A phase I dose finding study of oral LXH254 in adult patients with advanced solid tumors harboring MAPK pathway alterations

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

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.