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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02460224




Registration number
NCT02460224
Ethics application status
Date submitted
9/05/2015
Date registered
2/06/2015
Date last updated
9/09/2020

Titles & IDs
Public title
Safety and Efficacy of LAG525 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies.
Scientific title
A Phase I/II, Open Label, Multicenter Study of the Safety and Efficacy of LAG525 Single Agent and in Combination With PDR001 Administered to Patients With Advanced Malignancies
Secondary ID [1] 0 0
CLAG525X2101C
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LAG525
Treatment: Drugs - PDR001

Experimental: Arm A - Single agent treatment arm with LAG525

Experimental: Arm B: combination of LAG525 and PDR001 - Combination treatment arm with LAG525 and PDR001

Experimental: Arm C - Single agent treatment arm with LAG525 in Japanese pts


Treatment: Drugs: LAG525
study drug 1

Treatment: Drugs: PDR001
study drug 2

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase I part: Incidence of dose limiting toxicities (DLTs) - A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment with single agent LAG525 or within the first two cycles of treatment with the combination of LAG525 and PDR001
Timepoint [1] 0 0
30 months
Primary outcome [2] 0 0
Phase II part: Overall response Rate per RECIST V1.1 - Overall Response Rate (ORR) is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) based on local Investigator assessment, as defined in RECIST v1.1. Estimation of the true ORR in this part of the study will be based upon the observed ORR for patients in full analysis set.
Timepoint [2] 0 0
30 months
Secondary outcome [1] 0 0
AUC - Characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001
Timepoint [1] 0 0
30 months
Secondary outcome [2] 0 0
Presence and/ or concentration of anti-LAG525 and anti-PDR001 antibodies - Assess emergence of anti-LAG525, and anti-PDR001 antibodies following one or more intravenous (i.v.) infusions of single agent LAG525 given alone or in combination with PDR001
Timepoint [2] 0 0
30 months
Secondary outcome [3] 0 0
Correlation of PD-L1, Lymphocyte activation gene-3 LAG-3 expression - Assess potential predictors of efficacy of single agent LAG525 and the combination of LAG525 and PDR001
Timepoint [3] 0 0
30 months
Secondary outcome [4] 0 0
Overall response Rate (ORR) - Evaluate the preliminary antitumor activity per RECIST as well as per immune related Response Criteria (irRC) on single agent LAG525 given alone or in combination with PDR001
Timepoint [4] 0 0
30 months
Secondary outcome [5] 0 0
Expression of IFN-? immune-related genes by mRNA profiling - Assess the pharmacodynamic effect of single agent LAG525 and the combination of LAG525 and PDR001
Timepoint [5] 0 0
30 months
Secondary outcome [6] 0 0
Safety incidence of Adverse Events (AEs - Characterize the safety of single agent LAG525 given alone and in combination with PDR001
Timepoint [6] 0 0
30 months
Secondary outcome [7] 0 0
Tolerability measured by dose interruptions - Characterize the tolerability of single agent LAG525 given alone and in combination with PDR001
Timepoint [7] 0 0
30 months
Secondary outcome [8] 0 0
Progression free survival (PFS) - Evaluate the preliminary antitumor activity per RECIST as well as per immune related Response Criteria (irRC) on single agent LAG525 given alone or in combination with PDR001
Timepoint [8] 0 0
30 months
Secondary outcome [9] 0 0
Duration of response (DOR) - Evaluate the preliminary antitumor activity per RECIST as well as per immune related Response Criteria (irRC) on single agent LAG525 given alone or in combination with PDR001
Timepoint [9] 0 0
30 months
Secondary outcome [10] 0 0
Disease control rate (DCR) - Evaluate the preliminary antitumor activity per RECIST as well as per immune related Response Criteria (irRC) on single agent LAG525 given alone or in combination of PDR001
Timepoint [10] 0 0
30 months
Secondary outcome [11] 0 0
Safety measuresd by incidence of Serious Adverse Events (SAEs) - Characterize the safety of single agent LAG525 given alone and in combination with PDR001
Timepoint [11] 0 0
30 months
Secondary outcome [12] 0 0
Cmax - Characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001
Timepoint [12] 0 0
30 months
Secondary outcome [13] 0 0
Tmax - Characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001
Timepoint [13] 0 0
30 months
Secondary outcome [14] 0 0
half-life - Characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001
Timepoint [14] 0 0
30 months
Secondary outcome [15] 0 0
Tolerability measured by dose reductions - Characterize the tolerability of single agent LAG525 given alone and in combination with PDR001
Timepoint [15] 0 0
30 months

