Unresectable or metastatic melanoma MedDRA version: 20.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 100000004864
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically confirmed unresectable or metastatic stage IIIB/C/D or IV melanoma using AJCC edition 8 • Previously treated for unresectable or metastatic melanoma. Subjects must have at least received the following treatments: -V600BRAF wild-type patients: must have received anti-PD-1/PD-L1 single-agent, or in combination with anti-CTLA-4 therapy -V600BRAF mutant patients: must have received prior anti-PD-1/PD-L1 single-agent, or in combination with anti-CTLA-4 therapy. In addition, subjects must have received prior V600BRAF inhibitor therapy, either single-agent or in combination with a MEK inhibitor • ECOG performance status 0-2 • At least one measurable lesion per RECIST v1.1 • At least one lesion, suitable for sequential mandatory tumor biopsies (screening and on-treatment) in accordance with the biopsy guidelines specified in protocol. The same lesion must be biopsied sequentially. • Screening tumor biopsy must fulfill the tissue quality criteria outlined in the protocol, as assessed by a local pathologist Other 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 120 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: • Subjects with uveal or mucosal melanoma • Presence of clinically active or unstable brain metastasis. Note: Subjects with unstable brain lesions who have been definitively treated with stereotactic radiation therapy, surgery or gamma knife therapy are eligible. - Subjects with brain lesions who are untreated (i.e. newly discovered brain lesions during screening) or received whole brain radiation must have documented stable disease as assessed by two consecutive assessments = 4 weeks apart and have not required steroids for at least = 4 weeks prior to enrollment. • Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment. • Active infection requiring systemic antibiotic therapy. • Systemic chronic steroid therapy (> 10mg/day prednisone or equivalent) or any other immunosuppressive therapy 7 days prior to planned date of first dose of study treatment. Note: Local steroids such as topical, inhaled, nasal and ophthalmic steroids are allowed. • Active, known or suspected autoimmune disease or a documented history of autoimmune disease. Note: Subjects with vitiligo, controlled type I diabetes mellitus on stable insulin dose, residual autoimmunerelated hypothyroidism only requiring hormone replacement or psoriasis not requiring systemic treatment are permitted. • Prior allogenic bone marrow or solid organ transplant • History of known hypersensitivity to any of the investigational drugs used in this study Other exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of each combination arm, as measured by objective response rate (ORR) ;Secondary Objective: Key secondary: To evaluate the efficacy of each combination arm in terms of duration of response (DoR) Other secondary objectives : - To evaluate the efficacy of each combination arm in terms of progression-free survival (PFS) and disease control rate (DCR) -To evaluate the overall survival (OS) of each combination arm -To characterize the safety and tolerability of each combination arm -To characterize the prevalence and incidence of immunogenicity of spartalizumab, LAG525 and canakinumab in each combination arm -To evaluate changes in levels and phenotype of T cell populations in the tumor and tumor microenvironment after treatment with combination therapies;Primary end point(s): Overall Response Rate (ORR) defined as the proportion of patients with a best overall response of either confirmed complete response or confirmed partial response (as per local review and according to RECIST v1.1);Timepoint(s) of evaluation of this end point: 28 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Duration of Response (DOR) defined as the time from date of first documented complete response or partial response to date of first documented disease progression or death due to any cause (as per local review and according to RECIST v1.1) - Overall Survival (OS) defined as time from date of randomization to date of death due to any cause - Progression Free Survival (PFS) defined as the interval of time between the date of randomization to the date of event defined as the first documented disease progression or death due to any cause (as per local review and according to RECIST v1.1) - Disease Control Rate (DCR) defined as the proportion of patients with best overall response of complete response, partial response, or stable disease (as per local review and according to RECIST v1.1) - Prevalence of anti-drug antibodies (ADA) at baseline: number of patients with presence of ADA - Incidence of anti-drug antibodies (ADA): number of patients developing new ADA - Percentage of subjects with a favorable biomarker profile (pFBP) defined by changes in number of cells expressing the CD8+ T cell marker and/or T cell activation marker(s), T cell clonality and/or gene expression tumor biosy samples.;Timepoint(s) of evaluation of this end point: - DOR: Up to disease progression or death due to any cause, whichever occurs first (3 years) - OS: Up to death due to any cause (3 years) - PFS: Up to disease progression or death due to any cause, whichever occurs first (3 years) - DCR: Up to disease progression or death due to any cause, whichever occurs first (3 years) - Prevalence of ADA prevalence at baseline: at baseline - Incidence of ADA: Throughout study until 150 day after last drug administration - pFBP: Baseline and after 3-4 weeks on treatment | — |
Countries
Australia, Canada, France, Germany, Italy, Netherlands, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactInformation&Communication Médicales
Novartis Pharma S.A.S
Outcome results
None listed