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Tyrosine Kinase Inhibitor

MEK162 + Imatinib for Gastrointestinal Stromal Tumor

Phase 1 & 2

Waitlist Available

Led By Ping Chi, MD, PhD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have pathologically confirmed GIST.

In the Phase Ib portion, patients must have locally advanced or metastatic GIST and have progressed on imatinib.

Must not have

Patients have a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).

Patients have a history or current evidence of Central Serous Retinopathy (CSR) or retinal vein occlusion (RVO) or predisposing factors to CSR or RVO (i.e. uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, hyperviscosity or hypercoagulability syndromes).

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the effects of two drugs, MEK162 and imatinib, on Gastrointestinal Stromal Tumor (GIST). The funding for this trial comes from the FDA Office of Orphan Products Development and Array/Pfizer.

Who is the study for?

Adults with confirmed Gastrointestinal Stromal Tumor (GIST) who can take pills, have not been treated before or are off previous treatment for 3 months. They must be in good health based on specific blood tests and heart function, agree to use birth control if necessary, and cannot have a history of certain eye diseases, uncontrolled medical conditions like diabetes or hypertension, recent major surgery side effects, or active infections.

What is being tested?

The trial is testing the combination of two drugs: MEK162 and Imatinib Mesylate (Gleevec), which patients will take orally. The study aims to see how well these drugs work together against untreated advanced GIST by monitoring their effects through biopsies and regular blood draws.

What are the potential side effects?

Possible side effects include typical reactions from cancer medications such as fatigue, nausea, skin rash, vision changes due to potential eye-related risks associated with MEK162. There may also be liver function changes and muscle pain related to elevated creatinine phosphokinase levels.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My diagnosis is a gastrointestinal stromal tumor (GIST).

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My GIST has worsened despite taking imatinib.

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I am 18 years old or older.

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I am fully active or restricted in physically strenuous activity but can do light work.

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My kidney, liver, and blood tests are within normal ranges.

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My heart is strong enough for the trial (LVEF ≥50% and QTc ≤480 ms).

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I can take pills by mouth.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a severe illness like uncontrolled diabetes, kidney disease, or an active infection.

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I have or am at risk for eye conditions like CSR or RVO due to factors like uncontrolled diabetes or glaucoma.

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I have a long-term liver condition, such as cirrhosis.

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I have a history of eye diseases that cause vision loss.

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I have been diagnosed with Gilbert's syndrome.

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I am not pregnant or breastfeeding.

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I have had serious heart issues or procedures in the last 6 months.

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My high blood pressure is not controlled despite taking medication.

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I have a muscle disorder that causes high levels of an enzyme in my blood.

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I had major surgery less than 3 weeks ago or am still recovering from it.

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I have been treated with a MEK inhibitor before.

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I have brain metastasis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Best Response Rate (phase II portion)

maximum tolerated dose (MTD) (phase 1b portion)

Secondary study objectives

Progression Free Survival (PFS)

RR by CHOI criteria (phase II portion)

