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-DE
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-07-29
• Last Update Posted: 18 June 2024

Recruitment & Eligibility

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

Inclusion Criteria

- Male or female must be = 18 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 checkpoint inhibitor as a single agent or in combination with anti-CTLA-4, investigational agents, chemotherapy or locally directed antineoplastic
agents.
Prior checkpoint inhibitor therapy in the unresectable or metastatic setting is not required for participants who have progressed on or within 6 months of adjuvant therapy with a checkpoint inhibitor
- Prior therapy with T-VEC (talimogene laherparepvec) is allowed and will not be counted as a prior line of systematic therapy
- A maximum of two prior lines of systemic CPI-containing immunotherapy for unresectable or metastatic melanoma are allowed Additional agents administered with a 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 >6 months.- Participants with BRAFV600 mutant disease:
- Participants must have received prior systemic therapy for unresectable or metastatic melanoma with a checkpoint inhibitor (CPI), 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.
Prior checkpoint inhibitor therapy in the unresectable or metastatic setting is not required for participants who have progressed on or within 6 months of adjuvant checkpoint inhibitors.
- Prior therapy with T-VEC (talimogene laherparepvec) is allowed and will not be counted as a prior line of systematic therapy
- A maximum of two prior lines of CPI-containing systemic 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
- If a participant discontinued targeted therapy for reasons other than disease progression, a switch to another targeted therapy regimen is allowed
- 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 265
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