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

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ClinicalTrials.gov Identifier: NCT03484923
Recruitment Status : Recruiting
First Posted : April 2, 2018
Last Update Posted : June 24, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

Condition or disease Intervention/treatment Phase
Melanoma Drug: Spartalizumab Drug: LAG525 Drug: Capmatinib Drug: Canakinumab Drug: Ribociclib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 230 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 10, 2018
Estimated Primary Completion Date : August 7, 2020
Estimated Study Completion Date : June 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: LAG525 + Spartalizumab (PDR001)
Spartalizumab and LAG525 will be administered intravenously
Drug: Spartalizumab
400 mg every 4 weeks intravenously (i.v)
Other Name: PDR001

Drug: LAG525
Taken intravenously (i.v)

Experimental: Capmatinib (INC280) and Spartalizumab (PDR001)
Spartalizumab will be administered intravenously. Capmatinib will be administered orally.
Drug: Spartalizumab
400 mg every 4 weeks intravenously (i.v)
Other Name: PDR001

Drug: Capmatinib
Taken orally
Other Name: INC280

Experimental: Canakinumab and Spartalizumab (PDR001)
Spartalizumab will be administered intravenously. Canakinumab will be administered subcutaneously.
Drug: Spartalizumab
400 mg every 4 weeks intravenously (i.v)
Other Name: PDR001

Drug: Canakinumab
Taken subcutaneusly (s.c)

Experimental: Ribociclib (LEE011) and Spartalizumab (PDR001)
Spartalizumab will be administered intravenously. Ribociclib will be administered orally.
Drug: Spartalizumab
400 mg every 4 weeks intravenously (i.v)
Other Name: PDR001

Drug: Ribociclib
Taken orally
Other Name: LEE011




Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 28 months ]
    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 :
  1. Duration of Response [ Time Frame: Up to disease progression or death due to any cause, whichever occurs first (3 years) ]
    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)

  2. Overall Survival (OS) [ Time Frame: Up to death due to any cause (3 years) ]
    OS defined as time from date of randomization to date of death due to any cause

  3. Progression Free Survival (PFS) [ Time Frame: Up to disease progression or death due to any cause, whichever occurs first (3 years) ]
    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)

  4. Disease Control Rate (DCR) [ Time Frame: Up to disease progression or death due to any cause, whichever occurs first (3 years) ]
    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)

  5. Prevalence of anti-drug antibodies (ADA) prevalence at baseline [ Time Frame: At Baseline ]
    Number of patients with presence of anti-drug antibodies (ADA)

  6. Incidence of anti-drug antibodies (ADA) [ Time Frame: Throughout study until 150 day after last drug administration ]
    Number of patients developing new anti-drug antibodies (ADA)

  7. Percentage of subjects with a favorable biomarker profile (pFBP) [ Time Frame: Baseline and after 3-4 weeks on treatment ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03484923


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

  Show 32 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03484923     History of Changes
Other Study ID Numbers: CPDR001J2201
2018-000610-38 ( EudraCT Number )
First Posted: April 2, 2018    Key Record Dates
Last Update Posted: June 24, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
PDR001
Unresectable
melanoma
metastatic melanoma
advanced melanoma
spartalizumab
LAG525
capmatinib
INC280
canakinumab
ACZ885
ribociclib
LEE011
immunotherapy
platform study

Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs