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: Key inclusion criteria for Arm 1,2,3,4: • Histologically confirmed unresectable or metastatic stage IIIB/C/D or IV melanoma using AJCC edition 8 • Previously treated for unresectable or metastatic melanoma: • Subjects with V600BRAF wild-type disease must have received prior systemic therapy for unresectable or metastatic melanoma with anti-PD-1/PD-L1. Additionally, subjects may have received anti-CTLA-4 as a single agent or in combination with anti- PD-1/PD-L1, irrespective of the sequence. No additional systemic treatment is allowed for advanced or metastatic melanoma. A maximum of two prior lines of systemic therapies 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. • Subjects with V600BRAF mutant disease must have received prior systemictherapy for unresectable or metastatic melanoma with anti-PD-1/PD-L1, and V600BRAF inhibitor. Additionally, subjects may have received anti-CTLA-4 as a single agent or in combination with anti-PD-1/PD-L1, or MEK inhibitor (in combination with V600BRAF inhibitor or as a single agent), irrespective of the sequence. No additional systemic treatment is allowed for advanced or metastatic melanoma . A maximum of three prior lines of systemic therapies for unresectable or metastatic melanoma are allowed. The last dose of prior therapy must have been received more than 4 weeks (for anti- PD-1, anti-PD-L1 or anti-CTLA-4) or more than 2 weeks (for V600BRAF or MEK inhibitor) prior to randomization. • All subjects (with V600BRAF wild-type disease and with V600BRAF mutant disease) must have documented disease progression as per RECIST v1.1 while on/after the last therapy received prior to study entry and while on/after treatment with anti-PD1/PD-L1. The last progression must have occured within 12 weeks prior to randomization in the study. • 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 Key inclusion criteria for Arm 1A: • Histologically confirmed unresectable or metastatic stage IIIB/C/D or IV melanoma according to AJCC Edition 8 • Previously treated for unresectable or metastatic melanoma: - All subjects must have received anti-PD-1 checkpoint inhibitor therapy (ie. pembrolizumab or nivolumab) either as monotherapy or in combination with ipilimumab as the last systemic therapy prior to enrollment and must have confirmed disease progression as per RECIST v1.1 (confirmed on a subsequent scan, which can be the scan performed during screening) while on or after this therapy prior to enrollment. - Subjects with V600BRAF wild-type disease must have received no more than 2 prior systemic therapies including prior anti-PD-1/PD-L1 (as monotherapy or in combination with ipilimumab) - Subjects with V600BRAF mutant disease must have received no more than 3 prior systemic therapies including anti-PD-1/PD-L1 (as monotherapy or in combination with ipilimumab), and V600BRAF inhibitor (as monotherapy or in combination with a MEK inhibitor) - The last dose of anti-PD-1 based therapy must have been received more than four weeks
Exclusion criteria
Exclusion criteria: • Subjects with uveal or mucosal melanoma • Presence of clinically active or unstable brain metastasis at time of screening. • Use of any live vaccines against infectious diseases within 3 months before randomization/enrolment. • Active infection requiring systemic antibiotic therapy at time of randomization/enrolment. • Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive médications within 14 days of randomization/enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses >10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. • Active, known or suspected autoimmune disease or a documented history of autoimmune disease. • Prior allogenic bone marrow or solid organ transplant • History of known hypersensitivity to any of the investigational drugs used in this study • Prior systemic therapy for unresectable or metastatic melanoma with any investigational agent, or with any other agent except anti-PD-1/PDL1 and anti-CTLA-4 (and V600BRAF and MEK inhibitors if subject has V600BRAF mutant disease). Prior neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months before the start of the study treatment • Medical history or current diagnosis of myocarditis • Cardiac Troponin T (or Troponin I) level > 2 x ULN at screening 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: 38 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 (or date of first dose of study treatment in arm 1A) to date of death due to any cause - Progression Free Survival (PFS) defined as the interval of time between the date of randomization (or date of first dose of study treatment in arm 1A) 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 ContactClinical Trial Information Desk
Novartis Pharma AG
Outcome results
None listed