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

NCT ID: NCT02607813

Last Updated: 2022-12-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

142 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-18

Study Completion Date

2022-02-19

Brief Summary

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

Detailed Description

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Conditions

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NSCLC Ovarian Cancer Melanoma Other Solid Tumors

Keywords

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LXH254, CRAF, MAPK, solid tumor, PDR001

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose escalation LXH254

Group Type EXPERIMENTAL

LXH254

Intervention Type DRUG

pan-RAF inhibitor

Dose expansion LXH254: Group 1

Group Type EXPERIMENTAL

LXH254

Intervention Type DRUG

pan-RAF inhibitor

Dose expansion LXH254: Group 2

Group Type EXPERIMENTAL

LXH254

Intervention Type DRUG

pan-RAF inhibitor

Dose expansion LXH254: Group 3

Group Type EXPERIMENTAL

LXH254

Intervention Type DRUG

pan-RAF inhibitor

Dose expansion: LXH254 + PDR001

Group Type EXPERIMENTAL

LXH254

Intervention Type DRUG

pan-RAF inhibitor

PDR001

Intervention Type DRUG

Biological: PDR001 anti-PD1 antibody

Dose escalation LXH254 + PDR001

Group Type EXPERIMENTAL

LXH254

Intervention Type DRUG

pan-RAF inhibitor

PDR001

Intervention Type DRUG

Biological: PDR001 anti-PD1 antibody

Interventions

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LXH254

pan-RAF inhibitor

Intervention Type DRUG

PDR001

Biological: PDR001 anti-PD1 antibody

Intervention Type DRUG

Eligibility Criteria

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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


* 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


* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Massachusetts General Hospital MGH Cancer Center

Boston, Massachusetts, United States

Site Status

Memorial Sloan Kettering Cancer Center SC - LXH254X2101

New York, New York, United States

Site Status

UT M.D Anderson Cancer Center SC - LXH254X2101

Houston, Texas, United States

Site Status

Novartis Investigative Site

Toronto, Ontario, Canada

Site Status

Novartis Investigative Site

Paris, , France

Site Status

Novartis Investigative Site

Toulouse, , France

Site Status

Novartis Investigative Site

Heidelberg, , Germany

Site Status

Novartis Investigative Site

Milan, MI, Italy

Site Status

Novartis Investigative Site

Modena, MO, Italy

Site Status

Novartis Investigative Site

Napoli, , Italy

Site Status

Novartis Investigative Site

Chuo Ku, Tokyo, Japan

Site Status

Novartis Investigative Site

Groningen, , Netherlands

Site Status

Medical Oncology, Erasmus MC

Rotterdam, , Netherlands

Site Status

Novartis Investigative Site

Seoul, , South Korea

Site Status

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Novartis Investigative Site

Zurich, , Switzerland

Site Status

Countries

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United States Canada France Germany Italy Japan Netherlands South Korea Spain Switzerland

Related Links

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Other Identifiers

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2015-003421-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLXH254X2101

Identifier Type: -

Identifier Source: org_study_id