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

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

ClinicalTrials.gov Identifier: NCT03484923

Novartis Reference Number: CPDR001J2201

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

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

Condition 
Melanoma
Phase 
Phase 2
Overall status 
Recruiting
Enrollment count 
195 participants
Start date 
Sep 10, 2018
Completion date 
Apr 15, 2022
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
Spartalizumab
400 mg every 4 weeks intravenously (i.v)
Drug
LAG525
Taken intravenously (i.v)
Drug
Capmatinib
Taken orally
Drug
Canakinumab
Taken subcutaneusly (s.c)
Drug
Ribociclib
Taken orally

Eligibility 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 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 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 must have received anti-PD-1 checkpoint inhibitor therapy (ie. pembrolizumab or nivolumab) either as monotherapy or in combination with ipilimumab as the last systemic therapy prior to enrollment and must have confirmed disease progression as per RECIST v1.1 (confirmed on a subsequent scan, which can be the scan performed during screening) while on or after this therapy prior to enrollment.
Subjects with V600BRAF wild-type disease must 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 must 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 must have been received more than four weeks prior to first dose of study treatment.
The last documented disease progression must have occurred within 12 weeks prior to first dose of study treatment
No additional systemic treatment is allowed for advanced or metastatic melanoma (this includes for example tumor infiltrating lymphocyte therapy)
ECOG performance status 0-1
At least one measurable lesion per RECIST v1.1
Subjects must have baseline tumor sample that is 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 time of screening.
Use of any live vaccines against infectious diseases within 3 months before randomization/enrolment.
Active infection requiring systemic antibiotic therapy at time of randomization/enrolment.
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, are 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
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
Medical history or current diagnosis of myocarditis
Cardiac Troponin T (or Troponin I) level > 2 x ULN at screening

Study Locations

United States
The Angeles Clinic and Research Institute
Recruiting
Los Angeles, 90025
California
United States
University of California Los Angeles
Recruiting
Los Angeles, 90095
California
United States
UCSF Medical Center
Recruiting
San Francisco, 94143
California
United States
Georgetown University/Lombardi Cancer Center CERL080AUS67
Recruiting
Washington, 20007
District of Columbia
United States
Massachusetts General Hospital Massachusetts Gen. Hospital CC
Recruiting
Boston, 02114
Massachusetts
United States
Dana Farber Cancer Institute
Recruiting
Boston, 02115
Massachusetts
United States
NYU Laura and Isaac Perlmutter Cancer Center Perlmutter Cancer Center
Recruiting
New York, 10016
New York
United States
University of Pittsburgh Medical Center
Recruiting
Pittsburgh, 15232
Pennsylvania
United States
Australia
Novartis Investigative Site
Recruiting
North Sydney, 2060
New South Wales
Australia
Novartis Investigative Site
Recruiting
Westmead, 2145
New South Wales
Australia
Canada
Novartis Investigative Site
Recruiting
Toronto, M5G 2M9
Ontario
Canada
Novartis Investigative Site
Recruiting
Montreal, H3T 1E2
Quebec
Canada
France
Novartis Investigative Site
Recruiting
Marseille, 13009
-
France
Novartis Investigative Site
Recruiting
Paris Cedex 10, 75475
-
France
Novartis Investigative Site
Recruiting
Villejuif Cedex, 94800
-
France
Germany
Novartis Investigative Site
Recruiting
Dresden, 01307
-
Germany
Novartis Investigative Site
Recruiting
Essen, 45147
-
Germany
Novartis Investigative Site
Recruiting
Hamburg, 20246
-
Germany
Novartis Investigative Site
Recruiting
Kiel, 24105
-
Germany
Novartis Investigative Site
Recruiting
Muenchen, 81377
-
Germany
Italy
Novartis Investigative Site
Active, not recruiting
Bergamo, 24127
BG
Italy
Novartis Investigative Site
Active, not recruiting
Milano, 20133
MI
Italy
Novartis Investigative Site
Recruiting
Napoli, 80131
-
Italy
Netherlands
Novartis Investigative Site
Recruiting
Amsterdam, 1066 CX
-
Netherlands
Novartis Investigative Site
Recruiting
Rotterdam, 3015 GD
-
Netherlands
Spain
Novartis Investigative Site
Recruiting
Barcelona, 08036
Catalunya
Spain
Novartis Investigative Site
Recruiting
Hospitalet de LLobregat, 08907
Catalunya
Spain
Novartis Investigative Site
Recruiting
Madrid, 28009
-
Spain
Switzerland
Novartis Investigative Site
Recruiting
Zuerich, 8091
-
Switzerland
United Kingdom
Novartis Investigative Site
Recruiting
Northwood, HA6 2RN
Middlesex
United Kingdom
Novartis Investigative Site
Recruiting
High Heaton, NE7 7DN
Newcastle Upon Tyne
United Kingdom
Novartis Investigative Site
Recruiting
London, SW3 6JJ
-
United Kingdom
Novartis Investigative Site
Recruiting
Manchester, M20 9BX
-
United Kingdom

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
1-888-669-6682
Name: 
Novartis Pharmaceuticals
Phone: 
+41613241111
Email: 

Have a question?

Call 1-999-669-6682 or email [email protected]