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

Phase 1TerminatedNCT02607813

Novartis Pharmaceuticals142 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

142

Conditions

NSCLC Ovarian Cancer Melanoma Other Solid Tumors

Interventions

LXH254DRUG

pan-RAF inhibitor

PDR001DRUG

Biological: PDR001 anti-PD1 antibody

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (18)

Massachusetts General Hospital MGH Cancer Center

Boston, Massachusetts, United States

Memorial Sloan Kettering Cancer Center SC - LXH254X2101

New York, New York, United States

Outcomes

Primary Outcomes

Safety and tolerability as assessed by incidence and severity of adverse events (AEs), dose interruptions, reductions, and dose intensity.

cycle = 28 days

Time frame: 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)

Incidence and nature of dose limiting toxicities (DLTs) (dose escalation and LXH254 single agent only)

cycle = 28 days

Time frame: 28 days

Incidence and nature of dose limiting toxicities (DLTs) (dose escalation and LXH254 in combination with PDR001 only)

cycle =28 days

Time frame: 56 days

Secondary Outcomes

Overall response rate (ORR)

cycle = 28 days

Time frame: Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months

Disease control rate (DCR)

cycle = 28 days

Time frame: Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months

Duration of response (DoR)

cycle = 28 days

Time frame: Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months

Progression-free survival (PFS)

cycle = 28 days

Time frame: Every 2 cycles after starting study treatment until disease progression; expected duration approximately 12 months

Data from ClinicalTrials.gov

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