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
Condition: Triple-negative Breast Cancer
MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms
Intervention: LAG525; PDR001; Carboplatin
Intervention description: 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
Intervention MeSH terms: Carboplatin; Spartalizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 88.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: advanced triple-negative breast cancer; triple-negative breast cancer; checkpoint inhibition; LAG525; spartalizumab; PDR001; carboplatin

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.
    

Eligibility criteria:

        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)

        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