advanced solid tumors harboring MAPK pathway alterations
Conditions
Interventions
LXH254 single agent (single agent arm), LXH254 in combination with PDR001 (combination arm).
Sponsors
Novartis Pharma. K.K.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent must be obtained prior to any study specific procedures. 2. Patient (male or female) >= 18 years of age. 3. 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. 4. Eastern Cooperative Oncology Group (ECOG) performance status =< 1. 5. Patients must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to treating institution's own guidelines and requirements for such procedure. 6. Presence of at least one measurable lesion according to RECIST (Response Evaluation Criteria in Solid Tumors) v1.1. 7. Dose escalation part:Patients must have advanced solid tumors harboring at least one MAPK pathway alteration when enrolled in cohorts testing LXH254 single agent or NSCLC harboring KRAS mutations and NRAS-mutated melanoma for cohorts testing LXH254 in combination with PDR001. Dose expansion part: LXH254 in combination with PDR001 1) Patients with confirmed KRAS-mutated NSCLC. 2) Patients with confirmed NRAS-mutated melanoma.
Exclusion criteria
Exclusion criteria: 1. Prior treatment with a BRAFi, MEKi and/or pan-RAFi in patients enrolled in dose expansion part. Exceptions may be made after documented agreement between Novartis and Investigator. 2. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO. 3. Patients receiving proton pump inhibitors which cannot be discontinued 3 days prior to the start study treatment and for the duration of the study. 4. For patients treated with LXH254 single agent in the dose expansion part and all patients treated with LXH254 in combination with PDR001: Use of any immunotherapy including PD-1- or PD-L1-directed therapy must have ended at least 6 weeks prior to first dose of study treatment. 5. History of severe hypersensitivity reactions, which in the opinion of the investigator may cause in increased risk of serious infusion reaction.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety To characterize safety and tolerability of LXH254 single agent and identify a recommended dose and regimen for future studies in adult patients with advanced solid tumors harboring MAPK pathway alterations. To characterize safety and tolerability of LXH254 in combination with PDR001 and identify a recommended dose and regimen for future studies in adult patients with KRAS-mutant NSCLC and NRAS-mutated melanoma patients. | — |
Countries
Asia except Japan, Europe, Japan, North America, Oceania, South America
Contacts
Public ContactTakamitsu Hirano
Novartis Pharma. K.K.
Outcome results
None listed