Clinical trial · Interventional
A Phase I Study of Oral LGX818 in Adult Patients With Advanced or Metastatic BRAF Mutant Melanoma
A Phase I, Multicenter, Open-label, Dose-escalation Study of Oral LGX818 in Adult Patients With Locally Advanced or Metastatic BRAF Mutant Melanoma
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
CLGX818X2101 is a first-time in-human, phase I study to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of daily administered LGX818 (daily, twice daily and/or every-other-day), a RAF kinase inhibitor. Patients with locally advanced or metastatic melanoma harboring the BRAF V600 mutation (during dose escalation phase and expansion phase) and patients with metastatic colorectal cancer harboring the BRAF V600 mutation (during the expansion phase) will be enrolled. The study consists of a dose escalation part were cohorts of patients will receive escalating oral doses of LGX818, followed by a safety dose expansion part were patients will be treated with oral dose of LGX818 given at the MTD or RP2D.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Melanoma and Metastatic Colorectal Cancer | — | UNRESOLVED | — |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| LGX818 | Drug | Encorafenib | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- LGX818 - Dose escalation
- interventionNames
- Drug: LGX818
- type
- EXPERIMENTAL
- label
- LGX818 - Dose Expansion at MTD or RP2D
- interventionNames
- Drug: LGX818
Primary outcomes (2)
- measure
- Number of Participants With Dose-Limiting Toxicity (DLT) During Dose Escalation Phase
- timeFrame
- Up to 28 days
- description
- DLT= Adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within first 28 days of treatment with encorafenib and met any of following criteria: \>=grade (G)3 neutropenia or thrombocytopenia for \>7 days; G4 thrombocytopenia; febrile neutropenia; \>=G3 serum creatinine, blood bilirubin; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) and lipase and/or serum amylase (\>=G3 for \> 7 consecutive days or G4); \>=G3 ALT or AST and \>=G2 blood bilirubin; \>=G3 persistent hypertension with more than one drug or more intensive therapy or cardiac disorders or AE excluding on-target side-effect that is manageable; G3 fatigue/asthenia for \>7 consecutive days; \>= G3 vomiting or nausea or diarrhea lasting more than 48 hours despite treatment; \>=G3 pancreatitis, rash/photosensitivity (G3 for \> 7 consecutive days despite skin toxicity treatment or G4); G3 or G4 eye disorders.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: For the dose escalation phase: 1. Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer \[AJCC\]). For the dose expansion phase: (i) Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer \[AJCC\]), or (ii) confirmed diagnosis and non-resectable advanced metastatic colorectal cancer (mCRC) for which no further effective standard therapy exists. 2. Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation. 3. Evidence of measurable disease Exclusion Criteria: 1. Previous therapy with a MEK inhibitor. 2. Symptomatic or untreated leptomeningeal disease. 3. Symptomatic or untreated brain metastasis.Patients previously treated for these conditions that are asymptomatic in the absence of corticosteroid therapy are allowed to enroll. Brain metastasis must be stable with verification by imaging. 4. Known acute or chronic pancreatitis. 5. Clinically significant cardiac disease 6. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LGX818 7. Previous or concurrent malignancy. Exceptions to this exclusion criteria include: adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix, treated curatively and without evidence of recurrence for at least 3 years prior to study entry; or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry. 8. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (\> 5 mIU/mL). 9. History of thromboembolic or cerebrovascular events within the last 6 months Other protocol-defined inclusion/exclusion criteria may apply
References
Publications (0)
Data not yet available