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

Phase 2

• Conditions: Triple Negative Breast Cancer; Tripple negative ABC; C50.9

• Registration Number: LBCTR2019020196
• Lead Sponsor: ovartis Pharma Services Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Completion: 2019-09-13
• Study Start: 2022-06-29
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Complete
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

1-Patient has advanced (loco-regionally recurrent not amenable to curative therapy or metastatic) breast cancer.
2-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)
3-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
4-Patient must have received prior systemic treatment that included taxane-based chemotherapy for adjuvant or metastatic disease
5-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.
6-Patient has histologically and/or cytologically confirmed diagnosis of advanced 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

1-Patient has received prior immunotherapy as anticancer treatment such as anti-LAG-3, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody (any line of therapy).
2-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
3-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.
4-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..
5-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).
6-Patient has a known hypersensitivity to other monoclonal antibodies, platinum-containing compounds, or to any of the excipients of LAG525, spartalizumab, or carboplatin.
7-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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
ame: Overall response rate (ORR) per RECIST v1.1 per investigators' assessment;Timepoints: 24 months;Measure: 24 Months

Secondary Outcome Measures

Name	Time	Method
ame: Duration of response (DOR);Timepoints: 3 years;Measure: 3 years;Name: Overall Survival (OS);Timepoints: 3 years;Measure: 3 years;Name: Clinical Benefit Rate (CBR);Timepoints: 24 months;Measure: 24 months