Description:
To characterize safety and tolerability and identify a recommended dose and regimen for the
LXH254 in combination with LTT462 or trametinib or ribociclib.
Title
- Brief Title: A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma
- Official Title: A Phase Ib, Open-label, Multicenter Study of Oral LXH254-centric Combinations in Adult Patients With Advanced or Metastatic KRAS or BRAF Mutant Non-Small Cell Lung Cancer or NRAS Mutant Melanoma
Clinical Trial IDs
- ORG STUDY ID:
CLXH254X2102
- SECONDARY ID:
2016-004293-18
- NCT ID:
NCT02974725
Conditions
- Non-Small Cell Lung Cancer
- Melanoma
Interventions
Drug | Synonyms | Arms |
---|
LXH254 | | LXH254+LTT462 |
LTT462 | | LXH254+LTT462 |
Trametinib | | LXH254+Trametinib |
LXH254 | | LXH254+Trametinib |
Ribociclib | | LXH254+Ribociclib |
Purpose
To characterize safety and tolerability and identify a recommended dose and regimen for the
LXH254 in combination with LTT462 or trametinib or ribociclib.
Trial Arms
Name | Type | Description | Interventions |
---|
LXH254+LTT462 | Experimental | | |
LXH254+Trametinib | Experimental | | |
LXH254+Ribociclib | Experimental | | |
Eligibility Criteria
Inclusion Criteria:
- Patients must have advanced or metastatic NSCLC or melanoma
- Presence of KRAS or BRAF mutation (NSCLC) or NRAS mutation (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
Exclusion Criteria:
- Dose expansion - KRAS or NRAS mutant patients groups: Prior treatment with a RAFi
(including any BRAFi and pan-RAFi), MEKi and/or ERKi. BRAF mutant patients group:
Prior treatment with an ERKi and/or a pan-RAFi.
- 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of participants with Adverse Events (AEs) as a measure of safety and tolerability |
Time Frame: | 12 months |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Overall Response Rate (ORR) |
Time Frame: | Up to 12 months |
Safety Issue: | |
Description: | |
Measure: | Duration of response (DOR) |
Time Frame: | Up to 12 months |
Safety Issue: | |
Description: | |
Measure: | Disease Control Rate (DCR) |
Time Frame: | Up to 12 months |
Safety Issue: | |
Description: | |
Measure: | Progression Free Survival (PFS) |
Time Frame: | Up to 12 months |
Safety Issue: | |
Description: | |
Measure: | Overall Survival (OS) - (dose expansion part only) |
Time Frame: | Up to 12 months |
Safety Issue: | |
Description: | |
Measure: | Plasma concentrations of LXH254 |
Time Frame: | Up to Month 5 |
Safety Issue: | |
Description: | |
Measure: | Plasma concentrations of LTT462 |
Time Frame: | Up to Month 5 |
Safety Issue: | |
Description: | |
Measure: | Derived PK parameter (Cmax) for LXH254 & LTT462: |
Time Frame: | Up to Month 5 |
Safety Issue: | |
Description: | |
Measure: | Derived PK parameter (AUC) for LXH254 & LTT462 |
Time Frame: | Up to Month 5 |
Safety Issue: | |
Description: | |
Measure: | Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor samples |
Time Frame: | baseline, month 12 |
Safety Issue: | |
Description: | |
Measure: | Plasma concentrations of trametinib |
Time Frame: | Up to Month 5 |
Safety Issue: | |
Description: | |
Measure: | Derived PK parameter (Cmax) for LXH254 & trametinib |
Time Frame: | Up to Month 5 |
Safety Issue: | |
Description: | |
Measure: | Derived PK parameter (AUC) for LXH254 & trametinib |
Time Frame: | Up to Month 5 |
Safety Issue: | |
Description: | |
Measure: | Plasma concentrations of ribociclib |
Time Frame: | Up to Month 5 |
Safety Issue: | |
Description: | |
Measure: | Derived PK parameter (Cmax) for LXH254 & ribociclib |
Time Frame: | Up to Month 5 |
Safety Issue: | |
Description: | |
Measure: | Derived PK parameter (AUC) for LXH254 & ribociclib |
Time Frame: | Up to Month 5 |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- NSCLC
- Melanoma
- NRAS
- KRAS
- BRAF
- LXH254
- LTT462
- Trametinib
- Ribocliclib
- Non-small cell lung carcinoma (NSCLC)
- treatment of lung cancer after first metastasis
- lung cancer
- lung adenocarcinoma
- Large-cell lung carcinoma
- Non small cell lung carcinoma
- Non small cell lung cancer
- Large cell lung carcinoma
- Large cell lung cancer
- squamous cell lung carcinoma
Last Updated
January 17, 2020