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
- Conditions
- BRAFV600 and NRAS mutant melanoma10040900
- Registration Number
- NL-OMON55115
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 18
Protocol language states : Male or female must be >= 12 years, in the
Netherlands only adults 18 years or older will be included.
- Histologically confirmed unresectable or metastatic cutaneous melanoma
- Previously treated for unresectable or metastatic melanoma:
- Participants with NRAS mutation:
- Pts must have received prior systemic therapy fo runresectable or metasttic
melanoma with checkpoint inhibitors (CPIs) either an anti-PD-1/PD-L1 as as
single agent or in combination with anti-CTLA-4, investigational agents,
chemotherapy or locally directed anti-neoplastic agents.
-Prior CPI therapy in the unresectable or metastatic setting is not required
for participants who have progressed on or within 6 months of adj. therapy with
a CPI
-Prior therapy with T-VEC 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.
- Particitpants must have documented confirmed progressive dissease as per
iRecist v1.1 while on/after therapy with CPI. Confirmation is not required for
pts who remained on treatment > 6 months.
- Participants with BRAFV600 mutant disease:
- Pts must have received prior systemic therapy for unresectable or metatstic
melanoma with a checkpoint inhibitor (CPI) either an anti-PD-1/PD-L1 as single
agent or in combination with anti-CTLA-4, investigational agents, chemotherapy
or locally directed anti-neoplastic agents. additionall pts must have receied
targeted therapy with a RAFi as a single agent or in combination with a MEKi
(+/- CPI allowed) as the last prior therapy.
- Prior CPI therapy in the unresectable or metastatic setting is not required
for participants who have progresssed on or within 6 months of adjuvant CPI.
- Prior therapy with T-VEC is allowed and will not be counted as a prior line
of systemic therapy.
- A maximum of two lines of CPI-containing therapy systemic immunotherapy for
unresectable or metatstatic 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.
- Pts must have documented progressive disease as per recist v1.1 while
on/after treatment with targeted therapy.
Other protocol-defined inclusion criteria may apply.
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 neitrosourea 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
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Objective response rate as determined by local assessment through (i)RECIST<br /><br>v1.1</p><br>
- Secondary Outcome Measures
Name Time Method <p>Safety, tolerability, efficacy through duration of reponse, progression free<br /><br>survival, disease control rate and overall survival. </p><br>