AdvanTIG-301：一项ociperlimab联合替雷利珠单抗及同步放化疗治疗不可切除III期非小细胞肺癌的III期研究
AdvanTIG-301: a phase III study of ociperlimab plus tislelizumab and concurrent chemoradiotherapy in stage III unresectable non-small cell lung cancer.
作者
作者单位
- Department of Radiation Oncology, Affiliated Cancer Hospital of Shandong First Medical University, Jinan, Shandong, China.
- Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan.
- Department of Radiation Oncology, Gustave Roussy, Villejuif, France.
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California, USA.
- Virginia Cancer Specialists, US Oncology Research, NEXT Oncology Virginia, Fairfax, Virginia, USA.
- State Key Laboratory of Molecular Oncology, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
- Departments of Radiation Oncology, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
- Baptist Health Medical Group, Lexington, Kentucky, USA.
- Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
- Medical Oncology Department, University Hospital Fundacion Jimenez Diaz, Instituto de investigación sanitaria FJD (IIS-FJD), Madrid, Spain.
- Department of Radiation Oncology, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing, China.
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
- Statistics Department, BeOne Medicines Ltd, Beijing, China.
- Clinical Development, BeOne Medicines Ltd, Shanghai, China.
- Department of Radiation Oncology, Affiliated Cancer Hospital of Shandong First Medical University, Jinan, Shandong, China sdyujinming@126.com solange.peters@chuv.ch.
- Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland sdyujinming@126.com solange.peters@chuv.ch.
摘要
中文
不可切除的III期非小细胞肺癌（NSCLC）患者对新疗法存在未满足的需求，以改善生存。这项III期试验研究了同步ociperlimab和替雷利珠单抗联合同步放化疗（cCRT）在初治III期NSCLC患者中的安全性和有效性。在这项III期、多中心、随机、多臂、开放标签试验中，不可切除的III期NSCLC患者接受同步ociperlimab联合替雷利珠单抗和cCRT，随后ociperlimab联合替雷利珠单抗（A组）、替雷利珠单抗和cCRT，随后替雷利珠单抗（B组），或cCRT，随后度伐利尤单抗（C组）（NCT04866017）。目标是比较A组与C组、B组与C组、A组与B组的无进展生存期（PFS）、总生存期（OS）、客观缓解率（ORR）、缓解持续时间、疾病控制率、临床获益率、至死亡或远处转移时间（TTDM）以及安全性和耐受性。在早期试验终止前，63名患者被随机分配至A组（N=22）、B组（N=19）和C组（N=22）。在A、B、C组中，分别有95.5%（21/22）、84.2%（16/19）和95.5%（21/22）为当前或既往吸烟者，68.2%（15/22）、73.7%（14/19）和68.2%（15/22）的肿瘤细胞PD-L1表达≥1%。A组中位PFS（95% CI）未达到（NR）（6.3-不可估计（NE）），B组为15.0个月（7.4至NE），C组为10.4个月（5.7至NE）。任何组的中位OS和TTDM均未达到。A组ORR（95% CI）为68.2%（45.1%-86.1%），B组为68.4%（43.4%-87.4%），C组为59.1%（36.4%-79.3%）；所有缓解均为部分缓解。所有患者均发生治疗出现的不良事件（TEAE）；在A、B、C组中，肺炎发生率分别为18.2%（4/22）、5.6%（1/18）和9.1%（2/22），间质性肺病发生率分别为13.6%（3/22）、11.1%（2/18）和0%，其中大多数事件为1/2级。≥3级治疗相关TEAE在A、B、C组患者中分别占68.2%（15/22）、66.7%（12/18）和68.2%（15/22）。与cCRT后度伐利尤单抗相比，在cCRT基础上加用替雷利珠单抗（联用或不联用ociperlimab）后继续替雷利珠单抗（联用或不联用ociperlimab）有改善疗效的趋势；然而，疗效数据仅用于描述性目的。未发现意外或新的安全性信号。
English
Patients with unresectable stage III non-small cell lung cancer (NSCLC) have an unmet need for new therapies that improve survival. This phase III trial investigated the safety and efficacy of concurrent ociperlimab and tislelizumab plus concurrent chemoradiotherapy (cCRT) in treatment-naïve patients with stage III NSCLC. In this phase III, multicenter, randomized, multiarm, open-label trial, patients with unresectable stage III NSCLC received concurrent ociperlimab plus tislelizumab and cCRT, followed by ociperlimab plus tislelizumab (arm A), tislelizumab and cCRT, followed by tislelizumab (arm B), or cCRT, followed by durvalumab (arm C) (NCT04866017). Objectives were to compare progression-free survival (PFS), overall survival (OS), objective response rate (ORR), duration of response, disease control rate, clinical benefit rate, time to death or distant metastasis (TTDM), and safety and tolerability for arms A versus C, B versus C, and A versus B. 63 patients were randomized to arms A (N=22), B (N=19), and C (N=22) prior to early trial termination. In A, B, and C, respectively, 95.5% (21/22), 84.2% (16/19), and 95.5% (21/22) were current or former smokers, and 68.2% (15/22), 73.7% (14/19), and 68.2% (15/22) had PD-L1 expression in tumor cells of ≥1%. Median PFS (95% CI) was not reached (NR) (6.3-not estimable (NE)) in A, 15.0 months (7.4 to NE) in B, and 10.4 months (5.7 to NE) in C. Median OS and TTDM were NR in any arm. ORR (95% CI) was 68.2% (45.1%-86.1%) in A, 68.4% (43.4%-87.4%) in B, and 59.1% (36.4%-79.3%) in C; all responses were partial responses. Treatment-emergent adverse events (TEAEs) occurred in all patients; in arms A, B, and C, respectively, pneumonitis occurred in 18.2% (4/22), 5.6% (1/18), and 9.1% (2/22) of patients, and interstitial lung disease occurred in 13.6% (3/22), 11.1% (2/18), and 0% of patients, of which the majority of events for each were grade 1/2. Grade ≥3 treatment-related TEAEs occurred in 68.2% (15/22), 66.7% (12/18), and 68.2% (15/22) of patients in arms A, B, and C, respectively. There was a trend toward improved efficacy when adding tislelizumab with or without ociperlimab to cCRT followed by tislelizumab with or without ociperlimab compared with cCRT followed by durvalumab; however, efficacy data were for descriptive purposes only. No unexpected or new safety signals were identified.
分类与指标
- 研究类型
- 临床研究
- 病种
- 肺癌
- JCR 分区
- Q1
- 影响因子
- 11.7
- 新锐分区
- 1区