A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma
- Conditions
- Non-Small Cell Lung CancerMelanoma
- Interventions
- Registration Number
- NCT02974725
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
To characterize safety and tolerability and identify a recommended dose and regimen for the LXH254 in combination with LTT462 or trametinib or ribociclib.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 241
- Patients must have advanced or metastatic NSCLC or cutaneous melanoma
- Presence of KRAS or BRAF mutation (NSCLC) or NRAS mutation (cutaneous melanoma) in tumor tissue
- All patients participating in this clinical trial must have progressed following standard therapy or, in the opinion of the Investigator, no effective standard therapy exists, is tolerated, appropriate or is considered equivalent to study treatment.
- ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2
-Dose expansion - KRAS or NRAS mutant patients groups: Prior treatment with a RAFi (including any BRAFi and pan-RAFi), MEKi and/or ERKi. (Patients with KRAS mutant NSCLC with prior G12C inhibitor treatments are also excluded in the LXH254+trametinib expansion part). BRAF mutant patients group: Prior treatment with any EGFR, ALK, ROS1, KRAS, RAF (both BRAFV600 selective and pan-RAF), MEK1/2 and/or ERK1/2 inhibitors (for patients with BRAF V600 mutant NSCLC, prior treatments with BRAF and MEK1/2 inhibitors are allowed).
Patients who have received more than 3 lines of anti-cancer therapy are excluded.
- 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 (PPI) which cannot be discontinued 3 days prior to the start study treatment and for the duration of the study.
- Patients with Gilbert's syndrome or other heritable diseases of bile processing.
Other protocol-defined inclusion/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description LXH254+LTT462 LTT462 - LXH254+LTT462 LXH254 - LXH254+Ribociclib LXH254 - LXH254+Trametinib LXH254 - LXH254+Trametinib Trametinib - LXH254+Ribociclib Ribociclib -
- Primary Outcome Measures
Name Time Method Tolerability measured by the number of subjects who have interruptions/reductions of study treatment and reason for interruptions/reductions up to 5 years Number of participants with Adverse Events (AEs) as a measure of safety and tolerability up to 5 years Dose limiting toxicities (DLTs) (dose escalation only) up to 3 years Tolerability measured by the dose intensity of study drug, Relative Dose intensity for subjects with non-zero duration of exposure is computed as the ratio of dose intensity and planned dose intentity Up to 5 years
- Secondary Outcome Measures
Name Time Method Derived PK parameter (AUC) for LXH254 & ribociclib Up to 5 years Overall Response Rate (ORR) Up to 5 years Progression Free Survival (PFS) Up to 5 years Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor samples up to 5 years Duration of response (DOR) Up to 5 years Derived PK parameter (AUC) for LXH254 & LTT462 Up to 5 years Disease Control Rate (DCR) Up to 5 years Overall Survival (OS) - (dose expansion part only) Up to 5 years Derived PK parameter (Cmax) for LXH254 & LTT462: Up to 5 years Derived PK parameter (AUC) for LXH254 & trametinib Up to 5 years Derived PK parameter (Cmax) for LXH254 & trametinib up to 5 years Derived PK parameter (Cmax) for LXH254 & ribociclib Up to 5 years
Trial Locations
- Locations (7)
Novartis Investigative Site
🇸🇪Stockholm, Sweden
Uni of TX MD Anderson Cancer Cntr
🇺🇸Houston, Texas, United States
Sarah Cannon Research Institute Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
University of California San Diego .
🇺🇸San Diego, California, United States
UCSF Medical Center
🇺🇸San Francisco, California, United States
Massachusetts General Hospital SC
🇺🇸Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Ctr .
🇺🇸New York, New York, United States