A randomized, open-label, multi-arm, two-part, phase II study to assess the efficacy and safety of multiple LXH254 combinations in patients with previously treated unresectable or metastatic BRAFV600 or NRAS mutant melanoma

NOT ENROLLING
Protocol # :
20-472
Conditions
Melanoma
Phase
II
Disease Sites
Melanoma, Skin
Principal Investigator
Sullivan, Ryan, Joseph
Site Research Nurses
Finn, Kristen
Furtado, Mollie, E.
Gormley, Jill, Kathleen
Livengood, Amanda
Marujo, Rose
Mossali, Alexandra

Trial Description

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

Eligibility Requirements

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

20-472