Description:
The primary purpose of this study is to evaluate the efficacy of LXH254 combinations in
previously treated unresectable or metastatic melanoma
Title
- Brief Title: Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma
- Official Title: A Randomized, Open-label, Multi-arm, Two-part, Phase II Study to Assess Efficacy and Safety of Multiple LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic BRAFV600 or NRAS Mutant Melanoma
Clinical Trial IDs
- ORG STUDY ID:
CLXH254C12201
- NCT ID:
NCT04417621
Conditions
Interventions
Drug | Synonyms | Arms |
---|
LXH254 | | LXH254 + LTT462 |
LTT462 | | LXH254 + LTT462 |
Trametinib | | LXH254 + trametinib |
Ribociclib | | LXH254 + ribociclib |
Purpose
The primary purpose of this study is to evaluate the efficacy of LXH254 combinations in
previously treated unresectable or metastatic melanoma
Trial Arms
Name | Type | Description | Interventions |
---|
LXH254 + LTT462 | Experimental | | |
LXH254 + trametinib | Experimental | | |
LXH254 + ribociclib | Experimental | | |
Eligibility Criteria
Inclusion Criteria:
Male or female must be ≥ 12 years For adolescents only (12-17 years): body weight > 40kg
Histologically confirmed unresectable or metastatic cutaneous melanoma
Previously treated for unresectable or metastatic melanoma:
- Participants with NRAS mutation:
- Participants must have received prior systemic therapy for unresectable or metastatic
melanoma with an anti-PD-1/PD-L1 checkpoint inhibitor as a single agent or in
combination with anti-CTLA-4. No additional systemic treatment is allowed for
unresectable or metastatic melanoma
- A maximum of two prior lines of systemic immunotherapy for unresectable or metastatic
melanoma are allowed
- The last dose of prior therapy (anti-PD-1, anti-PD-L1 or anti-CTLA-4) must have been
received more than four weeks before randomization
- Participants must have documented confirmed progressive disease as per RECIST v1.1
while on/after treatment with checkpoint inhibitor therapy. The last progression must
have occurred within 12 weeks prior to randomization in the study
- Participants with BRAFV600 mutant disease:
- Participants must have received prior systemic therapy for unresectable or metastatic
melanoma with anti-PD-1/PD-L1 as a single agent or in combination with anti-CTLA-4.
Additionally, participants must have received targeted therapy with a RAFi as a single
agent or in combination with a MEKi as the last prior therapy. No additional systemic
treatment is allowed for advanced or metastatic melanoma
- A maximum of three prior lines of systemic therapy for unresectable or metastatic
melanoma are allowed
- The last dose of targeted therapy (last prior therapy) must have been received more
than 2 weeks prior to randomization
- Participants must have documented progressive disease as per RECIST v1.1 while
on/after treatment with targeted therapy. The last progression must have occurred
within 12 weeks prior to randomization in the study Other protocol-defined inclusion
criteria may apply.
Exclusion Criteria:
Treatment with any of the following anti-cancer therapies prior to the first dose of study
treatment within the stated timeframes:
- ≤ 4 weeks for radiation therapy or ≤ 2 weeks for limited field radiation for
palliation prior to the first dose of study treatment.
- ≤ 4 weeks or ≤ 5 half-life (whichever is shorter) for small molecule therapeutics.
- ≤ 4 weeks for any immunotherapy treatment including immune checkpoint inhibitors.
Participants participating in additional parallel investigational drug or medical device
studies.
All primary central nervous system (CNS) tumors or symptomatic CNS metastases that are
neurologically unstable History or current evidence of retinal vein occlusion (RVO) or
current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of
hyperviscosity or hypercoagulability syndromes).
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.
Other protocol-defined exclusion criteria may apply
Maximum Eligible Age: | 120 Years |
Minimum Eligible Age: | 12 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Overall Response Rate |
Time Frame: | 35 months |
Safety Issue: | |
Description: | Confirmed ORR using RECIST v1.1, per local assessment |
Secondary Outcome Measures
Measure: | Duration of Reposnse (DOR) |
Time Frame: | 4 years |
Safety Issue: | |
Description: | Local and central assessment |
Measure: | Progression Free Survival (PFS) |
Time Frame: | 4 years |
Safety Issue: | |
Description: | |
Measure: | Disease Control Rate (DCR) |
Time Frame: | 3 years |
Safety Issue: | |
Description: | Using RECIST v1.1, per local and central assessment |
Measure: | Overall Survival (OS) |
Time Frame: | 4 years |
Safety Issue: | |
Description: | |
Measure: | Derived PK parameter (Cmax) for LXH254 & LTT462 |
Time Frame: | Up to 5 months |
Safety Issue: | |
Description: | |
Measure: | Derived PK parameter (Cmax) for LXH254 & trametinib |
Time Frame: | Up to 5 months |
Safety Issue: | |
Description: | |
Measure: | Derived PK parameter (Cmax) for LXH254 & ribociclib |
Time Frame: | Up to 5 months |
Safety Issue: | |
Description: | |
Measure: | Derived PK parameter (AUC) for LXH254 & LTT462 |
Time Frame: | Up to 5 months |
Safety Issue: | |
Description: | |
Measure: | Derived PK parameter (AUC) for LXH254 & trametinib |
Time Frame: | Up to 5 months |
Safety Issue: | |
Description: | |
Measure: | Derived PK parameter (AUC) for LXH254 & ribociclib |
Time Frame: | Up to 5 months |
Safety Issue: | |
Description: | |
Measure: | Incidence of adverse events (AEs) and serious adverse events (SAEs) |
Time Frame: | 35 months |
Safety Issue: | |
Description: | Number of participants with Adverse Events (AEs) and SAEs as a measure of safety and tolerability |
Measure: | Dose Interruptions |
Time Frame: | 35 months |
Safety Issue: | |
Description: | Tolerability measured by the number of subjects who have interruptions of study treatment and reason for interruptions |
Measure: | Dose reductions |
Time Frame: | 35 months |
Safety Issue: | |
Description: | Tolerability measured by the number of subjects who have reductions of study treatment and reason for reductions |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- LXH254
- Melanoma
- NRAS
- BRAF
- LTT462
- Trametinib
- Ribocliclib
Last Updated
July 19, 2021