A Phase Ib/II study of LGX818 in combination with MEK162 in adult patients with BRAF dependent advanced solid tumors

• Register: EUCTR
• Last refreshed on: 21 September 2015
• Main ID: EUCTR2011-005875-17-FR
• Date of registration: 16/09/2015
• Prospective Registration: No
• Primary sponsor: Novartis Pharma Services AG
• Public title: A Phase Ib/II study of LGX818 in combination with MEK162 in adult patients with BRAF dependent advanced solid tumors
• Scientific title: A Phase Ib/II, multicenter, open-label, dose escalation study of LGX818 in combination with MEK162 in adult patients with BRAF V600 - dependent advanced solid tumors
• Date of first enrolment: 13/11/2013
• Target sample size: 127
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-005875-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Australia, Belgium, Canada, France, Italy, Singapore, Spain, Switzerland, United States

Contacts

• Name: Information communication médicales
• Affiliation: Novartis Pharma S.A.S.

• Name: Information communication médicales
• Affiliation: Novartis Pharma S.A.S.

Key inclusion & exclusion criteria

Inclusion criteria:
• Age = 18 years for both phases and arms
• Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]), or confirmed diagnosis of non-resectable advanced metastatic colorectal cancer (mCRC), or any other indication upon agreement with the Sponsor, whose disease has progressed despite previous antineoplastic therapy or for whom no further effective standard therapy is available.
• Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation.
• Evidence of measurable disease as determined by RECIST v1.1.
• World Health Organization (WHO) Performance Status = 2.
• Negative serum pregnancy test within 72 hours prior to the first study
dose in all women of childbearing potential.
• for phase II : availability of a tumor biopsy
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 114
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13

Exclusion criteria:
• Progressive disease following prior treatment with RAF-inhibitors in combination with MEK-inhibitors.
• Symptomatic or untreated leptomeningeal disease.
• Symptomatic brain metastases. Patients are not permitted to receive enzyme inducing anti-epileptic drugs.
• Known acute or chronic pancreatitis.
• History or current evidence of retinal disease, retinal vein occlusion or ophthalmopathy.
• Clinically significant cardiac disease.
• Patients with abnormal laboratory values at Screening/baseline.
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LGX818/MEK162
• Previous or concurrent malignancy.
• Pregnant or nursing (lactating) women.
Other protocol-defined exclusion criteria may apply.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with solid tumors harboring a BRAF V600 mutation.

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Code: LGX818
Pharmaceutical Form: Capsule, hard
Current Sponsor code: LGX818
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Product Code: MEK162
Pharmaceutical Form: Film-coated tablet
CAS Number: 606143-89-9
Current Sponsor code: MEK162
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-

Product Code: LGX818
Pharmaceutical Form: Capsule, hard
Current Sponsor code: LGX818
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Product Code: LGX818
Pharmaceutical Form: Capsule, hard
Current Sponsor code: LGX818
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Code: LGX818
Pharmaceutical Form: Capsule, hard
Current Sponsor code: LGX818
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Main Objective: Phase Ib: To estimate the MTD(s) and/or RP2D(s) of oral LGX818 in combination with oral MEK162 in patients with BRAF V600-dependent advanced solid tumors.
Phase II: To assess clinical efficacy of the LGX818 and MEK162 combination in the Phase II populations.

Timepoint(s) of evaluation of this end point: Phase Ib : up to 8 months
Phase II : up to 14 months

Primary end point(s): Phase Ib: Incidence of Dose Limiting Toxicities

Phase II : Disease control rate (DCR) as per RECIST v1.1 OR Objective Response Rate (ORR) as per RECIST v1.1 (depending on arm)

Secondary Objective: 1. Phase Ib and II : to characterize the safety and tolerability of LGX818 and MEK162 in combination.
2. Phase Ib : to determine the single and multiple dose PK profile of the LGX818 and MEK162 combination.
3. Phase Ib : to assess preliminary anti-tumor activity of the LGX818 and MEK162 combination.
4. Phase II : to further assess clinical efficacy of the LGX818 and MEK162 combination in the Phase II populations and to characterize baseline molecular status of molecules relevant to RAF/MEK/ERK and
EGFR/PI3K/AKT signaling in tumor tissue.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. up to 17 months
2. up to 8 months
3. up to 8 months
4. up to 14 months

Secondary end point(s): 1. Phase Ib and II : Incidence and severity (as per CTCAE grading) of AEs.
2. Phase Ib : Plasma concentrations of MEK162 and LGX818 respectively at different timepoints prior and post study drug combination dosing on several days within Cycle 1 and subsequent cycles.
3. Phase Ib : ORR as per RECIST v1.1
4. Phase II : Progression Free Survival (PFS) as per RECIST 1.1 in all patients with the same indication
5. Baseline molecular status (mutation/amplification/expression) in tumor tissue of potential predictive markers of tumor response or resistance (BRAF, HRAS, KRAS, NRAS, PTEN, cKIT, PIK3CA, MAP2K1, MAP2K2, ARAF, c-MET, RAF1, EGFR).

Secondary ID(s)

2011-005875-17-ES

CMEK162X2110

Source(s) of Monetary Support

Novartis Pharma Services AG