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

Phase 1

• Conditions: Patients with solid tumors harboring a BRAF V600 mutation.; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-005875-17-BE
• Lead Sponsor: Array BioPharma Inc. (a wholly owned subsidiary of Pfizer Inc)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-10-24
• Last Update Posted: 5 July 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 179

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.
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 161
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18

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. For the triple combination :
patients presenting any brain metastases are excluded.
• 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. For
the triple combination : patients with abnormal coagulation evaluations
(PT/INR >1.5 x ULN or aPTT >1.5 x ULN) are excluded.
• 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.
• For addition of LEE011 in the triple combination, congenital long QT
syndrome or family history of unexpected sudden cardiac death and/or
hypokalemia CTCAE Grade = 3.
Other protocol-defined exclusion criteria may apply.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified