PDF(Pubmed)
Abstract：
UNASSIGNED: Squamous carcinoma of the anal canal (SCAC) is a human papillomavirus (HPV)-driven cancer with poor prognosis in locally advanced or recurrent settings. Carboplatin-paclitaxel is the preferred first-line regimen for unresectable locally advanced or metastatic SCAC, with the reported median progression-free survival (PFS) and overall survival (OS) of 8.1 and 20.0 months, respectively. Immune checkpoint blockade (ICB) demonstrates improved survival in HPV-driven cervical and head and neck cancers. Retifanlimab (INCMGA00012) is an investigational humanized, hinge-stabilized, immunoglobulin G4κ monoclonal antibody targeting programmed cell death-1 (PD-1), with characteristics common to the ICB class. In POD1UM-202, retifanlimab showed substantial clinical activity and an expected safety profile in patients with advanced SCAC who progressed on platinum-based chemotherapy. Based on these encouraging results, POD1UM-303/InterAACT 2 (NCT04472429), a phase III, double-blind, randomized, multiregional study, investigates the addition of retifanlimab to the standard of care (SOC) carboplatin-paclitaxel in patients with inoperable locally recurrent or metastatic SCAC not previously treated with systemic chemotherapy.
UNASSIGNED: Patients ≥18 years with inoperable locally recurrent or metastatic SCAC, measurable disease per RECIST v1.1, and no prior systemic chemotherapy or PD-(L)1-directed therapy will be enrolled and stratified by PD-L1 expression, region, and extent of disease. Patients with well-controlled human immunodeficiency virus infection are eligible. Planned enrollment is approximately 300 patients worldwide, with a 1:1 randomization to retifanlimab or placebo. Patients will receive up to six induction cycles (24 weeks) of carboplatin (area-under-the-curve 5 on day 1) and paclitaxel (80 mg/m2 on days 1, 8, and 15) every 28 days per SOC. Concurrently, retifanlimab 500 mg or placebo will be administered intravenously in a blinded fashion on day 1 of each 28-day cycle for up to 13 cycles (1 year) in the absence of unacceptable toxicity, disease progression, withdrawal of consent, loss to follow-up, or premature discontinuation. Crossover to open-label retifanlimab will be allowed for patients assigned to placebo upon verification of progression by blinded independent central radiographic review (BICR). The primary study endpoint is PFS per RECIST v1.1 by BICR. Secondary endpoints are OS, objective response rate, duration of response, disease control rate, safety, and retifanlimab pharmacokinetics. The study is currently recruiting.
UNASSIGNED: https://clinicaltrials.gov/ct2/show/NCT04472429; https://clinicaltrialsregister.eu/ctr-search/search?query=2020-000826-24.
UNASSIGNED: Patients ≥18 years with inoperable locally recurrent or metastatic SCAC, measurable disease per RECIST v1.1, and no prior systemic chemotherapy or PD-(L)1-directed therapy will be enrolled and stratified by PD-L1 expression, region, and extent of disease. Patients with well-controlled human immunodeficiency virus infection are eligible. Planned enrollment is approximately 300 patients worldwide, with a 1:1 randomization to retifanlimab or placebo. Patients will receive up to six induction cycles (24 weeks) of carboplatin (area-under-the-curve 5 on day 1) and paclitaxel (80 mg/m2 on days 1, 8, and 15) every 28 days per SOC. Concurrently, retifanlimab 500 mg or placebo will be administered intravenously in a blinded fashion on day 1 of each 28-day cycle for up to 13 cycles (1 year) in the absence of unacceptable toxicity, disease progression, withdrawal of consent, loss to follow-up, or premature discontinuation. Crossover to open-label retifanlimab will be allowed for patients assigned to placebo upon verification of progression by blinded independent central radiographic review (BICR). The primary study endpoint is PFS per RECIST v1.1 by BICR. Secondary endpoints are OS, objective response rate, duration of response, disease control rate, safety, and retifanlimab pharmacokinetics. The study is currently recruiting.
