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

Novartis

Status and phase: Terminated; Phase 1

Conditions: Other Solid Tumors; Melanoma; Ovarian Cancer; NSCLC

Treatments: Drug: PDR001; Drug: LXH254

Study type: Interventional

Funder types: Industry

Identifiers

NCT02607813

CLXH254X2101

2015-003421-33 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment: 142 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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142 participants in 6 patient groups

Dose escalation LXH254

Experimental group

Treatment:

Drug: LXH254

Dose expansion LXH254: Group 1

Experimental group

Treatment:

Drug: LXH254

Dose expansion LXH254: Group 2

Experimental group

Treatment:

Drug: LXH254

Dose expansion LXH254: Group 3

Experimental group

Treatment:

Drug: LXH254

Dose expansion: LXH254 + PDR001

Experimental group

Treatment:

Drug: LXH254

Drug: PDR001

Dose escalation LXH254 + PDR001

Experimental group

Treatment:

Drug: LXH254

Drug: PDR001