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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03499899




Registration number
NCT03499899
Ethics application status
Date submitted
26/03/2018
Date registered
9/04/2018
Date last updated
7/02/2019

Titles & IDs
Public title
A Study of Efficacy and Safety of LAG525 in Combination With Spartalizumab, or With Spartalizumab and Carboplatin, or With Carboplatin, in Patients With Advanced Triple-negative Breast Cancer
Scientific title
A Phase II Open-label, Randomized, Three-arm, Multicenter Study of LAG525 Given in Combination With Spartalizumab (PDR001), or With Spartalizumab and Carboplatin, or With Carboplatin, as First or Second Line Therapy in Patients With Advanced Triple-negative Breast Cancer
Secondary ID [1] 0 0
CLAG525B2101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Triple-negative Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

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

Experimental: LAG525 + spartalizumab - Patients in this arm will be given LAG525 plus spartalizumab and approximately 32 patients will be randomized to this arm

Experimental: LAG525+spartalizumab+carboplatin - Patients in this arm will be given LAG525 plus spartalizumab plus carboplatin and approximately 32 patients will be randomized to this arm.

Experimental: LAG525 + carboplatin - Patients in this arm will be given LAG525 plus carboplatin and approximately 32 patients will be randomized to this arm.


Treatment: Drugs: LAG525
LAG525, a concentrate for solution for intravenous infusion, comes in 100mg vials as a liquid formulation for infusion and is dosed at 400mg every 21 days.

Treatment: Drugs: spartalizumab
Spartalizumab is a concentrate for solution for intravenous infusion, comes in 100mg vials as a liquid formulation for infusion and is dosed at 300mg every 21 days.

Treatment: Drugs: carboplatin
Carboplatin is a concentrate for solution for intravenous infusion, comes in 100mg/mL and is dosed per AUC 6 every 21 days.

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

Outcomes
Primary outcome [1] 0 0
Overall response rate (ORR) per RECIST v1.1 per investigators' assessment - To assess the antitumor activity of the three treatment arms LAG525 + spartalizumab, LAG525 + spartalizumab + carboplatin and LAG525 + carboplatin, in subjects with advanced TNBC in first or second line therapy, as measured by the overall response rate (ORR) per investigator's assessment according to RECIST v1.1.
Timepoint [1] 0 0
24 months
Secondary outcome [1] 0 0
Duration of response (DOR) - To assess the efficacy of the three treatment arms with respect to DOR per investigator's assessment according to RECIST v1.1
Timepoint [1] 0 0
Up to disease progression or death due to any cause, whichever occurs first (3 years)
Secondary outcome [2] 0 0
Overall Survival (OS) - To assess Overall Survival for each treatment arm
Timepoint [2] 0 0
Up to death due to any cause (3 years)
Secondary outcome [3] 0 0
Pharmacokinetics (PK) parameter, Ctrough, of LAG525, spartalizumab and carboplatin - To characterize the PK parameter, Ctrough, of LAG525, spartalizumab, and carboplatin in the three investigated combinations
Timepoint [3] 0 0
Up to cycle 7 (each cycle is 21 days) and at end of treatment (up to 3 years)
Secondary outcome [4] 0 0
Time to response (TTR) - To assess the efficacy of the three treatment arms with respect to TTR per investigator's assessment according to RECIST v1.1
Timepoint [4] 0 0
Up to death due to any cause (3 years)
Secondary outcome [5] 0 0
Progression free survival (PFS) - To assess the efficacy of the three treatment arms with respect to PFS per investigator's assessment according to RECIST v1.1
Timepoint [5] 0 0
Up to disease progression or death due to any cause, whichever occurs first (3 years)
Secondary outcome [6] 0 0
Clinical Benefit Rate (CBR) - To assess the efficacy of the three treatment arms with respect to CBR per investigator's assessment according to RECIST v1.1
Timepoint [6] 0 0
24 months
Secondary outcome [7] 0 0
PK parameter, Cmax of LAG525, spartalizumab and carboplatin - To characterize the PK parameter, Cmax, of LAG525, spartalizumab, and carboplatin in the three investigated combinations
Timepoint [7] 0 0
Up to cycle 7 (each cycle is 21 days)
Secondary outcome [8] 0 0
PK parameter, AUC, of LAG525, spartalizumab and carboplatin - To characterize the PK parameter, AUC, of LAG525, spartalizumab, and carboplatin in the three investigated combinations
Timepoint [8] 0 0
Up to cycle 7 (each cycle is 21 days) and at end of treatment (up to 3 years)
Secondary outcome [9] 0 0
Anti-drug antibodies (ADA) prevalence at baseline for LAG525 and spartalizumab - To assess immunogenicity of LAG525 and spartalizumab in the three investigated combinations
Timepoint [9] 0 0
At baseline
Secondary outcome [10] 0 0
Anti-drug antibodies (ADA) incidence on treatment for LAG525 and spartalizumab - To assess immunogenicity of LAG525 and spartalizumab in the three investigated combinations
Timepoint [10] 0 0
Throughout study until 150 days after last drug administration

Eligibility
Key inclusion criteria
- Patient has advanced (loco-regionally recurrent not amenable to curative therapy or
metastatic) breast cancer.

