A phase II, multi-center, open-label study of sequential LGX818/MEK162 combination followed by a rational combination with targeted agents after progression, to overcome resistance in adult patients with locally advanced or metastatic BRAF V600 melanoma
- Conditions
- melanomaskin cancer10040900
- Registration Number
- NL-OMON45032
- Lead Sponsor
- Array Biopharma
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 15
1. Age >= 18 years at the start of dosing
2. Histologically confirmed diagnosis of unresectable stage III or metastatic melanoma (stage IIIC to IV per American Joint Committee on Cancer [AJCC]).
3. Documented evidence of BRAF V600 mutation
4. Evidence of measurable disease, as determined by RECIST v1.1.
5. ECOG Performance Status <= 2.
6. Negative serum pregnancy test within 72 hours prior to the first dose of study treatment in all women of childbearing potential.
7. For Group A only: patients who are naïve to selective BRAF and MEK inhibitors and might have received other allowed treatments
8. For Group A only: Patients must provide either archival or newly obtained tumor sample at baseline. In addition, patients must agree to a mandatory biopsy at the time of progression from LGX818/MEK162 combination, if not medically contraindicated.
9. For Group B only: Patients with progressive disease following any single or double-agent BRAF and MEK inhibitors other than LGX818/MEK162
10. For Group B only: The most recent biopsy sample collected after progression from any BRAF and/or MEK inhibitor (other than LGX818 and MEK162 combination) must be available before entering the Run-in. In addition, patients must agree to a biopsy at the time of progression from LGX818/MEK162 combination if necessary and not medically contraindicated.
11. For Group C only Progressive disease documented per RECIST v 1.1 and determined using radiological assessments, following prior treatment with LGX818/MEK162 combination.
12. For Group C only A pre-LGX818/MEK162 combination archival tumor sample must be available.
13. For Group C only A biopsy sample at disease progression, post-LGX818/MEK162 combination, must be either already available from previous studies or collectable at screening/baseline of this study..
14 Able to understand and voluntarily sign the informed consent form prior to any screening procedure, and ability to comply with the study visit schedule and other protocol requirements.
15. For Group B only: Patients who progressed after treatment with single agent BRAF or MEK inhibitor or the combination of BRAF/MEK inhibitors (excluding LGX818/MEK162 combination) and patients who did not progress on their prior BRAF and/or MEK inhibitor regimen (including LGX818 and/or MEK162 inhibitor), but did not tolerate this treatment, may enter the Run-in (Group B) upon consultation with Sponsor.
Part I and Run-in
1. Symptomatic or untreated leptomeningeal disease.
2. Symptomatic brain metastasis.
3. Known acute or chronic pancreatitis.
4. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO
5 Patients who have undergone any major surgery within the last 2 weeks prior to starting study drug or who would not have fully recovered from previous surgery.;PART II
Patients are NOT eligible for enrollment in Part II of this study if they meet any exclusion criteria listed above, and all the applicable additional exclusion criteria listed below.
1. Patients who discontinued LGX818/MEK162 for more than 6 weeks prior to the scheduled first dose of triple combination (Part II), and AEs related to the above treatment are not resolved to at least grade 2.;Additional Exclusion Criteria for Part II for selected triple combination may apply. Please refer to the protocol.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Overall response rate (ORR) of LGX818/MEK162 in combination with third targeted<br /><br>agents after progression on LGX818/MEK162 combination therapy.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 of Combination Part<br /><br>(Part II)<br /><br><br /><br>Adverse Events (AEs), serious AEs (SAEs), changes in hematology and chemistry<br /><br>values, vital signs, electrocardiograms (ECGs), dose interruptions, reductions<br /><br>and dose intensity.</p><br>