Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma

Melanoma Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04417621
• Other study ID #: CLXH254C12201
• Secondary ID: 2020-000873-26
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 30, 2020
• Est. completion date: September 30, 2024

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of this study is to evaluate the efficacy of LXH254 combinations in previously treated unresectable or metastatic melanoma

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 134
• Est. completion date: September 30, 2024
• Est. primary completion date: August 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 120 Years

Eligibility

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 checkpoint inhibitors (CPI), either an anti-PD-1/PD-L1 as a single agent or in combination with anti-CTLA-4, investigational agents, chemotherapy or locally directed anti-neoplastic agents.
• A maximum of two prior lines of systemic CPI-containing immunotherapy for unresectable or metastatic melanoma are allowed. Additional agents administered with CPI are permitted.
• To rule out pseudo-progression, participants must have documented confirmed progressive disease as per RECIST v1.1 while on/after treatment with checkpoint inhibitor therapy. Confirmation is not required for patients who remained on treatment for >6 months.
• Participants with BRAFV600 mutant disease:
• Participants must have received prior systemic therapy for unresectable or metastatic melanoma with checkpoint inhibitors (CPI), either an anti-PD-1/PD-L1 as a single agent or in combination with anti-CTLA-4, investigational agents, chemotherapy or locally directed anti-neoplastic agents. Additionally, participants must have received targeted therapy with a RAFi as a single agent or in combination with a MEKi (+/- CPI allowed) as the last prior therapy.
• A maximum of two prior lines of systemic CPI-containing immunotherapy for unresectable or metastatic melanoma are allowed. Additional agents with CPI are permitted.
• A maximum of one line of targeted therapy is allowed, and it must be the most recent line of therapy.
• Participants must have documented progressive disease as per RECIST v1.1 while on/after treatment with targeted therapy. 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.
• = 2 weeks for small molecule therapeutics.
• = 4 weeks for any immunotherapy treatment including immune checkpoint inhibitors.
• = 4 weeks for chemotherapy agents, locally directed anti-neoplastic agents, or other investigational agents.
• = 6 weeks for cytotoxic agents with major delayed toxicities, such as nitrosourea and mitomycin c. 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

Related Conditions & MeSH terms

• Melanoma

Intervention

Drug:
• LXH254
LXH254 will be supplied as tablet for oral use.
• LTT462
LTT462 will be supplied as hard gelatin capsule for oral use.
• Trametinib
Trametinib will be supplied as film-coated tablet for oral use
• Ribociclib
Ribociclib will be supplied in tablets and hard gelatin capsules.

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Australia	Novartis Investigative Site	North Sydney	New South Wales
Australia	Novartis Investigative Site	Subiaco	Western Australia
Australia	Novartis Investigative Site	Wooloongabba	Queensland
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Wilrijk
France	Novartis Investigative Site	Lille
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Paris 10
France	Novartis Investigative Site	Pierre Benite
France	Novartis Investigative Site	Toulouse
France	Novartis Investigative Site	Villejuif
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Tuebingen
Israel	Novartis Investigative Site	Ramat Gan
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Napoli
Netherlands	Novartis Investigative Site	Maastricht
Norway	Novartis Investigative Site	Oslo
Switzerland	Novartis Investigative Site	Lausanne
Switzerland	Novartis Investigative Site	Zuerich
United Kingdom	Novartis Investigative Site	Manchester
United States	Dana Farber Cancer Institute Dept.of DFCI	Boston	Massachusetts
United States	Massachusetts General Hospital Massachusetts General Hospital	Boston	Massachusetts
United States	Florida Cancer Specialists Sarasota Office	Fort Myers	Florida
United States	Univ of TX MD Anderson Cancer Cntr .	Houston	Texas
United States	The Angeles Clinic and Research Institute .	Los Angeles	California
United States	Memorial Sloan Kettering Dept. of MSKCC	New York	New York
United States	NYU Laura and Isaac Perlmutter Cancer Center	New York	New York
United States	University of Pittsburgh Med Center	Pittsburgh	Pennsylvania
United States	Mayo Clinic Mayo Rochester	Rochester	Minnesota
United States	UCSF Medical Center .	San Francisco	California
United States	H Lee Moffitt Cancer Center and Research Institute Moffitt McKinley Outpatient Ct	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  France,  Germany,  Israel,  Italy,  Netherlands,  Norway,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate	Confirmed ORR using RECIST v1.1, per local assessment	35 months
Secondary	Duration of Reposnse (DOR)	Local and central assessment	4 years
Secondary	Progression Free Survival (PFS)		4 years
Secondary	Disease Control Rate (DCR)	Using RECIST v1.1, per local and central assessment	3 years
Secondary	Overall Survival (OS)		4 years
Secondary	Derived PK parameter (Cmax) for LXH254 & LTT462		Up to 5 months
Secondary	Derived PK parameter (Cmax) for LXH254 & trametinib		Up to 5 months
Secondary	Derived PK parameter (Cmax) for LXH254 & ribociclib		Up to 5 months
Secondary	Derived PK parameter (AUC) for LXH254 & LTT462		Up to 5 months
Secondary	Derived PK parameter (AUC) for LXH254 & trametinib		Up to 5 months
Secondary	Derived PK parameter (AUC) for LXH254 & ribociclib		Up to 5 months
Secondary	Incidence of adverse events (AEs) and serious adverse events (SAEs)	Number of participants with Adverse Events (AEs) and SAEs as a measure of safety and tolerability	35 months
Secondary	Dose Interruptions	Tolerability measured by the number of subjects who have interruptions of study treatment and reason for interruptions	35 months
Secondary	Dose reductions	Tolerability measured by the number of subjects who have reductions of study treatment and reason for reductions	35 months