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)
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Progression-free Survival (PFS) based on investigator assessment using RECIST 1.1 criteria in Arm A and B
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
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
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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≥
- •For Arm D, participants must have PD-L1 positive tumors with CPS ≥ 1 to <
- •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
排除标准
- •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:
- •Completed prior therapy (including radiation and/or surgery) for CNS metastases ≥ 28 days prior to the start of the study and
- •CNS tumor is clinically stable at the time of screening, and
- •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 ≤
- •Exception to this criterion: participants with any grade of alopecia are allowed to enter the study
- •Other inclusion/exclusion criteria may apply
研究组 & 干预措施
Arm A: ociperlimab+tislelizumab+chemotherapy (PD-L1 CPS ≥ 10)
Participants with a PD-L1 CPS ≥ 10 will receive after randomization ociperlimab + tislelizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Ociperlimab (Drug)
Arm A: ociperlimab+tislelizumab+chemotherapy (PD-L1 CPS ≥ 10)
Participants with a PD-L1 CPS ≥ 10 will receive after randomization ociperlimab + tislelizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Tislelizumab (Drug)
Arm A: ociperlimab+tislelizumab+chemotherapy (PD-L1 CPS ≥ 10)
Participants with a PD-L1 CPS ≥ 10 will receive after randomization ociperlimab + tislelizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Paclitaxel (Drug)
Arm A: ociperlimab+tislelizumab+chemotherapy (PD-L1 CPS ≥ 10)
Participants with a PD-L1 CPS ≥ 10 will receive after randomization ociperlimab + tislelizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Nab-paclitaxel (Drug)
Arm A: ociperlimab+tislelizumab+chemotherapy (PD-L1 CPS ≥ 10)
Participants with a PD-L1 CPS ≥ 10 will receive after randomization ociperlimab + tislelizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Carboplatin (Drug)
Arm A: ociperlimab+tislelizumab+chemotherapy (PD-L1 CPS ≥ 10)
Participants with a PD-L1 CPS ≥ 10 will receive after randomization ociperlimab + tislelizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Gemcitabine (Drug)
Arm B: placebo + pembrolizumab + chemotherapy (PD-L1 CPS ≥ 10)
Participants with a PD-L1 CPS ≥ 10 will receive after randomization placebo + pembrolizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Paclitaxel (Drug)
Arm B: placebo + pembrolizumab + chemotherapy (PD-L1 CPS ≥ 10)
Participants with a PD-L1 CPS ≥ 10 will receive after randomization placebo + pembrolizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Nab-paclitaxel (Drug)
Arm B: placebo + pembrolizumab + chemotherapy (PD-L1 CPS ≥ 10)
Participants with a PD-L1 CPS ≥ 10 will receive after randomization placebo + pembrolizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Carboplatin (Drug)
Arm B: placebo + pembrolizumab + chemotherapy (PD-L1 CPS ≥ 10)
Participants with a PD-L1 CPS ≥ 10 will receive after randomization placebo + pembrolizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Placebo (Drug)
Arm B: placebo + pembrolizumab + chemotherapy (PD-L1 CPS ≥ 10)
Participants with a PD-L1 CPS ≥ 10 will receive after randomization placebo + pembrolizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Pembrolizumab (Drug)
Arm B: placebo + pembrolizumab + chemotherapy (PD-L1 CPS ≥ 10)
Participants with a PD-L1 CPS ≥ 10 will receive after randomization placebo + pembrolizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Gemcitabine (Drug)
Arm C: placebo + tislelizumab + chemotherapy (PD-L1 CPS ≥ 10)
Participants with a PD-L1 CPS ≥ 10 will receive after randomization placebo + tislelizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Tislelizumab (Drug)
Arm C: placebo + tislelizumab + chemotherapy (PD-L1 CPS ≥ 10)
Participants with a PD-L1 CPS ≥ 10 will receive after randomization placebo + tislelizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Paclitaxel (Drug)
Arm C: placebo + tislelizumab + chemotherapy (PD-L1 CPS ≥ 10)
Participants with a PD-L1 CPS ≥ 10 will receive after randomization placebo + tislelizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Nab-paclitaxel (Drug)
Arm C: placebo + tislelizumab + chemotherapy (PD-L1 CPS ≥ 10)
Participants with a PD-L1 CPS ≥ 10 will receive after randomization placebo + tislelizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Carboplatin (Drug)
