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Study of Efficacy and Safety of Novel Spartalizumab Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma

NCT03484923

Description:

The primary purpose of this study is to evaluate the efficacy of novel spartalizumab (PDR001) combinations in previously treated unresectable or metastatic melanoma

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Efficacy and Safety of Novel Spartalizumab Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma
  • Official Title: A Randomized, Open-label, Phase II Open Platform Study Evaluating the Efficacy and Safety of Novel Spartalizumab (PDR001) Combinations in Previously Treated Unresectable or Metastatic Melanoma

Clinical Trial IDs

  • ORG STUDY ID: CPDR001J2201
  • SECONDARY ID: 2018-000610-38
  • NCT ID: NCT03484923

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
SpartalizumabPDR001LAG525 + Spartalizumab (PDR001)
LAG525LAG525 + Spartalizumab (PDR001)
CapmatinibINC280Capmatinib (INC280) and Spartalizumab (PDR001)
CanakinumabCanakinumab and Spartalizumab (PDR001)
RibociclibLEE011Ribociclib (LEE011) and Spartalizumab (PDR001)

Purpose

The primary purpose of this study is to evaluate the efficacy of novel spartalizumab (PDR001) combinations in previously treated unresectable or metastatic melanoma

Trial Arms

NameTypeDescriptionInterventions
LAG525 + Spartalizumab (PDR001)ExperimentalSpartalizumab and LAG525 will be administered intravenously
  • Spartalizumab
  • LAG525
Capmatinib (INC280) and Spartalizumab (PDR001)ExperimentalSpartalizumab will be administered intravenously. Capmatinib will be administered orally.
  • Spartalizumab
  • Capmatinib
Canakinumab and Spartalizumab (PDR001)ExperimentalSpartalizumab will be administered intravenously. Canakinumab will be administered subcutaneously.
  • Spartalizumab
  • Canakinumab
Ribociclib (LEE011) and Spartalizumab (PDR001)ExperimentalSpartalizumab will be administered intravenously. Ribociclib will be administered orally.
  • Spartalizumab
  • Ribociclib

Eligibility Criteria

        Key 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 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 systemic therapy 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 exclusion criteria common to all combination arms:

          -  Subjects with uveal or mucosal melanoma

          -  Presence of clinically active or unstable brain metastasis at time of screening. Note:
             Subjects with previously 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 randomization.

          -  Use of any live vaccines against infectious diseases within 3 months before
             randomization.

          -  Active infection requiring systemic antibiotic therapy at time of randomization.

          -  Systemic chronic steroid therapy (˃ 10mg/day prednisone or equivalent) or any other
             immunosuppressive therapy administered within 7 days prior to randomization. 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 autoimmune-related 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

          -  Prior systemic therapy for unresectable or metastatic melanoma with any other agent
             except anti-PD-1/PD-L1 and anti-CTLA-4 (and V600BRAF and MEK inhibitors if subject has
             V600BRAF mutant disease).

          -  Medical history or current diagnosis of myocarditis

          -  Cardiac Troponin T (or Troponin I) level > 2 x ULN at screening
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:28 months
Safety Issue:
Description: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)

Secondary Outcome Measures

Measure:Duration of Response
Time Frame:Up to disease progression or death due to any cause, whichever occurs first (3 years)
Safety Issue:
Description: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)
Measure:Overall Survival (OS)
Time Frame:Up to death due to any cause (3 years)
Safety Issue:
Description:OS defined as time from date of randomization to date of death due to any cause
Measure:Progression Free Survival (PFS)
Time Frame:Up to disease progression or death due to any cause, whichever occurs first (3 years)
Safety Issue:
Description: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)
Measure:Disease Control Rate (DCR)
Time Frame:Up to disease progression or death due to any cause, whichever occurs first (3 years)
Safety Issue:
Description: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)
Measure:Prevalence of anti-drug antibodies (ADA) prevalence at baseline
Time Frame:At Baseline
Safety Issue:
Description:Number of patients with presence of anti-drug antibodies (ADA)
Measure:Incidence of anti-drug antibodies (ADA)
Time Frame:Throughout study until 150 day after last drug administration
Safety Issue:
Description:Number of patients developing new anti-drug antibodies (ADA)
Measure:Percentage of subjects with a favorable biomarker profile (pFBP)
Time Frame:Baseline and after 3-4 weeks on treatment
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Unresectable
  • melanoma
  • metastatic melanoma
  • advanced melanoma
  • spartalizumab
  • PDR001
  • LAG525
  • capmatinib
  • INC280
  • canakinumab
  • ACZ885
  • ribociclib
  • LEE011
  • immunotherapy
  • platform study

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