 0
Italy
State/province [25] 0 0
Toscana
Country [26] 0 0
Italy
State/province [26] 0 0
Napoli
Country [27] 0 0
Japan
State/province [27] 0 0
Chiba
Country [28] 0 0
Japan
State/province [28] 0 0
Kanagawa
Country [29] 0 0
Japan
State/province [29] 0 0
Shizuoka
Country [30] 0 0
Japan
State/province [30] 0 0
Tokyo
Country [31] 0 0
Korea, Republic of
State/province [31] 0 0
Seoul
Country [32] 0 0
New Zealand
State/province [32] 0 0
Canterbury
Country [33] 0 0
Panama
State/province [33] 0 0
Panama City
Country [34] 0 0
Poland
State/province [34] 0 0
Mazowieckie
Country [35] 0 0
Poland
State/province [35] 0 0
Pomorskie
Country [36] 0 0
Poland
State/province [36] 0 0
Wielkopolskie
Country [37] 0 0
Poland
State/province [37] 0 0
Zachodniopomorskie
Country [38] 0 0
Spain
State/province [38] 0 0
Madrid, Comunidad De
Country [39] 0 0
Spain
State/province [39] 0 0
Barcelona
Country [40] 0 0
Switzerland
State/province [40] 0 0
Sankt Gallen
Country [41] 0 0
Switzerland
State/province [41] 0 0
Ticino
Country [42] 0 0
Taiwan
State/province [42] 0 0
Kaohsiung
Country [43] 0 0
Taiwan
State/province [43] 0 0
Tainan
Country [44] 0 0
Taiwan
State/province [44] 0 0
Taipei
Country [45] 0 0
Turkey
State/province [45] 0 0
Izmir
Country [46] 0 0
Turkey
State/province [46] 0 0
Kayseri
Country [47] 0 0
Turkey
State/province [47] 0 0
Ankara
Country [48] 0 0
Ukraine
State/province [48] 0 0
Cherkaska Oblast
Country [49] 0 0
Ukraine
State/province [49] 0 0
Ivano-Frankivska Oblast
Country [50] 0 0
Ukraine
State/province [50] 0 0
Rivnenska Oblast

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Trialsites@msd.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05067283