Arm C: placebo + tislelizumab + chemotherapy (PD-L1 CPS ≥ 10)
Participants with a PD-L1 CPS ≥ 10 will receive after randomization placebo + tislelizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Placebo (Drug)
Arm C: placebo + tislelizumab + chemotherapy (PD-L1 CPS ≥ 10)
Participants with a PD-L1 CPS ≥ 10 will receive after randomization placebo + tislelizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Gemcitabine (Drug)
Arm D: ociperlimab + tislelizumab + chemotherapy (PD-L1 CPS score ≥ 1 to < 10)
Exploratory arm: Participants with a PD-L1 CPS ≥ 1 to < 10 will receive ociperlimab + tislelizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Ociperlimab (Drug)
Arm D: ociperlimab + tislelizumab + chemotherapy (PD-L1 CPS score ≥ 1 to < 10)
Exploratory arm: Participants with a PD-L1 CPS ≥ 1 to < 10 will receive ociperlimab + tislelizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Tislelizumab (Drug)
Arm D: ociperlimab + tislelizumab + chemotherapy (PD-L1 CPS score ≥ 1 to < 10)
Exploratory arm: Participants with a PD-L1 CPS ≥ 1 to < 10 will receive ociperlimab + tislelizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Paclitaxel (Drug)
Arm D: ociperlimab + tislelizumab + chemotherapy (PD-L1 CPS score ≥ 1 to < 10)
Exploratory arm: Participants with a PD-L1 CPS ≥ 1 to < 10 will receive ociperlimab + tislelizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Nab-paclitaxel (Drug)
Arm D: ociperlimab + tislelizumab + chemotherapy (PD-L1 CPS score ≥ 1 to < 10)
Exploratory arm: Participants with a PD-L1 CPS ≥ 1 to < 10 will receive ociperlimab + tislelizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Carboplatin (Drug)
Arm D: ociperlimab + tislelizumab + chemotherapy (PD-L1 CPS score ≥ 1 to < 10)
Exploratory arm: Participants with a PD-L1 CPS ≥ 1 to < 10 will receive ociperlimab + tislelizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Progression-free Survival (PFS) based on investigator assessment using RECIST 1.1 criteria in Arm A and B
时间窗: From randomization to date of disease progression or death, assessed up to approximately 32 months after first randomization
PFS is defined as the time from the date of randomization to the date of first documented progression or death due to any cause. The comparison of PFS between Arm A and Arm B will be provided
次要结局
- Time to response (TTR) based on investigator assessment using RECIST 1.1 criteria in Arm A, B and C(From randomization to first documented response, assessed up to approximately 32 months after first randomization)
- Anti-drug Antibodies (ADA) prevalence at Baseline for tislelizumab(Baseline)
- Time to 5-point definitive deterioration in FACT-B TOI score(Up to approximately 32 months after first dose)
- Overall Response Rate (ORR) based on investigator assessment using RECIST 1.1 criteria in Arm A, B and C(Up to approximately 32 months after first randomization)
- Progression-free Survival (PFS) based on investigator assessment using RECIST 1.1 criteria in Arm A, B and C(From randomization to date of disease progression or death, assessed up to approximately 32 months after first randomization)
- Duration of Response (DOR) based on investigator assessment using RECIST 1.1 criteria in Arm A, B and C(From first documented response to disease progression or death, assessed up to approximately 32 months after first randomization)
- Number of participants with dose modifications(Approximately 32 months after first dose)
- Anti-drug Antibodies (ADA) incidence on treatment for tislelizumab(From Cycle 1 to Cycle 16, end of treatment and 30 day safety follow-up. Each cycle is 21 days)
- Change from baseline in the Functional Assessment of Cancer Therapy-Breast (FACT-B) Trial Outcomes Index (TOI) score(Up to approximately 32 months after first dose)
- Serum concentrations of tislelizumab(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.)
- Clinical benefit rate (CBR) with confirmed response in Arm A, B and C(Approximately 32 months after first randomization)
- Anti-drug Antibodies (ADA) prevalence at Baseline for ociperlimab(Baseline)
- Anti-drug Antibodies (ADA) incidence on treatment for ociperlimab(From Cycle 1 to Cycle 16, end of treatment and 30 day safety follow-up. Each cycle is 21 days)
- Serum concentrations of ociperlimab(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.)
- Overall Survival (OS) based on investigator assessment using RECIST 1.1 criteria in Arm A, B and C(From randomization to death, assessed up to approximately 32 months after first randomization)