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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03484923
Ethics application status
Date submitted
26/03/2018
Date registered
2/04/2018

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 - PDR001
Treatment: Drugs - LAG525
Treatment: Drugs - INC280
Treatment: Drugs - ACZ885
Treatment: Drugs - LEE011

Experimental: Arm 1: LAG525 + PDR001 (randomized section) - Participnats randomized to receive LAG525 at a dosage of 600 mg administered intravenously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks

Experimental: Arm 2: INC280+PDR001 (randomized section) - Participants randomized to receive INC280 orally at a dosage of 400 mg twice daily, in combination with PDR001 intravenously at a dosage of 400 mg every 4 weeks

Experimental: Arm 3: ACZ885 + PDR001 (randomized section) - Participants randomized to receive to receive ACZ885 at a dosage of 300 mg administered subcutaneously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks

Experimental: Arm 4: LEE011 + PDR001 (randomized section) - Participants randomized to receive LEE011 orally at a dosage of 600 mg once daily on Days 1-21 of a 28-day cycle, in combination with PDR001 intravenously at a dosage of 400 mg every 4 weeks

Experimental: Arm 1A: LAG525 + PDR001 (non-randomized section) - LAG-3 positive participants received LAG525 at a dosage of 600 mg administered intravenously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks


Treatment: Drugs: PDR001
400 mg of PDR001 administered every 4 weeks intravenously

Treatment: Drugs: LAG525
600 mg of LAG525 administered every 4 weeks intravenously

Treatment: Drugs: INC280
400 mg of INC280 administered twice daily orally

Treatment: Drugs: ACZ885
200 mg of ACZ885 administered every 4 weeks subcutaneosuly

Treatment: Drugs: LEE011
600 mg of LEE011 orally taken once daily on Days 1-21 of a 28-day cycle
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (ORR)
Timepoint [1] 0 0
Up to 49 months (randomized section) and 18 months (non-randomized section)
Secondary outcome [1] 0 0
Duration of Response (DOR)
Timepoint [1] 0 0
From first documented response to disease progression or death due to any cause, whichever occurs first, assessed up to 49 months (randomized part) and 18 months (non-randomized part)
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
From randomization (or start of treatment for non-randomized section) to death due to any cause, assessed up to 49 months (randomized section) and 24 months (non-randomized section)
Secondary outcome [3] 0 0
Progression Free Survival (PFS)
Timepoint [3] 0 0
From randomization (or start of treatment for non-randomized section) to disease progression or death due to any cause, whichever occurs first, assessed up to 49 months (randomized section) and 18 months (non-randomized section)
Secondary outcome [4] 0 0
Disease Control Rate (DCR)
Timepoint [4] 0 0
Up to 49 months (randomized section) and 18 months (non-randomized section)
Secondary outcome [5] 0 0
Percentage of Participants With PDR001 Anti-drug Antibodies (ADA) Positive Result at Baseline
Timepoint [5] 0 0
At Baseline
Secondary outcome [6] 0 0
Percentage of Participants With LAG525 Anti-drug Antibodies (ADA) Positive Result at Baseline
Timepoint [6] 0 0
At Baseline
Secondary outcome [7] 0 0
Percentage of Participants With ACZ885 Anti-drug Antibodies (ADA) Positive Result at Baseline
Timepoint [7] 0 0
At Baseline
Secondary outcome [8] 0 0
Percentage of Participants Who Were Treatment-induced ADA Positive and Treatment-boosted ADA Positive for PDR001
Timepoint [8] 0 0
Pre-infusion on Day 1 of Cycle 1, 2, 3, 4, 5, 6 and thereafter every 3 cycles until end of treatment (EOT), EOT, and 30 and 150 days post-EOT (assessed up to 49 months randomized section and 24 months non-randomized section). Cycle= 28 days
Secondary outcome [9] 0 0
Percentage of Participants Who Were Treatment-induced ADA Positive and Treatment-boosted ADA Positive for LAG525
Timepoint [9] 0 0
Pre-infusion on Day 1 of Cycle 1, 2, 3, 4, 5, 6 and thereafter every 3 cycles until end of treatment (EOT) and EOT (assessed up to 49 months in the randomized section and 18 months in the non-randomized section). Cycle= 28 days
Secondary outcome [10] 0 0
Percentage of Participants Who Were Treatment-induced ADA Positive and Treatment-boosted ADA Positive for ACZ885
Timepoint [10] 0 0
Pre-infusion on Day 1 of Cycle 1, 2, 3, 4, 5, 6 and thereafter every 3 cycles until end of treatment (EOT) and EOT (assessed up to 40 months). Cycle= 28 days
Secondary outcome [11] 0 0
Percentage of Participants With a Favorable Biomarker Profile (pFBP)
Timepoint [11] 0 0
Baseline and after 3-4 weeks of treatment

