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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03499899
Ethics application status
Date submitted
26/03/2018
Date registered
17/04/2018

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
2017-004865-28
Secondary ID [2] 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 - PDR001
Treatment: Drugs - Carboplatin

Experimental: LAG525 + PDR001 - Participants received LAG525 and PDR001 administered as infusion once every 3 weeks

Experimental: LAG525 + PDR001 + carboplatin - Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.

Experimental: LAG525 + carboplatin - Participants received LAG525 and carboplatin administered as infusion once every 3 weeks


Treatment: Drugs: LAG525
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

Treatment: Drugs: PDR001
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

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

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (ORR) Per Investigator's Assessment According to RECIST v1.1
Timepoint [1] 0 0
Up to approximately 14 months
Secondary outcome [1] 0 0
Clinical Benefit Rate (CBR) Per Investigator's Assessment According to RECIST v1.1
Timepoint [1] 0 0
Up to approximately 14 months
Secondary outcome [2] 0 0
Duration of Response (DOR) Per Investigator's Assessment According to RECIST v1.1
Timepoint [2] 0 0
From first documented response up to disease progression or death due to underlying cancer, whichever occurs first, up to approximately 14 months
Secondary outcome [3] 0 0
Time to Response (TTR) Per Investigator's Assessment According to RECIST v1.1
Timepoint [3] 0 0
From date of randomization to first documented response (CR or PR), up to approximately 14 months
Secondary outcome [4] 0 0
Progression Free Survival (PFS)
Timepoint [4] 0 0
From date of randomization to disease progression or death due to any cause, whichever occurs first, up to approximately 14 months
Secondary outcome [5] 0 0
Overall Survival (OS)
Timepoint [5] 0 0
From date of randomization to date of death due to any cause, up to 18 months
Secondary outcome [6] 0 0
Pharmacokinetics (PK) Parameter, Area Under the Plasma Concentration Versus Time Curve From Time 0 to 504 Hours (AUC0-504h) of LAG525
Timepoint [6] 0 0
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
Secondary outcome [7] 0 0
PK Parameter, Cmax of LAG525
Timepoint [7] 0 0
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
Secondary outcome [8] 0 0
PK Parameter, AUClast of LAG525
Timepoint [8] 0 0
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
Secondary outcome [9] 0 0
PK Parameter, Tmax of LAG525
Timepoint [9] 0 0
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
Secondary outcome [10] 0 0
PK Parameter, AUC0-504h of PDR001
Timepoint [10] 0 0
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
Secondary outcome [11] 0 0
PK Parameter, Cmax of PDR001
Timepoint [11] 0 0
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
Secondary outcome [12] 0 0
PK Parameter, AUClast of PDR001
Timepoint [12] 0 0
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
Secondary outcome [13] 0 0
PK Parameter, Tmax of PDR001
Timepoint [13] 0 0
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
Secondary outcome [14] 0 0
PK Parameter, AUC0-4h of Carboplatin (Total Platinum)
Timepoint [14] 0 0
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
Secondary outcome [15] 0 0
PK Parameter, Cmax of Carboplatin (Total Platinum)
Timepoint [15] 0 0
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
Secondary outcome [16] 0 0
PK Parameter, AUClast of Carboplatin (Total Platinum)
Timepoint [16] 0 0
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
Secondary outcome [17] 0 0
PK Parameter, Tmax of Carboplatin (Total Platinum)
Timepoint [17] 0 0
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
Secondary outcome [18] 0 0
PK Parameter, AUC0-4h of Carboplatin (Ultrafilterable Platinum)
Timepoint [18] 0 0
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
Secondary outcome [19] 0 0
PK Parameter, Cmax of Carboplatin (Ultrafilterable Platinum)
Timepoint [19] 0 0
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
Secondary outcome [20] 0 0
PK Parameter, AUClast of Carboplatin (Ultrafilterable Platinum)
Timepoint [20] 0 0
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
Secondary outcome [21] 0 0
PK Parameter, Tmax of Carboplatin (Ultrafilterable Platinum)
Timepoint [21] 0 0
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
Secondary outcome [22] 0 0
Number of Participants With Anti-drug Antibodies (ADA) at Baseline for LAG525
Timepoint [22] 0 0
Baseline
Secondary outcome [23] 0 0
Number of Participants With Anti-drug Antibodies (ADA) on Treatment for LAG525
Timepoint [23] 0 0
From Cycle 1 to Cycle 7 (Day 1 pre-infusion) and end of treatment, assessed up to 3 years
Secondary outcome [24] 0 0
Number of Participants With Anti-drug Antibodies (ADA) at Baseline for PDR001
Timepoint [24] 0 0
Baseline
Secondary outcome [25] 0 0
Number of Participants With Anti-drug Antibodies (ADA) on Treatment for PDR001
Timepoint [25] 0 0
From Cycle 1 to Cycle 7 (Day 1 pre-infusion) and end of treatment, assessed up to 2.8 years

Eligibility
Key inclusion criteria
* 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)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/07/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/11/2021
Sample size
Target
Accrual to date
Final
88
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
Argentina
State/province [3] 0 0
Buenos Aires
Country [4] 0 0
Belgium
State/province [4] 0 0
Liege
Country [5] 0 0
Canada
State/province [5] 0 0
Quebec
Country [6] 0 0
France
State/province [6] 0 0
Paris
Country [7] 0 0
Germany
State/province [7] 0 0
Schleswig-holstein
Country [8] 0 0
Germany
State/province [8] 0 0
Erlangen
Country [9] 0 0
Germany
State/province [9] 0 0
Tübingen
Country [10] 0 0
Hungary
State/province [10] 0 0
Budapest
Country [11] 0 0
Hungary
State/province [11] 0 0
Szeged
Country [12] 0 0
Israel
State/province [12] 0 0
Tel Aviv
Country [13] 0 0
Italy
State/province [13] 0 0
Napoli
Country [14] 0 0
Japan
State/province [14] 0 0
Aichi
Country [15] 0 0
Japan
State/province [15] 0 0
Kanagawa
Country [16] 0 0
Japan
State/province [16] 0 0
Tokyo
Country [17] 0 0
Korea, Republic of
State/province [17] 0 0
Korea
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Seoul
Country [19] 0 0
Lebanon
State/province [19] 0 0
Ashrafieh
Country [20] 0 0
Lebanon
State/province [20] 0 0
El Metn
Country [21] 0 0
Lebanon
State/province [21] 0 0
Saida
Country [22] 0 0
Singapore
State/province [22] 0 0
Singapore
Country [23] 0 0
Spain
State/province [23] 0 0
Andalucia
Country [24] 0 0
Spain
State/province [24] 0 0
Madrid
Country [25] 0 0
Taiwan
State/province [25] 0 0
Taipei
Country [26] 0 0
Thailand
State/province [26] 0 0
Songkla

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03499899