Study of efficacy and safety of LXH254 combinations in patients with previously treated unresectable or metastatic melanoma

Phase 1

• Conditions: previously treated unresectable or metastatic BRAFV600 or NRAS mutant melanoma; MedDRA version: 21.1Level: PTClassification code 10027480Term: Metastatic malignant melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10027150Term: Melanoma malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-000873-26-PL
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-11-25
• Last Update Posted: 19 April 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 320

Inclusion Criteria

- Male or female must be = 12 years
- 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.

Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 55

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).
-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.
-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 inclusion/exclusion criteria may apply

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the anti-tumor efficacy of LXH254 in combination with novel agents including LTT462, trametinib, ribociclib in participants with previously treated unresectable or metastatic, BRAFV600 or NRAS mutant melanoma as measured by objective response rate.;Secondary Objective: - To characterize the safety and tolerability of each combination arm<br>- To further evaluate the efficacy of each combination arm<br>- To evaluate the OS of each combination arm<br>- To characterize the pharmacokinetics of each combination regimen;Primary end point(s): Confirmed objective response rate (ORR) using RECIST v1.1, per local assessment;Timepoint(s) of evaluation of this end point: Patient has at least 8 months or has progressed, died, discontinued study or started new anti-neoplastic therapy earlier.