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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03484923




Registration number
NCT03484923
Ethics application status
Date submitted
26/03/2018
Date registered
2/04/2018
Date last updated
24/04/2020

Titles & IDs
Public title
Study of Efficacy and Safety of Novel Spartalizumab Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma
Scientific 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
Secondary ID [1] 0 0
2018-000610-38
Secondary ID [2] 0 0
CPDR001J2201
Universal Trial Number (UTN)
Trial acronym
PLATforM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Spartalizumab
Treatment: Drugs - LAG525
Treatment: Drugs - Capmatinib
Treatment: Drugs - Canakinumab
Treatment: Drugs - Ribociclib

Experimental: LAG525 + Spartalizumab (PDR001) - Spartalizumab and LAG525 will be administered intravenously

Experimental: Capmatinib (INC280) and Spartalizumab (PDR001) - Spartalizumab will be administered intravenously. Capmatinib will be administered orally.

Experimental: Canakinumab and Spartalizumab (PDR001) - Spartalizumab will be administered intravenously. Canakinumab will be administered subcutaneously.

Experimental: Ribociclib (LEE011) and Spartalizumab (PDR001) - Spartalizumab will be administered intravenously. Ribociclib will be administered orally.


Treatment: Drugs: Spartalizumab
400 mg every 4 weeks intravenously (i.v)

Treatment: Drugs: LAG525
Taken intravenously (i.v)

Treatment: Drugs: Capmatinib
Taken orally

Treatment: Drugs: Canakinumab
Taken subcutaneusly (s.c)

Treatment: Drugs: Ribociclib
Taken orally

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (ORR) - 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 [1] 0 0
28 months
Secondary outcome [1] 0 0
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)
Timepoint [1] 0 0
Up to disease progression or death due to any cause, whichever occurs first (3 years)
Secondary outcome [2] 0 0
Overall Survival (OS) - OS defined as time from date of randomization to date of death due to any cause
Timepoint [2] 0 0
Up to death due to any cause (3 years)
Secondary outcome [3] 0 0
Progression Free Survival (PFS) - 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)
Timepoint [3] 0 0
Up to disease progression or death due to any cause, whichever occurs first (3 years)
Secondary outcome [4] 0 0
Disease Control Rate (DCR) - 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)
Timepoint [4] 0 0
Up to disease progression or death due to any cause, whichever occurs first (3 years)
Secondary outcome [5] 0 0
Prevalence of anti-drug antibodies (ADA) prevalence at baseline - Number of patients with presence of anti-drug antibodies (ADA)
Timepoint [5] 0 0
At Baseline
Secondary outcome [6] 0 0
Incidence of anti-drug antibodies (ADA) - Number of patients developing new anti-drug antibodies (ADA)
Timepoint [6] 0 0
Throughout study until 150 day after last drug administration
Secondary outcome [7] 0 0
Percentage of subjects with a favorable biomarker profile (pFBP) - 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 [7] 0 0
Baseline and after 3-4 weeks on treatment

Eligibility
Key inclusion 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 or conditions not expected
to recur in the absence of an external trigger 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
investigational agent, or 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). Prior
neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months before
the start of the study treatment (e.g targeted therapy, immunotherapy (e.g interferon,
checkpoint inhibitors or any other immunotherapy), chemotherapy and tumor vaccines).

- Medical history or current diagnosis of myocarditis

- Cardiac Troponin T (or Troponin I) level > 2 x ULN at screening
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Suspended
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Novartis Investigative Site - North Sydney
Recruitment hospital [2] 0 0
Novartis Investigative Site - Westmead
Recruitment postcode(s) [1] 0 0
2060 - North Sydney
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
Canada
State/province [7] 0 0
Quebec
Country [8] 0 0
France
State/province [8] 0 0
Marseille
Country [9] 0 0
France
State/province [9] 0 0
Paris Cedex 10
Country [10] 0 0
France
State/province [10] 0 0
Villejuif Cedex
Country [11] 0 0
Germany
State/province [11] 0 0
Dresden
Country [12] 0 0
Germany
State/province [12] 0 0
Essen
Country [13] 0 0
Germany
State/province [13] 0 0
Hamburg
Country [14] 0 0
Germany
State/province [14] 0 0
Kiel
Country [15] 0 0
Germany
State/province [15] 0 0
Muenchen
Country [16] 0 0
Italy
State/province [16] 0 0
BG
Country [17] 0 0
Italy
State/province [17] 0 0
MI
Country [18] 0 0
Italy
State/province [18] 0 0
Napoli
Country [19] 0 0
Netherlands
State/province [19] 0 0
Amsterdam
Country [20] 0 0
Netherlands
State/province [20] 0 0
Rotterdam
Country [21] 0 0
Spain
State/province [21] 0 0
Catalunya
Country [22] 0 0
Spain
State/province [22] 0 0
Madrid
Country [23] 0 0
Switzerland
State/province [23] 0 0
Zuerich
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Middlesex
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Newcastle Upon Tyne
Country [26] 0 0
United Kingdom
State/province [26] 0 0
London
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/show/NCT03484923
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03484923