Eligibility
Key inclusion criteria
Phase I part:

- Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease
as determined by RECIST version 1.1 (refer to Appendix 1), who have progressed despite
standard therapy or are intolerant of standard therapy, or for whom no standard therapy
exists

Phase II part:

- Patients with advanced/metastatic solid tumors, with at least one measurable lesion as
determined by RECIST version 1.1, who have had disease progression following their
last prior therapy and fit into one of the following groups:

- Group 1: NSCLC

- Group 2: Melanoma

- Group 3: Renal cancer

- Group 4: Mesothelioma

- Group 5: TNBC

- Eastern Cooperative Oncology Group (ECOG) Performance Status = 1

- Patient must have a site of disease amenable to biopsy, and be a candidate for tumor
biopsy.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of severe hypersensitivity reactions to study treatment ingredients or other
mAbs

- Active, known or suspected autoimmune disease

- Active infection requiring systemic antibiotic therapy

- HIV infection. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection

- Patients receiving chronic treatment with systemic steroid therapy, other than
replacement-dose corticosteroids in the setting of adrenal insufficiency

- Patients receiving systemic treatment with any immunosuppressive medication

- Use of live vaccines against infectious disease within 4 weeks of initiation of study
treatment

- Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment.

- Presence of symptomatic central nervous system (CNS) metastases or CNS metastases that
require local CNS-directed therapy or increasing doses of corticosteroids within the
prior 2 weeks

- History of drug-induced pneumonitis or current pneumonitis.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Westmead
Recruitment hospital [2] 0 0
Novartis Investigative Site - Heidelberg
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New York
Country [2] 0 0
United States of America
State/province [2] 0 0
North Carolina
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
United States of America
State/province [4] 0 0
Utah
Country [5] 0 0
Belgium
State/province [5] 0 0
Leuven
Country [6] 0 0
Canada
State/province [6] 0 0
Alberta
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
France
State/province [8] 0 0
Lyon Cedex
Country [9] 0 0
France
State/province [9] 0 0
Saint-Herblain Cédex
Country [10] 0 0
Germany
State/province [10] 0 0
Heidelberg
Country [11] 0 0
Germany
State/province [11] 0 0
Wuerzburg
Country [12] 0 0
Hong Kong
State/province [12] 0 0
Hong Kong
Country [13] 0 0
Italy
State/province [13] 0 0
MI
Country [14] 0 0
Italy
State/province [14] 0 0
MO
Country [15] 0 0
Japan
State/province [15] 0 0
Fukuoka
Country [16] 0 0
Singapore
State/province [16] 0 0
Singapore
Country [17] 0 0
Spain
State/province [17] 0 0
Catalunya
Country [18] 0 0
Spain
State/province [18] 0 0
Madrid
Country [19] 0 0
Taiwan
State/province [19] 0 0
Taipei

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

Ethics approval
Ethics application status

Summary
Brief summary
This study is to characterize the safety, tolerability, pharmacokinetics (PK),
pharmacodynamics (PD) and anti-tumor activity of LAG525 as a single agent and in combination
with PDR001 to adult patients with solid tumors. The study consists of a dose escalation
phase (I) to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D)
for LAG525 as a single agent and in combination with PDR001, and a dose expansion phase (II)
which will characterize treatment of LAG525 as a single agent and in combination with PDR001
at the MTD or RP2D.
Trial website
https://clinicaltrials.gov/show/NCT02460224
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

Summary results
Other publications