Phase I Study of LXH254 in Patients With Advanced Solid Tumors Haboring MAPK Pathway Alterations

Ovarian Cancer Clinical Trial

Official title:

A Phase I Dose Finding Study of Oral LXH254 in Adult Patients With Advanced Solid Tumors Harboring MAPK Pathway Alterations

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02607813
• Other study ID #: CLXH254X2101
• Secondary ID: 2015-003421-33
• Status: Terminated
• Phase: Phase 1
• 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
• 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.

Related Conditions & MeSH terms

• Melanoma
• NSCLC
• Other Solid Tumors
• Ovarian Cancer

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

External Links

•   Study Results