Business decision, not driven by safety concerns; no new safety signals have been observed in the ociperlimab program.

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.

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

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 review 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 availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Participants will be randomized to Arms A, B and C in a double-blind manner Participants will be enrolled in Arm D in an open-label manner