Phase 1 Study of MK-1084 in KRAS mutant advanced solid tumors

JRCT ID: jRCT2041220034

Registered date:15/06/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Solid tumor
• Date of first enrollment: 04/08/2022
• Target sample size: 3
• Countries of recruitment: Australia,Japan,New Zealand,Japan,South Korea,Japan,China,Japan,France,Japan,Italy,Japan,Lithuania,Japan,Norway,Japan,Spain,Japan,Switzerland,Japan,Israel,Japan,Poland,Japan,Russia,Japan,Turkey,Japan,Ukraine,Japan,Chile,Japan,Panama,Japan,Canada,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

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

Outcome(s)

• Primary Outcome: Dose-limiting toxicities (DLTs), Adverse events (AEs), Discontinuation of the study due to an AE

Secondary Outcome

Objective response, Duration of response, PK
parameters,

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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
- Untreated locally advanced unresectable or metastatic colorectal adenocarcinoma with histologically or blood-based confirmation of KRAS G12C mutation

Exclude criteria

- Has received chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation)
- 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
- Has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- 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.

Related Information

• Primary Sponsor: Fujita Tomoko
• Secondary ID(s): NCT05067283