Eligibility
Key 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 had to 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 was allowed for advanced or metastatic melanoma.

A maximum of two prior lines of systemic therapies for unresectable or metastatic melanoma were allowed.

The last dose of prior therapy (anti-PD-1, anti-PD-L1, or anti-CTLA-4) had to have been received more than four weeks before randomization.

* Subjects with V600BRAF mutant disease had to 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 was allowed for advanced or metastatic melanoma.
* A maximum of three prior lines of systemic therapies for unresectable or metastatic melanoma were allowed.
* The last dose of prior therapy had to 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) had to 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 had to have occurred 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 the protocol. The same lesion had to be biopsied sequentially.
* Screening tumor biopsy had to 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 had to have received anti-PD-1 checkpoint inhibitor therapy (i.e., pembrolizumab or nivolumab) either as monotherapy or in combination with ipilimumab as the last systemic therapy prior to enrollment and had to have confirmed disease progression as per RECIST v1.1 (confirmed on a subsequent scan, which could be the scan performed during screening) while on or after this therapy prior to enrollment.
* Subjects with V600BRAF wild-type disease had to 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 had to 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 had to have been received more than four weeks prior to the first dose of study treatment.
* The last documented disease progression had to have occurred within 12 weeks prior to the first dose of study treatment.
* No additional systemic treatment was allowed for advanced or metastatic melanoma (this included, for example, tumor-infiltrating lymphocyte therapy).
* ECOG performance status 0-1.
* At least one measurable lesion per RECIST v1.1.
* Subjects had to have a baseline tumor sample that was positive for LAG-3 per central assessment.

Key exclusion criteria common to all combination arms:

* Subjects with uveal or mucosal melanoma.
* Presence of clinically active or unstable brain metastasis at the time of screening.
* Use of any live vaccines against infectious diseases within 3 months before randomization/enrollment.
* Active infection requiring systemic antibiotic therapy at the time of randomization/enrollment.
* Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization/enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses >10 mg daily prednisone equivalent, were 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.
* Malignant disease, other than that being treated 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 the 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.
Minimum age
18 Years
Maximum age
No limit
Sex
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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/09/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/12/2022
Sample size
Target
Accrual to date
Final
196
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
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario
Country [6] 0 0
Canada
State/province [6] 0 0
Quebec
Country [7] 0 0
France
State/province [7] 0 0
Marseille
Country [8] 0 0
France
State/province [8] 0 0
Paris 10
Country [9] 0 0
France
State/province [9] 0 0
Villejuif
Country [10] 0 0
Germany
State/province [10] 0 0
Dresden
Country [11] 0 0
Germany
State/province [11] 0 0
Essen
Country [12] 0 0
Germany
State/province [12] 0 0
Hamburg
Country [13] 0 0
Germany
State/province [13] 0 0
Kiel
Country [14] 0 0
Germany
State/province [14] 0 0
Muenchen
Country [15] 0 0
Italy
State/province [15] 0 0
BG
Country [16] 0 0
Italy
State/province [16] 0 0
MI
Country [17] 0 0
Italy
State/province [17] 0 0
Napoli
Country [18] 0 0
Netherlands
State/province [18] 0 0
Amsterdam
Country [19] 0 0
Netherlands
State/province [19] 0 0
Rotterdam
Country [20] 0 0
Spain
State/province [20] 0 0
Catalunya
Country [21] 0 0
Spain
State/province [21] 0 0
Madrid
Country [22] 0 0
Switzerland
State/province [22] 0 0
Zuerich
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Middlesex
Country [24] 0 0
United Kingdom
State/province [24] 0 0
London
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Manchester

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03484923