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

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

ClinicalTrials.gov Identifier: NCT03499899

Novartis Reference Number: CLAG525B2101

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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 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.

Condition 
Triple-negative Breast Cancer
Phase 
Phase 2
Overall status 
Active, not recruiting
Enrollment count 
88 participants
Start date 
Jul 02, 2018
Completion date 
Jan 25, 2021
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

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

Eligibility Criteria

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 from locally recurrent or metastatic site, 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)

Exclusion Criteria:

Patient has received prior immune checkpoint inhibitors 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 Locations

United States
Ironwood Cancer and Research Centers
-
Chandler, 85224
Arizona
United States
Highlands Oncology Group
-
Fayetteville, 72703
Arkansas
United States
Argentina
Novartis Investigative Site
-
Caba, C1280AEB
Buenos Aires
Argentina
Australia
Novartis Investigative Site
-
Wooloongabba, 4102
Queensland
Australia
Novartis Investigative Site
-
Melbourne, 3000
Victoria
Australia
Novartis Investigative Site
-
Nedlands, 6009
Western Australia
Australia
Belgium
Novartis Investigative Site
-
Liege, 4000
-
Belgium
Canada
Novartis Investigative Site
-
Montreal, H3T 1E2
Quebec
Canada
Novartis Investigative Site
-
Quebec, G1S 4L8
-
Canada
France
Novartis Investigative Site
-
Paris, 75231
-
France
Germany
Novartis Investigative Site
-
Luebeck, 23563
Schleswig-holstein
Germany
Novartis Investigative Site
-
Erlangen, 91054
-
Germany
Novartis Investigative Site
-
Tübingen, 72076
-
Germany
Hungary
Novartis Investigative Site
-
Budapest, H 1122
-
Hungary
Novartis Investigative Site
-
Szeged, H-6720
-
Hungary
Israel
Novartis Investigative Site
-
Tel Aviv, 6423906
-
Israel
Italy
Novartis Investigative Site
-
Napoli, 80131
-
Italy
Japan
Novartis Investigative Site
-
Nagoya-city, 467-8602
Aichi
Japan
Novartis Investigative Site
-
Nagoya, 466 8560
Aichi
Japan
Novartis Investigative Site
-
Yokohama-city, 241-8515
Kanagawa
Japan
Novartis Investigative Site
-
Minato ku, 105-8470
Tokyo
Japan
Korea, Republic of
Novartis Investigative Site
-
Seoul, 05505
Korea
Korea, Republic of
Novartis Investigative Site
-
Seoul, 03080
-
Korea, Republic of
Lebanon
Novartis Investigative Site
-
Ashrafieh, 166830
-
Lebanon
Novartis Investigative Site
-
El Metn,
-
Lebanon
Novartis Investigative Site
-
Saida, 652
-
Lebanon
Singapore
Novartis Investigative Site
-
Singapore, 169610
-
Singapore
Spain
Novartis Investigative Site
-
Sevilla, 41013
Andalucia
Spain
Novartis Investigative Site
-
Madrid, 28034
-
Spain
Taiwan
Novartis Investigative Site
-
Taipei, 10002
-
Taiwan
Novartis Investigative Site
-
Taipei, 11217
-
Taiwan
Novartis Investigative Site
-
Taipei,
-
Taiwan
Thailand
Novartis Investigative Site
-
Songkla, 90110
-
Thailand

Have a question?

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