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Trial record 3 of 37 for:    PDR001 AND response rate

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 : July 19, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE March 26, 2018
First Posted Date  ICMJE April 17, 2018
Last Update Posted Date July 19, 2019
Actual Study Start Date  ICMJE July 2, 2018
Estimated Primary Completion Date March 27, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 6, 2018)
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 overall response rate (ORR) per investigator's assessment according to RECIST v1.1.
Original Primary Outcome Measures  ICMJE
 (submitted: April 9, 2018)
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.
Change History Complete list of historical versions of study NCT03499899 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2018)
  • 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
  • Overall Survival (OS) [ Time Frame: Up to death due to any cause (3 years) ]
    To assess Overall Survival for each treatment arm
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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 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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Triple-negative Breast Cancer
Intervention  ICMJE
  • 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.
    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.
Study Arms  ICMJE
  • Experimental: LAG525 + spartalizumab

    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).

    Interventions:
    • Drug: LAG525
    • Drug: spartalizumab
  • Experimental: LAG525+spartalizumab+carboplatin
    Patients in this arm will be given LAG525 plus spartalizumab plus carboplatin and approximately 32 patients will be randomized to this arm.
    Interventions:
    • Drug: LAG525
    • Drug: spartalizumab
    • Drug: carboplatin
  • Experimental: LAG525 + carboplatin
    Patients in this arm will be given LAG525 plus carboplatin and approximately 32 patients will be randomized to this arm.
    Interventions:
    • Drug: LAG525
    • Drug: carboplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 28, 2019)
84
Original Estimated Enrollment  ICMJE
 (submitted: April 9, 2018)
126
Estimated Study Completion Date  ICMJE November 6, 2020
Estimated Primary Completion Date March 27, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   France,   Germany,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Lebanon,   Singapore,   Spain,   Taiwan,   Thailand,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03499899
Other Study ID Numbers  ICMJE CLAG525B2101
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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.

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP