Clinical trial NCT05809895: 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
Official title: AdvanTIG-211: A Randomized, Double-blind, Placebo-controlled, Phase II Study Evaluating the Efficacy and Safety of Ociperlimab (WCD118) Combined With Tislelizumab (VDT482) Plus Chemotherapy Versus Placebo Combined With Pembrolizumab Plus Chemotherapy as First-line Therapy for Participants With Advanced Triple Negative Breast Cancer (TNBC)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Triple Negative Breast Cancer
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-04-12
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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

Primary outcomes:
measure: Progression-free Survival (PFS) based on investigator assessment using RECIST 1.1 criteria in Arm A and B
timeFrame: From randomization to date of disease progression or death, assessed up to approximately 32 months after first randomization
Secondary outcomes:
measure: Overall Survival (OS) based on investigator assessment using RECIST 1.1 criteria in Arm A, B and C
timeFrame: From randomization to death, assessed up to approximately 32 months after first randomization
measure: Overall Response Rate (ORR) based on investigator assessment using RECIST 1.1 criteria in Arm A, B and C
timeFrame: Up to approximately 32 months after first randomization
measure: Clinical benefit rate (CBR) with confirmed response in Arm A, B and C
timeFrame: Approximately 32 months after first randomization
measure: Time to response (TTR) based on investigator assessment using RECIST 1.1 criteria in Arm A, B and C
timeFrame: From randomization to first documented response, assessed up to approximately 32 months after first randomization
measure: Duration of Response (DOR) based on investigator assessment using RECIST 1.1 criteria in Arm A, B and C
timeFrame: From first documented response to disease progression or death, assessed up to approximately 32 months after first randomization
measure: Progression-free Survival (PFS) based on investigator assessment using RECIST 1.1 criteria in Arm A, B and C
timeFrame: From randomization to date of disease progression or death, assessed up to approximately 32 months after first randomization
measure: Number of participants with dose modifications
timeFrame: Approximately 32 months after first dose
measure: Anti-drug Antibodies (ADA) prevalence at Baseline for ociperlimab
timeFrame: Baseline
measure: Anti-drug Antibodies (ADA) prevalence at Baseline for tislelizumab
timeFrame: Baseline
measure: Anti-drug Antibodies (ADA) incidence on treatment for ociperlimab
timeFrame: From Cycle 1 to Cycle 16, end of treatment and 30 day safety follow-up. Each cycle is 21 days
measure: Anti-drug Antibodies (ADA) incidence on treatment for tislelizumab
timeFrame: From Cycle 1 to Cycle 16, end of treatment and 30 day safety follow-up. Each cycle is 21 days
measure: Change from baseline in the Functional Assessment of Cancer Therapy-Breast (FACT-B) Trial Outcomes Index (TOI) score
timeFrame: Up to approximately 32 months after first dose
measure: Time to 5-point definitive deterioration in FACT-B TOI score
timeFrame: Up to approximately 32 months after first dose
measure: Serum concentrations of ociperlimab
timeFrame: Cycle (C) 1 Day (D) 1, C1D2, C1D4, C1D8, C1D15, D1 of C2, C3, C4 and C5, C5D8, D1 of C6, C8, C12 and C16, end of treatment and 30 day post-treatment. Each cycle is 21 days.
measure: Serum concentrations of tislelizumab
timeFrame: Cycle (C) 1 Day (D) 1, C1D2, C1D4, C1D8, C1D15, D1 of C2, C3, C4 and C5, C5D8, D1 of C6, C8, C12 and C16, end of treatment and 30 day post-treatment. Each cycle is 21 days.
Other outcomes:
Locations:
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: