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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
19/08/2026
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
New Brunswick
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Chile
State/province [9] 0 0
Araucania
Country [10] 0 0
Chile
State/province [10] 0 0
Region M. De Santiago
Country [11] 0 0
China
State/province [11] 0 0
Beijing
Country [12] 0 0
China
State/province [12] 0 0
Fujian
Country [13] 0 0
China
State/province [13] 0 0
Guangdong
Country [14] 0 0
China
State/province [14] 0 0
Hubei
Country [15] 0 0
China
State/province [15] 0 0
Jilin
Country [16] 0 0
China
State/province [16] 0 0
Shanghai
Country [17] 0 0
China
State/province [17] 0 0
Zhejiang
Country [18] 0 0
Denmark
State/province [18] 0 0
Syddanmark
Country [19] 0 0
Israel
State/province [19] 0 0
Haifa
Country [20] 0 0
Israel
State/province [20] 0 0
Jerusalem
Country [21] 0 0
Israel
State/province [21] 0 0
Kfar Saba
Country [22] 0 0
Israel
State/province [22] 0 0
Ramat Gan
Country [23] 0 0
Italy
State/province [23] 0 0
Lombardia
Country [24] 0 0
Italy
State/province [24] 0 0
Toscana
Country [25] 0 0
Italy
State/province [25] 0 0
Napoli
Country [26] 0 0
Japan
State/province [26] 0 0
Chiba
Country [27] 0 0
Japan
State/province [27] 0 0
Kanagawa
Country [28] 0 0
Japan
State/province [28] 0 0
Shizuoka
Country [29] 0 0
Japan
State/province [29] 0 0
Tokyo
Country [30] 0 0
Korea, Republic of
State/province [30] 0 0
Seoul
Country [31] 0 0
New Zealand
State/province [31] 0 0
Canterbury
Country [32] 0 0
Panama
State/province [32] 0 0
Panama City
Country [33] 0 0
Poland
State/province [33] 0 0
Mazowieckie
Country [34] 0 0
Poland
State/province [34] 0 0
Pomorskie
Country [35] 0 0
Poland
State/province [35] 0 0
Wielkopolskie
Country [36] 0 0
Poland
State/province [36] 0 0
Zachodniopomorskie
Country [37] 0 0
Spain
State/province [37] 0 0
Madrid, Comunidad De
Country [38] 0 0
Spain
State/province [38] 0 0
Barcelona
Country [39] 0 0
Switzerland
State/province [39] 0 0
Sankt Gallen
Country [40] 0 0
Switzerland
State/province [40] 0 0
Ticino
Country [41] 0 0
Taiwan
State/province [41] 0 0
Kaohsiung
Country [42] 0 0
Taiwan
State/province [42] 0 0
Tainan
Country [43] 0 0
Taiwan
State/province [43] 0 0
Taipei
Country [44] 0 0
Turkey
State/province [44] 0 0
Ankara
Country [45] 0 0
Turkey
State/province [45] 0 0
Izmir
Country [46] 0 0
Turkey
State/province [46] 0 0
Kayseri

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
[email protected]
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