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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

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ClinicalTrials.gov Identifier: NCT03499899
Recruitment Status : Recruiting
First Posted : April 17, 2018
Last Update Posted : October 22, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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 metastatic 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 or disease Intervention/treatment Phase
Triple-negative Breast Cancer Drug: LAG525 Drug: spartalizumab Drug: carboplatin Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 2, 2018
Estimated Primary Completion Date : December 26, 2019
Estimated Study Completion Date : December 8, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Carboplatin

Arm Intervention/treatment
Experimental: LAG525 + spartalizumab
approximately 32 patients will be randomized in this arm
Drug: LAG525
LAG525 is a concentrate for solution for intravenous infusion Intravenous use, 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.
Other Name: PDR001

Experimental: LAG525+spartalizumab+carboplatin
approximately 32 patients will be randomized in this arm
Drug: LAG525
LAG525 is a concentrate for solution for intravenous infusion Intravenous use, 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.
Other Name: PDR001

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

Experimental: LAG525 + carboplatin
approximately 32 patients will be randomized in this arm
Drug: LAG525
LAG525 is a concentrate for solution for intravenous infusion Intravenous use, comes in 100mg vials as a liquid formulation for infusion and is dosed at 400mg 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.




Primary Outcome Measures :
  1. Overall response rate (ORR) per RECIST v1.1 per investigators' assessment [ Time Frame: 24 months ]
    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 objective response rate (ORR) per investigator's assessment according to RECIST v1.1.


Secondary Outcome Measures :
  1. Duration of response (DOR) [ Time Frame: Up to disease progression or death due to any cause, whichever occurs first (3 years) ]
    To assess the efficacy of the three treatment arms with respect to DOR per investigator's assessment according to RECIST v1.1

  2. Overall Survival (OS) [ Time Frame: Up to death due to any cause (3 years) ]
    To assess Overall Survival for each treatment arm

  3. 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) ]
    To characterize the PK parameter, Ctrough, of LAG525, spartalizumab, and carboplatin in the three investigated combinations

  4. Time to response (TTR) [ Time Frame: Up to death due to any cause (3 years) ]
    To assess the efficacy of the three treatment arms with respect to TTR per investigator's assessment according to RECIST v1.1

  5. Progression free survival (PFS) [ Time Frame: Up to disease progression or death due to any cause, whichever occurs first (3 years) ]
    To assess the efficacy of the three treatment arms with respect to PFS per investigator's assessment according to RECIST v1.1

  6. Clinical Benefit Rate (CBR) [ Time Frame: 24 months ]
    To assess the efficacy of the three treatment arms with respect to CBR per investigator's assessment according to RECIST v1.1

  7. PK parameter, Cmax of LAG525, spartalizumab and carboplatin [ Time Frame: Up to cycle 7 (each cycle is 21 days) ]
    To characterize the PK parameter, Cmax, of LAG525, spartalizumab, and carboplatin in the three investigated combinations

  8. 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) ]
    To characterize the PK parameter, AUC, of LAG525, spartalizumab, and carboplatin in the three investigated combinations

  9. Anti-drug antibodies (ADA) prevalence at baseline for LAG525 and spartalizumab [ Time Frame: At baseline ]
    To assess immunogenicity of LAG525 and spartalizumab in the three investigated combinations

  10. Anti-drug antibodies (ADA) incidence on treatment for LAG525 and spartalizumab [ Time Frame: Throughout study until 150 days after last drug administration ]
    To assess immunogenicity of LAG525 and spartalizumab in the three investigated combinations



Information from the National Library of Medicine

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

Exclusion Criteria:

  • Patient has received prior treatment with anti-LAG-3, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody (any line of therapy).
  • Patient received prior therapy with a platinum agent or mitomycin and experienced recurrence within 12 months after the end of the platinum-based or mitomycin containing therapy
  • 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 (except alopecia, peripheral neuropathy and ototoxicity, which are excluded if ≥ CTCAE grade 3) due to prior cancer therapy.
  • 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 with history or presence of central nervous system (CNS) metastases, treated or untreated.

Other protocol-defined inclusion/exclusion criteria may apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03499899


Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
United States, Arkansas
Highlands Oncology Group Recruiting
Fayetteville, Arkansas, United States, 72703
Contact    479-936-9900      
Principal Investigator: Joseph T. Beck         
Australia, Queensland
Novartis Investigative Site Recruiting
Wooloongabba, Queensland, Australia, 4102
Australia, Victoria
Novartis Investigative Site Recruiting
Melbourne, Victoria, Australia, 3000
Australia, Western Australia
Novartis Investigative Site Recruiting
Nedlands, Western Australia, Australia, 6009
Belgium
Novartis Investigative Site Recruiting
Liege, Belgium, 4000
Canada
Novartis Investigative Site Recruiting
Quebec, Canada, G1S 4L8
Korea, Republic of
Novartis Investigative Site Recruiting
Seoul, Korea, Republic of, 03080
Lebanon
Novartis Investigative Site Recruiting
El Metn, Lebanon
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 169610
Taiwan
Novartis Investigative Site Recruiting
Taipei, Taiwan, 10002
Novartis Investigative Site Recruiting
Taipei, Taiwan, 11217
Novartis Investigative Site Recruiting
Taipei, Taiwan
Thailand
Novartis Investigative Site Recruiting
Bangkok, Thailand, 10310
Novartis Investigative Site Recruiting
Chiang Mai, Thailand, 50200
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03499899     History of Changes
Other Study ID Numbers: CLAG525B2101
First Posted: April 17, 2018    Key Record Dates
Last Update Posted: October 22, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
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 ):
triple-negative breast cancer
checkpoint inhibition
LAG525
spartalizumab
PDR001
carboplatin

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carboplatin
Antineoplastic Agents