phase ii study evaluating the efficacy and safety of ociperlimab in combination with tislelizumab and chemotherapy as first-line treatment for participants with advanced triple negative breast cancer

Conditions: Triple Negative Breast Cancer

Summary: the primary scientific question of interest of this study is whether the combination of ociperlimab, tislelizumab and chemotherapy improves progression-free survival (pfs) compared to the combination of placebo, pembrolizumab and chemotherapy as first-line therapy for adult men and women with advanced triple negative breast cancer (tnbc) whose tumors express programmed death ligand 1 (pd - l1) \[combined positive score (cps) ≥10\], regardless of study treatment discontinuation or start of new anti-neoplastic therapy.

this is a randomized, double-blind, placebo-controlled, multicenter, phase ii study evaluating the efficacy and safety of ociperlimab in combination with tislelizumab and chemotherapy as first-line treatment for participants with advanced tnbc whose tumors express pd-l1 (cps ≥ 10). additionally, the efficacy and safety of the triple combination (ociperlimab + tislelizumab + chemotherapy) will be assessed in arm d (a separate single-arm, open-label cohort) in 30 participants with advanced tnbc whose tumors express pd-l1 (cps ≥ 1 to \< 10). study treatment will continue until the participant experiences one of the following: disease progression per investigator's assessment by response evaluation criteria in solid tumors (recist) 1.1, unacceptable toxicity, pregnancy, treatment is discontinued at the discretion of the investigator or participant, start of a new antineoplastic therapy, withdrawal of consent, lost to follow-up, death, or study is terminated by the sponsor.

Eligibility criteria:
key inclusion criteria: * participant has histologically confirmed diagnosis of advanced (loco-regionally recurrent and not amenable to curative therapy, or metastatic (stage iv)) tnbc * participant has completed systemic treatment for stage i-iii breast cancer, if indicated, and ≥ 6 months have elapsed between the completion of systemic treatment with curative intent and disease recurrence * a recently or newly obtained tumor biopsy from a metastatic site must be provided for determination of pd-l1 expression using the pd-l1 ihc 22c3 assay by a novartis designated central laboratory, prior to study randomization. if a result of pd-l1 expression assessed by a pd-l1 ihc 22c3 pharmdx test in a local laboratory is available, this can serve as pd-l1 status confirmation. for arms a, b and c participants must have pd-l1 positive tumors with cps≥ 10. for arm d, participants must have pd-l1 positive tumors with cps ≥ 1 to \< 10. * participant has measurable disease, i.e., at least one measurable lesion per recist 1.1 criteria (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation) * participant has an eastern cooperative oncology group (ecog) performance status of 0 or 1 * participant has life expectancy ≥ 12 weeks from the start of study treatment key exclusion criteria: * participant has received prior treatment with immunotherapy in the metastatic setting, or anti-t cell immunoreceptor with ig and itim domains (tigit) therapy in any setting * history of severe hypersensitivity to any of the study drugs (i.e. monoclonal antibodies, gemcitabine, carboplatin, nab-paclitaxel, paclitaxel) or its excipients or to drugs of similar chemical classes * participant with inflammatory breast cancer at screening * participant has central nervous system (cns) involvement which was not previously treated and/or was newly detected at screening. previously treated cns involvement must fulfill the following criteria to be eligible for the trial: 1. completed prior therapy (including radiation and/or surgery) for cns metastases ≥ 28 days prior to the start of the study and 2. cns tumor is clinically stable at the time of screening, and 3. participant is not receiving steroids and/or enzyme inducing anti-epileptic medications for brain metastases * participant has an active autoimmune diseases or history of autoimmune diseases that may relapse * participant has not recovered from all toxicities related to prior anticancer therapies to national cancer institute (nci) ctcae version 5.0 grade ≤1. exception to this criterion: participants with any grade of alopecia are allowed to enter the study other inclusion/exclusion criteria may apply

Keywords: tnbc triple negative breast cancer pd-l1 ociperlimab tislelizumab wcd118 (bgb-a1217) vdt482 (bgb-a317) pembrolizumab carboplatin gemcitabine paclitaxel nab-paclitaxel tigit combination immunotherapy