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

• ClinicalTrials.gov Identifier: NCT03484923
• Recruitment Status: Completed
• First Posted: April 2, 2018
• Last Update Posted: January 30, 2023
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

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 (Clinical Trial)
• 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.
• 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: September 10, 2018
• Actual Primary Completion Date: December 30, 2022
• Actual Study Completion Date: December 30, 2022

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 Name: 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 Name: PDR001; Drug: Capmatinib; Taken orally; Other Name: 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 Name: PDR001; Drug: Canakinumab; Taken subcutaneusly (s.c); Other Name: 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 Name: PDR001; Drug: Ribociclib; Taken orally; Other Name: 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 Name: PDR001; Drug: LAG525; Taken intravenously (i.v)

Outcome Measures

Primary Outcome Measures :

1. Overall Response Rate (ORR) [ Time Frame: 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 :

1. Duration of Response [ Time Frame: 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)
2. Overall Survival (OS) [ Time Frame: 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
3. Progression Free Survival (PFS) [ Time Frame: 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)
4. Disease Control Rate (DCR) [ Time Frame: 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)
5. Prevalence of anti-drug antibodies (ADA) prevalence at baseline [ Time Frame: At Baseline ]
   Number of patients with presence of anti-drug antibodies (ADA)
6. Incidence of anti-drug antibodies (ADA) [ Time Frame: Throughout study until 150 day after last drug administration ]
   Number of patients developing new anti-drug antibodies (ADA)
7. Percentage of subjects with a favorable biomarker profile (pFBP) [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

The Angeles Clinic and Research Institute

Los Angeles, California, United States, 90025

University of California Los Angeles

Los Angeles, California, United States, 90095

UCSF Medical Center

San Francisco, California, United States, 94143

United States, Massachusetts

Massachusetts General Hospital Massachusetts Gen. Hospital CC

Boston, Massachusetts, United States, 02114

United States, New York

NYU Laura and Isaac Perlmutter Cancer Center Perlmutter Cancer Center

New York, New York, United States, 10016

United States, Pennsylvania

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States, 15232

Australia, New South Wales

Novartis Investigative Site

North Sydney, New South Wales, Australia, 2060

Novartis Investigative Site

Westmead, New South Wales, Australia, 2145

Canada, Ontario

Novartis Investigative Site

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

Novartis Investigative Site

Montreal, Quebec, Canada, H3T 1E2

France

Novartis Investigative Site

Marseille, France, 13009

Novartis Investigative Site

Paris Cedex 10, France, 75475

Novartis Investigative Site

Villejuif Cedex, France, 94800

Germany

Novartis Investigative Site

Dresden, Germany, 01307

Novartis Investigative Site

Essen, Germany, 45147

Novartis Investigative Site

Hamburg, Germany, 20246

Novartis Investigative Site

Kiel, Germany, 24105

Novartis Investigative Site

Muenchen, Germany, 81377

Italy

Novartis Investigative Site

Bergamo, BG, Italy, 24127

Novartis Investigative Site

Milano, MI, Italy, 20133

Novartis Investigative Site

Napoli, Italy, 80131

Netherlands

Novartis Investigative Site

Amsterdam, Netherlands, 1066 CX

Novartis Investigative Site

Rotterdam, Netherlands, 3015 GD

Spain

Novartis Investigative Site

Barcelona, Catalunya, Spain, 08036

Novartis Investigative Site

Hospitalet de LLobregat, Catalunya, Spain, 08907

Novartis Investigative Site

Madrid, Spain, 28009

Switzerland

Novartis Investigative Site

Zuerich, Switzerland, 8091

United Kingdom

Novartis Investigative Site

Northwood, Middlesex, United Kingdom, HA6 2RN

Novartis Investigative Site

London, United Kingdom, SW3 6JJ

Novartis Investigative Site

Manchester, United Kingdom, M20 4BX

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03484923
• Other Study ID Numbers: CPDR001J2201; 2018-000610-38 ( EudraCT Number )
• First Posted: April 2, 2018
• Last Update Posted: January 30, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

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.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Unresectable; melanoma; metastatic melanoma; advanced melanoma; spartalizumab; PDR001; LAG525; capmatinib; INC280; canakinumab; ACZ885; ribociclib; LEE011; immunotherapy; platform study; LAG-3

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Spartalizumab; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Immunological; Antineoplastic Agents