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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03484923

Collaborator

(none)

196

Enrollment

Locations

Arms

56.2

Anticipated Duration (Months)

6.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

196 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

4 arms are included in the randomized part of the study. One arm is included in the non-randomized part of the study.4 arms are included in the randomized part of the study. One arm is included in the non-randomized part of the study.

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 :

Sep 10, 2018

Anticipated Primary Completion Date :

Dec 28, 2022

Anticipated Study Completion Date :

May 17, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: LAG525 + Spartalizumab in unselected patients Spartalizumab and LAG525 will be administered intravenously	Drug: Spartalizumab 400 mg every 4 weeks intravenously (i.v) Other Names: PDR001 Drug: LAG525 Taken intravenously (i.v)
Experimental: Arm 2: Capmatinib+Spartalizumab in unselected patients Spartalizumab will be administered intravenously. Capmatinib will be administered orally.	Drug: Spartalizumab 400 mg every 4 weeks intravenously (i.v) Other Names: PDR001 Drug: Capmatinib Taken orally Other Names: INC280
Experimental: Arm 3: Canakinumab+Spartalizumab in unselected patients Spartalizumab will be administered intravenously. Canakinumab will be administered subcutaneously.	Drug: Spartalizumab 400 mg every 4 weeks intravenously (i.v) Other Names: PDR001 Drug: Canakinumab Taken subcutaneusly (s.c) Other Names: ACZ885
Experimental: Arm 4: Ribociclib+Spartalizumab in unselected patients Spartalizumab will be administered intravenously. Ribociclib will be administered orally.	Drug: Spartalizumab 400 mg every 4 weeks intravenously (i.v) Other Names: PDR001 Drug: Ribociclib Taken orally Other Names: LEE011
Experimental: Arm 1A: LAG525 + Spartalizumab in LAG-3 positive patients Spartalizumab and LAG525 will be administered intravenously	Drug: Spartalizumab 400 mg every 4 weeks intravenously (i.v) Other Names: PDR001 Drug: LAG525 Taken intravenously (i.v)

Outcome Measures

Primary Outcome Measures

Overall Response Rate (ORR) [38 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

Duration of Response [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)
Overall Survival (OS) [Up to death due to any cause (3 years)]
OS defined as time from date of randomization (or date of first dose of study treatment in arm 1A) to date of death due to any cause
Progression Free Survival (PFS) [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 (or date of first dose of study treatment in arm 1A) 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)
Disease Control Rate (DCR) [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)
Prevalence of anti-drug antibodies (ADA) prevalence at baseline [At Baseline]
Number of patients with presence of anti-drug antibodies (ADA)
Incidence of anti-drug antibodies (ADA) [Throughout study until 150 day after last drug administration]
Number of patients developing new anti-drug antibodies (ADA)
Percentage of subjects with a favorable biomarker profile (pFBP) [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Angeles Clinic and Research Institute	Los Angeles	California	United States	90025
2	University of California Los Angeles	Los Angeles	California	United States	90095
3	UCSF Medical Center	San Francisco	California	United States	94143
4	Georgetown University/Lombardi Cancer Center CERL080AUS67	Washington	District of Columbia	United States	20007
5	Massachusetts General Hospital Massachusetts Gen. Hospital CC	Boston	Massachusetts	United States	02114
6	NYU Laura and Isaac Perlmutter Cancer Center Perlmutter Cancer Center	New York	New York	United States	10016
7	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15232
8	Novartis Investigative Site	North Sydney	New South Wales	Australia	2060
9	Novartis Investigative Site	Westmead	New South Wales	Australia	2145
10	Novartis Investigative Site	Toronto	Ontario	Canada	M5G 2M9
11	Novartis Investigative Site	Montreal	Quebec	Canada	H3T 1E2
12	Novartis Investigative Site	Marseille		France	13009
13	Novartis Investigative Site	Paris Cedex 10		France	75475
14	Novartis Investigative Site	Villejuif Cedex		France	94800
15	Novartis Investigative Site	Dresden		Germany	01307
16	Novartis Investigative Site	Essen		Germany	45147
17	Novartis Investigative Site	Hamburg		Germany	20246
18	Novartis Investigative Site	Kiel		Germany	24105
19	Novartis Investigative Site	Muenchen		Germany	81377
20	Novartis Investigative Site	Bergamo	BG	Italy	24127
21	Novartis Investigative Site	Milano	MI	Italy	20133
22	Novartis Investigative Site	Napoli		Italy	80131
23	Novartis Investigative Site	Amsterdam		Netherlands	1066 CX
24	Novartis Investigative Site	Rotterdam		Netherlands	3015 GD
25	Novartis Investigative Site	Barcelona	Catalunya	Spain	08036
26	Novartis Investigative Site	Hospitalet de LLobregat	Catalunya	Spain	08907
27	Novartis Investigative Site	Madrid		Spain	28009
28	Novartis Investigative Site	Zuerich		Switzerland	8091
29	Novartis Investigative Site	Northwood	Middlesex	United Kingdom	HA6 2RN
30	Novartis Investigative Site	London		United Kingdom	SW3 6JJ
31	Novartis Investigative Site	Manchester		United Kingdom	M20 4BX