RR by EORTC criteria

+1 more

Side effects data

From 2024 Phase 3 trial • 921 Patients • NCT01909453

41%

Nausea

36%

Diarrhoea

30%

Vomiting

28%

Fatigue

26%

Arthralgia

23%

Blood creatine phosphokinase increased

22%

Constipation

21%

Headache

18%

Asthenia

16%

Abdominal pain

16%

Vision blurred

16%

Pyrexia

15%

Gamma-glutamyltransferase increased

15%

Anaemia

14%

Alopecia

14%

Rash

14%

Myalgia

14%

Dry skin

14%

Hyperkeratosis

12%

Dizziness

11%

Abdominal pain upper

11%

Alanine aminotransferase increased

11%

Hypertension

11%

Pruritus

10%

Oedema peripheral

10%

Nasopharyngitis

10%

Pain in extremity

Back pain

Insomnia

Palmoplantar keratoderma

Muscle spasms

Blood alkaline phosphatase increased

Cough

Aspartate aminotransferase increased

Decreased appetite

Retinal detachment

Dyspnoea

Upper respiratory tract infection

Visual field defect

Erythema

Palmar-plantar erythrodysaesthesia syndrome

Cataract

Blood creatinine increased

Dry eye

Dyspepsia

Ejection fraction decreased

Musculoskeletal pain

Seborrhoeic keratosis

Macular oedema

Skin papilloma

Paraesthesia

Anxiety

Dysgeusia

Chills

Influenza like illness

Influenza

Keratosis pilaris

Photosensitivity reaction

Folliculitis

Weight decreased

Actinic keratosis

Abdominal Pain

Conjunctivitis

Oropharyngeal pain

General Physical Health Deterioration

Cerebral Haemorrhage

Pulmonary Embolism

Stomatitis

Xerosis

Keratoacanthoma

Melanocytic naevus

Pruritus generalised

Rash generalised

Skin hyperpigmentation

Acute Kidney Injury

Rash maculo-papular

Pneumonia

Myocardial Infarction

Bundle Branch Block Left

Enterocolitis

Jaundice

Encephalitis

Herpes Zoster

Infection

Pyelonephritis

Blood Creatinine Increased

Intervertebral Disc Disorder

Myositis

Metastases To Bone

Metastases To Meninges

Transient Ischaemic Attack

Calculus Urethral

Urinary Tract Disorder

Pleural Effusion

Mediastinal Shift

Deep Vein Thrombosis

Embolism

Skin lesion

Non-Cardiac Chest Pain

Campylobacter Gastroenteritis

Urosepsis

Thrombophlebitis Superficial

Solar dermatitis

Thrombocytopenia

Atrial Fibrillation

Atrioventricular Block First Degree

Chorioretinopathy

Retinal Detachment

Colitis

Gastric Ulcer Haemorrhage

Gastrointestinal Haemorrhage

Inguinal Hernia

Death

Inflammation

Cellulitis

Urinary Tract Infection

Chorioretinitis

Gastroenteritis

Dehydration

Pain In Extremity

Rhabdomyolysis

Intracranial Tumour Haemorrhage

Rectal Adenocarcinoma

Balance Disorder

Cervicobrachial Syndrome

Coma

Dysarthria

Epilepsy

Hemiparesis

Somnolence

Spinal Cord Compression

Syncope

Renal Failure

Renal Impairment

Ureterolithiasis

Blood bilirubin increased

Rash papular

Skin exfoliation

Completed Suicide

Abdominal Pain Upper

Pancreatitis

Subileus

Pain

Erysipelas

Cellulitis Streptococcal

Diverticulitis

Femur Fracture

Overdose

Metastases To Central Nervous System

Hyperkalaemia

Dysphagia

Squamous cell carcinoma

Pancreatitis Acute

Multiple Organ Dysfunction Syndrome

Depression Suicidal

Mental Status Changes

Rectal Haemorrhage

Fracture Pain

Angioedema

100%

80%

60%

40%

20%

Study treatment Arm

Part 1: LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)

Part 1: LGX818 300 mg

Part 1: Vemurafenib 960 mg BID

Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)

Part 2: LGX818 300 mg

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: MEK162 in Combination With Imatinib MesylateExperimental Treatment4 Interventions

Pts will be treated with the combination therapy of MEK162 \& imatinib. The phase Ib portion of the study, pts will receive imatinib at 400 mg once daily \& MEK162 at the standard 3+3 escalation doses. Phase Ib expansion cohort, pts will receive the RP2D: imatinib 400 mg once daily (standard of care first line imatinib dose) \& MEK162 at the RP2D twice daily. The phase II portion of the study, pts will receive imatinib at 400 mg once daily \& MEK162 at the RP2D. The MEK162 RP2D was originally determined based on the phase Ib escalation data \& it was established as 45 mg BID. After the completion of the phase Ib dose expansion \& initiation of phase II, the MEK162 RP2D was reduced to 30 mg BID30 for better long term tolerability. Patient's will now begin MEK162 at the revised RP2D of 30 mg BID. 1 cycle is 28 days. If no progression of the tumor is seen, pts will continue on therapy. Pts who have progression of disease will proceed directly to second line therapy as per standard of care.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

biopsy

2002

Completed Phase 4

~8270

MEK162

2013

Completed Phase 3

~2690