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
2 other identifiers
interventional
88
17 countries
33
Brief Summary
The main purpose of this study was to assess the antitumor activity of three combinations: i) LAG525 + spartalizumab; ii) LAG525 + spartalizumab + carboplatin, and iii) LAG525 + carboplatin in participants with advanced triple-negative breast cancer (TNBC) in first or second line therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jul 2018
Typical duration for phase_2
33 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 26, 2018
CompletedFirst Posted
Study publicly available on registry
April 17, 2018
CompletedStudy Start
First participant enrolled
July 2, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 27, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
November 24, 2021
CompletedResults Posted
Study results publicly available
May 13, 2022
CompletedJanuary 30, 2023
January 1, 2023
1.7 years
March 26, 2018
April 20, 2022
January 27, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Response Rate (ORR) Per Investigator's Assessment According to RECIST v1.1
Overall response rate (ORR) is defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1 based on investigator's assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Up to approximately 14 months
Secondary Outcomes (25)
Clinical Benefit Rate (CBR) Per Investigator's Assessment According to RECIST v1.1
Up to approximately 14 months
Duration of Response (DOR) Per Investigator's Assessment According to RECIST v1.1
From first documented response up to disease progression or death due to underlying cancer, whichever occurs first, up to approximately 14 months
Time to Response (TTR) Per Investigator's Assessment According to RECIST v1.1
From date of randomization to first documented response (CR or PR), up to approximately 14 months
Progression Free Survival (PFS)
From date of randomization to disease progression or death due to any cause, whichever occurs first, up to approximately 14 months
Overall Survival (OS)
From date of randomization to date of death due to any cause, up to 18 months
- +20 more secondary outcomes
Study Arms (3)
LAG525 + PDR001
EXPERIMENTALParticipants received LAG525 and PDR001 administered as infusion once every 3 weeks
LAG525 + PDR001 + carboplatin
EXPERIMENTALParticipants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
LAG525 + carboplatin
EXPERIMENTALParticipants received LAG525 and carboplatin administered as infusion once every 3 weeks
Interventions
LAG525 was a concentrate for solution for intravenous infusion, came in 100mg vials as a liquid formulation for infusion and was dosed at 400mg every 21 days. For all arms, LAG525 was infused first
Spartalizumab was a concentrate for solution for intravenous infusion, came in 100mg vials as a liquid formulation for infusion and was dosed at 300mg every 21 days. Spartalizumab was infused after LAG525
Carboplatin was a concentrate for solution for intravenous infusion, came in 100mg/mL and was dosed per area under the curve (AUC) 6 every 21 days. Carboplatin was infused once LAG525 and spartalizumab infusions were completed
Eligibility Criteria
You may qualify if:
- Had advanced (loco-regionally recurrent not amenable to curative therapy or metastatic) breast cancer
- Had adequate bone marrow and organ function.
- Had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Had 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 was to be considered measurable if disease progression at the treated site after completion of therapy is clearly documented)
- Progressed after adjuvant or 1 prior systemic treatment in the metastatic setting. Patients with de novo metastatic disease were eligible if they received 1 prior line of therapy
- Had received prior systemic treatment that included taxane-based chemotherapy for adjuvant or metastatic disease
- Had a site of disease amenable to biopsy, and was 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 did not need to perform a tumor biopsy at screening if patient had not received anti-cancer therapy since the biopsy was taken.
- Had 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 was \<1 percent as determined by immunohistochemistry (IHC)
You may not qualify if:
- Had 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)
- 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
- Had major surgery within 14 days prior to starting study treatment or had not recovered to grade 1 or less from major side effects
- Presence of CTCAE grade 2 toxicity or higher due to prior cancer therapy. Exception to this criterion; patients with any grade of alopecia were allowed to enter the study.
- Had received radiotherapy ≤ 4 weeks prior to randomization (≤ 2 weeks for limited field radiation for palliation), and had not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia)
- Had a known hypersensitivity to other monoclonal antibodies, platinum-containing compounds, or to any of the excipients of LAG525, spartalizumab, or carboplatin
- Had symptomatic central nervous system (CNS) metastases or CNS metastases that required 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 would be neurologically stable and without CNS progression for at least 12 weeks prior to randomization and had 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
- Had clinically significant cardiac disease or impaired cardiac function
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (33)
Ironwood Cancer and Research Centers
Chandler, Arizona, 85224, United States
Highlands Oncology Group
Fayetteville, Arkansas, 72703, United States
Novartis Investigative Site
Caba, Buenos Aires, C1280AEB, Argentina
Novartis Investigative Site
Wooloongabba, Queensland, 4102, Australia
Novartis Investigative Site
Melbourne, Victoria, 3000, Australia
Novartis Investigative Site
Nedlands, Western Australia, 6009, Australia
Novartis Investigative Site
Liège, 4000, Belgium
Novartis Investigative Site
Montreal, Quebec, H3T 1E2, Canada
Novartis Investigative Site
Québec, G1S 4L8, Canada
Novartis Investigative Site
Paris, 75231, France
Novartis Investigative Site
Lübeck, Schleswig-Holstein, 23563, Germany
Novartis Investigative Site
Erlangen, 91054, Germany
Novartis Investigative Site
Tübingen, 72076, Germany
Novartis Investigative Site
Budapest, H 1122, Hungary
Novartis Investigative Site
Szeged, H-6720, Hungary
Novartis Investigative Site
Tel Aviv, 6423906, Israel
Novartis Investigative Site
Napoli, 80131, Italy
Novartis Investigative Site
Nagoya, Aichi-ken, 466 8560, Japan
Novartis Investigative Site
Nagoya, Aichi-ken, 467-8602, Japan
Novartis Investigative Site
Yokohama, Kanagawa, 241-8515, Japan
Novartis Investigative Site
Minato Ku, Tokyo, 105-8470, Japan
Novartis Investigative Site
El Achrafiyé, 166830, Lebanon
Novartis Investigative Site
El Metn, Lebanon
Novartis Investigative Site
Saida, 652, Lebanon
Novartis Investigative Site
Singapore, 169610, Singapore
Novartis Investigative Site
Seoul, Korea, 05505, South Korea
Novartis Investigative Site
Seoul, 03080, South Korea
Novartis Investigative Site
Seville, Andalusia, 41013, Spain
Novartis Investigative Site
Madrid, 28034, Spain
Novartis Investigative Site
Taipei, 10002, Taiwan
Novartis Investigative Site
Taipei, 11217, Taiwan
Novartis Investigative Site
Taipei, Taiwan
Novartis Investigative Site
Songkhla, 90110, Thailand
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 26, 2018
First Posted
April 17, 2018
Study Start
July 2, 2018
Primary Completion
February 27, 2020
Study Completion
November 24, 2021
Last Updated
January 30, 2023
Results First Posted
May 13, 2022
Record last verified: 2023-01
Data Sharing
- IPD Sharing
- Will share
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.