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.
Title
- Brief 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
- Official 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
Clinical Trial IDs
- ORG STUDY ID:
CLAG525B2101
- NCT ID:
NCT03499899
Conditions
- Triple-negative Breast Cancer
Interventions
Drug | Synonyms | Arms |
---|
LAG525 | | LAG525 + carboplatin |
spartalizumab | PDR001 | LAG525 + spartalizumab |
carboplatin | | LAG525 + carboplatin |
Purpose
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.
Detailed Description
The sponsor and the study steering committee decided to prematurely stop enrollment of
subjects to Arm 1 after data review showed an increased treatment discontinuation rate due to
progressive disease in Arm 1 as compared to Arms 2 and 3 (both containing Carboplatin).
Trial Arms
Name | Type | Description | Interventions |
---|
LAG525 + spartalizumab | Experimental | Patients in this arm were given LAG525 plus spartalizumab and approximately 20 patients were randomized to this arm.
The sponsor and the study steering committee decided to prematurely stop enrollment of subjects to Arm 1 after data review showed an increased treatment discontinuation rate due to progressive disease in Arm 1 as compared to Arms 2 and 3 (both containing Carboplatin). | |
LAG525+spartalizumab+carboplatin | Experimental | Patients in this arm will be given LAG525 plus spartalizumab plus carboplatin and approximately 32 patients will be randomized to this arm. | - LAG525
- spartalizumab
- carboplatin
|
LAG525 + carboplatin | Experimental | Patients in this arm will be given LAG525 plus carboplatin and approximately 32 patients will be randomized to this arm. | |
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Overall response rate (ORR) per RECIST v1.1 per investigators' assessment |
Time Frame: | 24 months |
Safety Issue: | |
Description: | 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. |
Secondary Outcome Measures
Measure: | Duration of response (DOR) |
Time Frame: | Up to disease progression or death due to any cause, whichever occurs first (3 years) |
Safety Issue: | |
Description: | To assess the efficacy of the three treatment arms with respect to DOR per investigator's assessment according to RECIST v1.1 |
Measure: | Overall Survival (OS) |
Time Frame: | Up to death due to any cause (3 years) |
Safety Issue: | |
Description: | To assess Overall Survival for each treatment arm |
Measure: | Pharmacokinetics (PK) parameter, Ctrough, of LAG525, spartalizumab and carboplatin |
Time Frame: | Up to cycle 7 (each cycle is 21 days) and at end of treatment (up to 3 years) |
Safety Issue: | |
Description: | To characterize the PK parameter, Ctrough, of LAG525, spartalizumab, and carboplatin in the three investigated combinations |
Measure: | Time to response (TTR) |
Time Frame: | Up to death due to any cause (3 years) |
Safety Issue: | |
Description: | To assess the efficacy of the three treatment arms with respect to TTR per investigator's assessment according to RECIST v1.1 |
Measure: | Progression free survival (PFS) |
Time Frame: | Up to disease progression or death due to any cause, whichever occurs first (3 years) |
Safety Issue: | |
Description: | To assess the efficacy of the three treatment arms with respect to PFS per investigator's assessment according to RECIST v1.1 |
Measure: | Clinical Benefit Rate (CBR) |
Time Frame: | 24 months |
Safety Issue: | |
Description: | To assess the efficacy of the three treatment arms with respect to CBR per investigator's assessment according to RECIST v1.1 |
Measure: | PK parameter, Cmax of LAG525, spartalizumab and carboplatin |
Time Frame: | Up to cycle 7 (each cycle is 21 days) |
Safety Issue: | |
Description: | To characterize the PK parameter, Cmax, of LAG525, spartalizumab, and carboplatin in the three investigated combinations |
Measure: | PK parameter, AUC, of LAG525, spartalizumab and carboplatin |
Time Frame: | Up to cycle 7 (each cycle is 21 days) and at end of treatment (up to 3 years) |
Safety Issue: | |
Description: | To characterize the PK parameter, AUC, of LAG525, spartalizumab, and carboplatin in the three investigated combinations |
Measure: | Anti-drug antibodies (ADA) prevalence at baseline for LAG525 and spartalizumab |
Time Frame: | At baseline |
Safety Issue: | |
Description: | To assess immunogenicity of LAG525 and spartalizumab in the three investigated combinations |
Measure: | Anti-drug antibodies (ADA) incidence on treatment for LAG525 and spartalizumab |
Time Frame: | Throughout study until 150 days after last drug administration |
Safety Issue: | |
Description: | To assess immunogenicity of LAG525 and spartalizumab in the three investigated combinations |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- advanced triple-negative breast cancer
- triple-negative breast cancer
- checkpoint inhibition
- LAG525
- spartalizumab
- PDR001
- carboplatin
Last Updated
August 31, 2021