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 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
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. (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
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: | up to 5 years |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Overall Response Rate (ORR) |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | |
Measure: | Duration of response (DOR) |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | |
Measure: | Disease Control Rate (DCR) |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | |
Measure: | Progression Free Survival (PFS) |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | |
Measure: | Overall Survival (OS) - (dose expansion part only) |
Time Frame: | Up to 6 years |
Safety Issue: | |
Description: | |
Measure: | Derived PK parameter (Cmax) for LXH254 & LTT462: |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | |
Measure: | Derived PK parameter (AUC) for LXH254 & LTT462 |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | |
Measure: | Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor samples |
Time Frame: | up to 5 years |
Safety Issue: | |
Description: | |
Measure: | Derived PK parameter (Cmax) for LXH254 & trametinib |
Time Frame: | up to 5 years |
Safety Issue: | |
Description: | |
Measure: | Derived PK parameter (AUC) for LXH254 & trametinib |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | |
Measure: | Derived PK parameter (Cmax) for LXH254 & ribociclib |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | |
Measure: | Derived PK parameter (AUC) for LXH254 & ribociclib |
Time Frame: | Up to 5 years |
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
June 23, 2021