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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02607813
Other study ID # CLXH254X2101
Secondary ID 2015-003421-33
Status Terminated
Phase Phase 1
First received
Last updated
Start date January 18, 2016
Est. completion date February 19, 2022

Study information

Verified date March 2022
Source Novartis
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

A Phase I Study of LXH254 in Patients With Advanced Solid Tumors That Harbor MAPK Pathway Alterations.


Recruitment information / eligibility

Status Terminated
Enrollment 142
Est. completion date February 19, 2022
Est. primary completion date February 18, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - All patients participating in this clinical trial must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or appropriate. - Eastern Cooperative Oncology Group (ECOG) performance status = 1 - Presence of at least one measurable lesion according to RECIST v1.1. - Documented MAPK alteration Additional inclusion criteria for the Dose Expansion part: LXH254 in combination with PDR001: - Patients with confirmed KRAS-mutated NSCLC - Patients with confirmed NRAS-mutated melanoma (cutaneous melanoma only) Exclusion Criteria: - Prior treatment with a BRAFi, MEKi and/or pan-RAF inihibitors for patients to be enrolled in the dose expansion part. Exceptions may be made after documented agreement between Novartis and Investigator. - History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO. - Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures. - Patients receiving proton pump inhibitors which cannot be discontinued 3 days prior to the start study treatment and for the duration of the study. - Pregnant or nursing (lactating) women Additional exclusion criteria for LXH254 in combination with PDR001 - History of severe hypersensitivity reactions, which in the opinion of the investigator may cause in increased risk of serious infusion reaction. - Known human immunodeficiency virus (HIV). - Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection. - Active, known or suspected autoimmune disease. - Active infection requiring systemic antibiotic therapy - Patients requiring systemic steroid therapy or any immunosuppressive therapy (=10mg/day prednisone or equivalent) which cannot be discontinued at least 7 days prior to first dose of study treatment. - Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment. Other inclusion/exclusion criteria as per protocol may apply.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
LXH254
pan-RAF inhibitor
PDR001
Biological: PDR001 anti-PD1 antibody

Locations

Country Name City State
Canada Novartis Investigative Site Toronto Ontario
France Novartis Investigative Site Paris Cedex 10
France Novartis Investigative Site Toulouse
Germany Novartis Investigative Site Heidelberg
Italy Novartis Investigative Site Milano MI
Italy Novartis Investigative Site Modena MO
Italy Novartis Investigative Site Napoli
Japan Novartis Investigative Site Chuo ku Tokyo
Korea, Republic of Novartis Investigative Site Seoul
Netherlands Novartis Investigative Site Groningen
Netherlands Medical Oncology, Erasmus MC Rotterdam
Spain Novartis Investigative Site Barcelona Catalunya
Spain Novartis Investigative Site Madrid
Spain Novartis Investigative Site Madrid
Switzerland Novartis Investigative Site Zuerich
United States Massachusetts General Hospital MGH Cancer Center Boston Massachusetts
United States UT M.D Anderson Cancer Center SC - LXH254X2101 Houston Texas
United States Memorial Sloan Kettering Cancer Center SC - LXH254X2101 New York New York

Sponsors (1)

Lead Sponsor Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Spain,  Switzerland, 

Outcome

Type Measure Description Time frame Safety issue
Primary Safety and tolerability as assessed by incidence and severity of adverse events (AEs), dose interruptions, reductions, and dose intensity. cycle = 28 days From Cycle 1 Day 1 until 30 days for LXH254 single agent and 150 days for LXH254 in combination with PDR001 post study treatment (expected duration approximately 12 months)
Primary Incidence and nature of dose limiting toxicities (DLTs) (dose escalation and LXH254 single agent only) cycle = 28 days 28 days
Primary Incidence and nature of dose limiting toxicities (DLTs) (dose escalation and LXH254 in combination with PDR001 only) cycle =28 days 56 days
Secondary Overall response rate (ORR) cycle = 28 days Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months
Secondary Disease control rate (DCR) cycle = 28 days Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months
Secondary Duration of response (DoR) cycle = 28 days Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months
Secondary Progression-free survival (PFS) cycle = 28 days Every 2 cycles after starting study treatment until disease progression; expected duration approximately 12 months
Secondary Overall survival (OS) - only for dose expansion cycle = 28 days From time of start treatment until the date of death; expected duration approximately 12 months
Secondary Plasma concentrations of LXH254 cycle = 28 days Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Secondary Derived PK parameters of LXH254: Area Under the Curve (AUC) cycle = 28 days Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Secondary Derived PK parameters of LXH254: Peak Plasma Concentration (Cmax) cycle = 28 days Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Secondary Derived PK parameters of LXH254: Time to Peak Plasma Concentration (Tmax) cycle = 28 days Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Secondary Derived PK parameters of LXH254: half-life (T1/2) cycle = 28 days Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Secondary Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor tissue and in blood cycle = 28 days Cycle 1 day 1, 2, 3, 15, and 16; upon disease progression (expected duration approximately 12 months)
Secondary Plasma concentrations of PDR001 cycle = 28 days Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1
Secondary Derived PK parameters of PDR001: Area Under the Curve (AUC) cycle = 28 days Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1
Secondary Derived PK parameters of PDR001: Peak Plasma Concentration (Cmax) cycle = 28 days Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1
Secondary Derived PK parameters of PDR001: Time to Peak Plasma Concentration (Tmax) cycle = 28 days Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1
Secondary Derived PK parameters of PDR001: half-life (T1/2) cycle = 28 days Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1
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