GX818/MEK162 Combination With Agents (BKM120; LEE011; BGJ398; INC280) in Advanced BRAF Melanoma

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 140

Inclusion Criteria

- Patients (males and females) age = 18 years
- Histologically confirmed diagnosis of unresectable stage III or metastatic melanoma (stage IIIC to IV per American Joint Committee on Cancer [AJCC])
- Documented evidence of BRAF V600 mutation.
- Evidence of measurable disease, as determined by RECIST v1.1.

Inclusion criteria for triple combinations:
- Progressive disease following prior treatment with LGX818/MEK162 combination.
- A pre-LGX818/MEK162 combination archival tumor sample must be available

Other protocol-defined inclusion criteria may apply
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 112
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 28

Exclusion Criteria

Patients eligible for Part I or Run-in of this study must NOT meet any of the following criteria:
1. Symptomatic or untreated leptomeningeal disease.
2. Symptomatic brain metastasis.
3. Patients are not permitted to receive enzyme inducing anti-epileptic drugs.
4. Known acute or chronic pancreatitis.
5. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO
6. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drugs (e.g., ulcerative
diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).
7. Patients treated with warfarin or other coumadin derived anti coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed.
8. Previous or concurrent malignancy. Exceptions: 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 first dose administration.
9. 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 serum hCG laboratory test. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, are not allowed to participate in this study UNLESS they are using highly effective methods of contraception throughout the study and for 3 months after study drug discontinuation.
10. Sexually active males must use a condom during intercourse while taking the drug and for 3 months after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
Enrollment in Part II
As of Protocol Amendment 06, enrollment to the BKM120-, BGJ398- and
INC280-containing arms in Part II is closed. Therefore, in Part II, patients who are eligible may only enroll in the LGX818/MEK162 + LEE011 arm.
11. 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.
- LGX818/MEK162 + INC280: This arm is closed to enrollment as this combination is no longer being explored (Amendment 06).
12. Patients unable to stop known CYP3A4, CYP1A2, CYP2C8 or CYP2C19 substrates with narrow therapeutic index. These medications should be stopped 7 days prior to first dose of study treatment (refer to Section 6.4.3 and
Appendix 7 for prohibited medications for this combination treatment).
13. Patients receiving treatment with long acting proton pump inhibitors, and unable to discontinue them 3 days prior to the start of study
treatment and during the course of the study.
14. Asymptomatic serum amylase > CTCAE Grade 2 (1.5-2.0xULN). Patients with Grade 1 or Grade 2 serum amylase at the beginning of the
study must be confirmed to have no signs or symptoms suggesting pancreatitis or pancreatic injury (e.g., elevated P-amylase, abnormal imaging findings of pancreas, etc.)
- LGX818/MEK162 + BGJ398: This arm is closed to enrollment as this combination is no longer being explored (Amendment 06)
15. History and/or

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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