UNASSIGNED: https://clinicaltrials.gov/ct2/show/NCT04472429; https://clinicaltrialsregister.eu/ctr-search/search?query=2020-000826-24.
摘要：
未经证实：肛管鳞状细胞癌（SCAC）是一种人乳头瘤病毒（HPV）驱动的癌症，在局部晚期或复发环境中预后不良。卡铂-紫杉醇是不可切除的局部晚期或转移性SCAC的首选一线方案，报告的中位无进展生存期（PFS）和总生存期（OS）为8.1和20.0个月，分别。免疫检查点阻断（ICB）证明了HPV驱动的宫颈癌和头颈部癌症的生存率提高。Retifanlimab（INCMGA00012）是一种研究性的人性化，铰链稳定，免疫球蛋白G4κ单克隆抗体靶向程序性细胞死亡-1（PD-1），具有ICB类的共同特征。在POD1UM-202中，retifanlimab在以铂类为基础的化疗进展的晚期SCAC患者中显示出实质性的临床活性和预期的安全性。基于这些令人鼓舞的结果，POD1UM-303/InterAACT2(NCT04472429),第三阶段，双盲,随机化，多区域研究，研究了在无法手术的局部复发或转移性SCAC之前未接受过全身化疗的患者中,在卡铂-紫杉醇标准治疗(SOC)基础上添加瑞替卡利单抗的情况.
未经证实：≥18岁不能手术的局部复发或转移性SCAC患者，根据RECISTv1.1可测量的疾病，并且没有先前的全身化疗或PD-（L）1定向治疗将被纳入并通过PD-L1表达进行分层，区域,和疾病的程度。具有良好控制的人类免疫缺陷病毒感染的患者是合格的。计划招募全球约300名患者，1：1随机分为retifanlimab或安慰剂。每个SOC每28天，患者将接受多达六个诱导周期（24周）的卡铂（第1天的曲线下面积为5）和紫杉醇（第1、8和15天的80mg/m2）。同时,retifanlimab500mg或安慰剂将在每个28天周期的第1天以盲法静脉内给药，长达13个周期（1年），在没有不可接受的毒性的情况下，疾病进展,撤回同意,后续损失，或过早停药。在通过盲法独立中央影像学检查（BICR）验证进展后，将允许分配给安慰剂的患者交叉使用开放标签retifanlimab。主要研究终点是BICR根据RECISTv1.1的PFS。次要端点是OS，客观反应率，响应的持续时间，疾病控制率,安全,和retifanlimab药代动力学。该研究目前正在招募中。
UNASSIGNED:https://clinicaltrials.gov/ct2/show/NCT04472429;https://clinicaltrialsregister。eu/ctr-search/search?query=2020-000826-24.
未经证实：≥18岁不能手术的局部复发或转移性SCAC患者，根据RECISTv1.1可测量的疾病，并且没有先前的全身化疗或PD-（L）1定向治疗将被纳入并通过PD-L1表达进行分层，区域,和疾病的程度。具有良好控制的人类免疫缺陷病毒感染的患者是合格的。计划招募全球约300名患者，1：1随机分为retifanlimab或安慰剂。每个SOC每28天，患者将接受多达六个诱导周期（24周）的卡铂（第1天的曲线下面积为5）和紫杉醇（第1、8和15天的80mg/m2）。同时,retifanlimab500mg或安慰剂将在每个28天周期的第1天以盲法静脉内给药，长达13个周期（1年），在没有不可接受的毒性的情况下，疾病进展,撤回同意,后续损失，或过早停药。在通过盲法独立中央影像学检查（BICR）验证进展后，将允许分配给安慰剂的患者交叉使用开放标签retifanlimab。主要研究终点是BICR根据RECISTv1.1的PFS。次要端点是OS，客观反应率，响应的持续时间，疾病控制率,安全,和retifanlimab药代动力学。该研究目前正在招募中。
UNASSIGNED:https://clinicaltrials.gov/ct2/show/NCT04472429;https://clinicaltrialsregister。eu/ctr-search/search?query=2020-000826-24.