- Patient must have measurable disease, i.e., at least one measurable lesion as per
RECIST 1.1 criteria (Tumor lesions previously irradiated or subjected to other
loco-regional therapy will only be considered measurable if disease progression at the
treated site after completion of therapy is clearly documented)

- Patient progressed after adjuvant or 1 prior systemic treatment in the metastatic
setting. Patients with de novo metastatic disease are eligible if they received 1
prior line of therapy

- Patient must have received prior systemic treatment that included taxane-based
chemotherapy for adjuvant or metastatic disease

- Patient must have a site of disease amenable to biopsy, and must be willing to undergo
a new tumor biopsy at screening and during therapy on this study, the latter if
medically feasible. Patients with an available archival tumor tissue do not need to
perform a tumor biopsy at screening if patient has not received anti-cancer therapy
since the biopsy was taken.

- Patient has histologically and/or cytologically confirmed diagnosis of advanced TNBC
(based on most recently analyzed biopsy, local lab) meeting the following criteria:
HER2 negative in situ hybridization test or an IHC status of 0 or 1+, and ER and PR
expression is <1 percent as determined by immunohistochemistry (IHC)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patient has received prior immunotherapy as anticancer treatment such as anti-LAG-3,
anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody (any line of therapy).

- Patient received prior neoadjuvant or adjuvant therapy with a platinum agent or
mitomycin and experienced recurrence within 12 months after the end of the
platinum-based or mitomycin containing therapy or received Platinum or mitomycin for
metastatic disease

- Patient has had major surgery within 14 days prior to starting study treatment or has
not recovered to grade 1 or less from major side effects.

- Patient with presence of CTCAE grade 2 toxicity or higher due to prior cancer therapy.
Exception to this criterion; patients with any grade of alopecia are allowed to enter
the study..

- Patient has received radiotherapy = 4 weeks prior to randomization (= 2 weeks for
limited field radiation for palliation), and has not recovered to grade 1 or better
from related side effects of such therapy (with the exception of alopecia).

- Patient has a known hypersensitivity to other monoclonal antibodies,
platinum-containing compounds, or to any of the excipients of LAG525, spartalizumab,
or carboplatin.

- Patient has symptomatic central nervous system (CNS) metastases or CNS metastases that
require local CNS-directed therapy (such as radiotherapy or surgery), or increasing
doses of corticosteroids within the 2 weeks prior to first dose of study treatment.
Patients with treated brain metastases should be neurologically stable and witout CNS
progression for at least 12 weeks prior to randomization and have discontinued
corticosteroid treatment (with the exception of < 10 mg/day of prednisone or
equivalent for an indication other than CNS metastases) for at least 4 weeks before
first dose of any study treatment.

Other protocol-defined inclusion/exclusion criteria may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
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)
QLD,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Wooloongabba
Recruitment hospital [2] 0 0
Novartis Investigative Site - Melbourne
Recruitment hospital [3] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
4102 - Wooloongabba
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
Belgium
State/province [3] 0 0
Liege
Country [4] 0 0
Belgium
State/province [4] 0 0
Sint Niklaas
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario
Country [6] 0 0
Canada
State/province [6] 0 0
Quebec
Country [7] 0 0
Germany
State/province [7] 0 0
Schleswig-holstein
Country [8] 0 0
Germany
State/province [8] 0 0
Dresden
Country [9] 0 0
Germany
State/province [9] 0 0
Essen
Country [10] 0 0
Germany
State/province [10] 0 0
Tuebingen
Country [11] 0 0
Hungary
State/province [11] 0 0
Budapest
Country [12] 0 0
Hungary
State/province [12] 0 0
Szeged
Country [13] 0 0
Israel
State/province [13] 0 0
Ramat Gan
Country [14] 0 0
Italy
State/province [14] 0 0
MI
Country [15] 0 0
Italy
State/province [15] 0 0
PN
Country [16] 0 0
Italy
State/province [16] 0 0
Napoli
Country [17] 0 0
Japan
State/province [17] 0 0
Aichi
Country [18] 0 0
Japan
State/province [18] 0 0
Kanagawa
Country [19] 0 0
Japan
State/province [19] 0 0
Tokyo
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Korea
Country [21] 0 0
Korea, Republic of
State/province [21] 0 0
Seoul
Country [22] 0 0
Lebanon
State/province [22] 0 0
Ashrafieh
Country [23] 0 0
Lebanon
State/province [23] 0 0
El Metn
Country [24] 0 0
Lebanon
State/province [24] 0 0
Saida
Country [25] 0 0
Singapore
State/province [25] 0 0
Singapore
Country [26] 0 0
Spain
State/province [26] 0 0
Andalucia
Country [27] 0 0
Spain
State/province [27] 0 0
Catalunya
Country [28] 0 0
Spain
State/province [28] 0 0
Madrid
Country [29] 0 0
Taiwan
State/province [29] 0 0
Taipei
Country [30] 0 0
Thailand
State/province [30] 0 0
Bangkok
Country [31] 0 0
Thailand
State/province [31] 0 0
Chiang Mai
Country [32] 0 0
Thailand
State/province [32] 0 0
Songkla

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

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to assess the efficacy, safety, and PK characteristics of the
following three combinations: i) LAG525 + spartalizumab; ii) LAG525 + spartalizumab +
carboplatin, and iii) LAG525 + carboplatin in subjects with advanced TNBC and up to one prior
line of systemic treatment for metastatic disease. A thorough biomarker strategy to address
key aspects of tumor immunogenicity will be implemented in the study.

LAG525 and spartalizumab are two immuno-agents targeting different immune checkpoints, and
have been tested as single agents and in combination. To further enhance the efficacy of
checkpoint inhibition, carboplatin will be given with LAG525 or with LAG525 and
spartalizumab, based on the observation that the addition of chemotherapy can change the
tumor microenvironment to be more favorable to immune response.
Trial website
https://clinicaltrials.gov/show/NCT03499899
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
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
novartis.email@novartis.com
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable