Study of Efficacy and Safety of Novel Spartalizumab Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma
PLATforM
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
2 other identifiers
interventional
196
10 countries
30
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 Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Sep 2018
Typical duration for phase_2
30 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 26, 2018
CompletedFirst Posted
Study publicly available on registry
April 2, 2018
CompletedStudy Start
First participant enrolled
September 10, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 30, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
December 30, 2022
CompletedResults Posted
Study results publicly available
January 18, 2024
CompletedJune 18, 2024
June 1, 2024
4.3 years
March 26, 2018
December 20, 2023
June 14, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Response Rate (ORR)
ORR defined as the percentage of patients with a best overall response of either confirmed complete response (CR) or partial response (PR) as per local review by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and assessed by computed tomography (CT)/ magnetic resonance imaging (MRI). CR:Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Up to 49 months (randomized section) and 18 months (non-randomized section)
Secondary Outcomes (11)
Duration of Response (DOR)
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)
Overall Survival (OS)
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)
Progression Free Survival (PFS)
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)
Disease Control Rate (DCR)
Up to 49 months (randomized section) and 18 months (non-randomized section)
Percentage of Participants With PDR001 Anti-drug Antibodies (ADA) Positive Result at Baseline
At Baseline
- +6 more secondary outcomes
Study Arms (5)
Arm 1: LAG525 + PDR001 (randomized section)
EXPERIMENTALParticipnats 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
Arm 2: INC280+PDR001 (randomized section)
EXPERIMENTALParticipants 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
Arm 3: ACZ885 + PDR001 (randomized section)
EXPERIMENTALParticipants 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
Arm 4: LEE011 + PDR001 (randomized section)
EXPERIMENTALParticipants 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
Arm 1A: LAG525 + PDR001 (non-randomized section)
EXPERIMENTALLAG-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
Interventions
400 mg of PDR001 administered every 4 weeks intravenously
600 mg of LAG525 administered every 4 weeks intravenously
400 mg of INC280 administered twice daily orally
200 mg of ACZ885 administered every 4 weeks subcutaneosuly
600 mg of LEE011 orally taken once daily on Days 1-21 of a 28-day cycle
Eligibility Criteria
You may qualify if:
- 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.
- Histologically confirmed unresectable or metastatic stage IIIB/C/D or IV melanoma according to AJCC Edition 8.
- Previously treated for unresectable or metastatic melanoma:
- +9 more criteria
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (30)
The Angeles Clinic and Research Institute
Los Angeles, California, 90025, United States
University of California Los Angeles
Los Angeles, California, 90095, United States
UCSF Medical Center .
San Francisco, California, 94143, United States
Massachusetts General Hospital Massachusetts Gen. Hospital CC
Boston, Massachusetts, 02114, United States
NYU Laura and Isaac Perlmutter Cancer Center Perlmutter Cancer Center
New York, New York, 10016, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232, United States
Novartis Investigative Site
North Sydney, New South Wales, 2060, Australia
Novartis Investigative Site
Westmead, New South Wales, 2145, Australia
Novartis Investigative Site
Toronto, Ontario, M5G 2M9, Canada
Novartis Investigative Site
Montreal, Quebec, H3T 1E2, Canada
Novartis Investigative Site
Marseille, 13009, France
Novartis Investigative Site
Paris, 75475, France
Novartis Investigative Site
Villejuif, 94800, France
Novartis Investigative Site
Dresden, 01307, Germany
Novartis Investigative Site
Essen, 45147, Germany
Novartis Investigative Site
Hamburg, 20246, Germany
Novartis Investigative Site
Kiel, 24105, Germany
Novartis Investigative Site
München, 81377, Germany
Novartis Investigative Site
Bergamo, BG, 24127, Italy
Novartis Investigative Site
Milan, MI, 20133, Italy
Novartis Investigative Site
Napoli, 80131, Italy
Novartis Investigative Site
Amsterdam, 1066 CX, Netherlands
Novartis Investigative Site
Rotterdam, 3015 GD, Netherlands
Novartis Investigative Site
Barcelona, Catalonia, 08036, Spain
Novartis Investigative Site
L'Hospitalet de Llobregat, Catalonia, 08907, Spain
Novartis Investigative Site
Madrid, 28009, Spain
Novartis Investigative Site
Zurich, 8091, Switzerland
Novartis Investigative Site
Northwood, Middlesex, HA6 2RN, United Kingdom
Novartis Investigative Site
London, SW3 6JJ, United Kingdom
Novartis Investigative Site
Manchester, M20 4BX, United Kingdom
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Masking Details
- After approval of protocol amendment 5 (26Jun2020), a non-randomized single arm was added
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 26, 2018
First Posted
April 2, 2018
Study Start
September 10, 2018
Primary Completion
December 30, 2022
Study Completion
December 30, 2022
Last Updated
June 18, 2024
Results First Posted
January 18, 2024
Record last verified: 2024-06
Data Sharing
- IPD Sharing
- Will share
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.