Sym-021

点击蓝字 关注我们 编者按 备受全球肿瘤学界关注的2025年欧洲肿瘤内科学会亚洲年会（ESMO Asia）即将于12月5日~7日在新加坡拉开帷幕，近日大会官网已公布除重磅研究摘要（LBA）外的全部摘要内容。在备受瞩目的Proffered Paper session: Gastrointestinal tumours专场中，共有5项核心摘要入选，涵盖3项口头报告与2项LBA摘要。考虑到亚洲是胃肠道肿瘤的高发区域，《肿瘤瞭望消化时讯》特别提前梳理了3项口头报告的核心数据，尤其是针对亚洲患者的疗效与安全性分析，为广大临床医师及科研人员提供前沿参考。 摘要号270O ✓ 度伐利尤单抗联合FLOT方案，亚洲胃/胃食管交界处腺癌患者迎新选择 讲者：Yelena Y. Janjigian（美国纽约） 背景：胃癌在亚洲地区的发病率居高不下，显著高于全球平均水平，临床亟需更高效的围手术期治疗方案改善患者预后。此前全球Ⅲ期MATTERHORN试验（NCT04592913）已在《新英格兰医学杂志》发表重磅结果，证实围手术期度伐利尤单抗联合FLOT（5-氟尿嘧啶、亚叶酸钙、奥沙利铂和多西他赛）化疗，相较于安慰剂联合FLOT，可显著提升可切除胃/胃食管交界处（G/GEJ）腺癌患者的无事件生存期（EFS）。本次亚组分析聚焦亚洲患者，旨在验证该方案在亚洲人群中的疗效和安全性数据。 方法：该研究为全球多中心Ⅲ期随机双盲试验，纳入经组织学确认的可切除Ⅱ-Ⅳa期、未接受过治疗的G/GEJ腺癌患者，按1:1随机分配至度伐利尤单抗组（1500 mg，每4周1次）或安慰剂组，两组均联合FLOT化疗（每2周1次，共4周期，新辅助与辅助治疗各2周期），后续分别接受对应单药维持治疗10周期。本次分析重点评估亚洲亚组（日本、韩国、中国台湾）的EFS、中央评审病理完全缓解率（pCR，改良Ryan标准）及安全性指标。 结果：全球948例随机患者中，180例（19.0%）来自亚洲。值得注意的是，亚洲患者相较于全分析集（FAS）具有更具挑战性的临床特征：ECOG体能状态0级比例更高（92.8% vs. 74.2%）、T4期疾病比例显著更高（57.2% vs. 24.7%）、胃癌占比更高（87.2% vs. 67.5%）、临床淋巴结阳性比例更高（77.8% vs. 70.4%）。即便如此，度伐利尤单抗+FLOT组仍展现出更优的EFS获益，风险比（HR）=0.74（95%CI：0.44~1.22），与全球人群结果一致；24个月EFS率分别为72.1% vs. 64.2%。pCR同样与全球人群保持一致，未出现显著差异（表1）。安全性方面，两组3/4级不良事件（AE）及因AE中断治疗的发生率相当，未观察到亚洲人群特有的安全信号。 表1. 结果数据 结论：MATTERHORN试验亚洲亚组分析证实，度伐利尤单抗联合FLOT方案在亚洲可切除G/GEJ腺癌患者中，即便面对更晚期、更复杂的病情，仍能带来与全球人群一致的疗效获益，且安全性可控。这一结果为该方案在亚洲临床实践中的推广应用提供了强有力的循证医学证据，有望改变亚洲地区G/GEJ腺癌的围手术期治疗格局。 临床试验标识：NCT04592913。 摘要号271O ✓ JUPITER-06最终分析，特瑞普利单抗联合化疗改写食管鳞癌生存结局 讲者：Yanxing Chen（中国广州） 背景：食管鳞状细胞癌（ESCC）是我国高发的恶性肿瘤类型，晚期患者预后极差，一线治疗方案的优化需求迫切。JUPITER-06试验（NCT03829969）中期分析已显示，特瑞普利单抗联合紫杉醇和顺铂作为晚期或转移性ESCC一线治疗，可显著改善患者无进展生存期（PFS）和总生存期（OS）。本次公布的最终分析数据进一步验证长期生存获益，并深入探索了预测疗效的基因组生物标志物。 方法：研究共纳入514例初治晚期或转移性ESCC患者，按1:1随机分为特瑞普利单抗联合化疗组与安慰剂联合化疗组。主要研究终点为独立中心评审的PFS和OS。为挖掘生物标志物，研究者对486例患者的肿瘤组织进行全外显子测序，系统分析基因组特征与治疗获益的关联性。 结果：截至2023年2月23日，中位随访时间达14.2个月。最终分析结果显示，特瑞普利单抗组OS持续优于安慰剂组，中位OS分别为17.7个月 vs. 12.9个月（HR=0.72；95%CI：0.58~0.88；双侧P=0.002），3年OS率更是提升近10个百分点（29.7% vs. 19.9%），充分证实联合方案的长期生存获益。 生物标志物探索方面，传统的PD-L1表达和肿瘤突变负荷（TMB）与特瑞普利单抗的长期获益无显著相关性，但拷贝数变异校正的TMB（ccTMB）展现出明确的预测价值——ccTMB较高患者的3年OS率达43.6%，显著高于低ccTMB患者的24.6%。 更值得关注的是，基于基因组构建的免疫肿瘤学分类（EGIC）方案表现优异，可有效识别联合治疗的长期幸存者，特瑞普利单抗组EGIC分型优势人群的3年OS率达48.9%，而安慰剂组仅为16.8%。安全性方面，延长随访未发现新的安全信号，联合方案耐受性良好。 结论：JUPITER-06试验最终分析为特瑞普利单抗联合化疗作为晚期/转移性ESCC一线标准治疗提供了坚实证据，持续的OS获益和可控的安全性使其成为临床优选方案。同时，ccTMB和EGIC分型的发现，为ESCC免疫联合治疗的个体化筛选提供了全新方向，有望推动该领域进入精准治疗时代。 临床试验标识：NCT03829969。 摘要号272O ✓ TOURMALINE早期数据，胆道癌免疫联合治疗亚洲人群显潜力 讲者：Oh Do-Youn（韩国首尔） 背景：晚期胆道癌（aBTC）治疗长期陷入瓶颈，化疗疗效有限且安全性待优化。度伐利尤单抗联合吉西他滨为基础的化疗已在TOPAZ-1试验中证实有效，并成为我国首个获批的胆道癌免疫治疗方案。全球单臂Ⅲb期TOURMALINE研究（NCT05771480）进一步拓展该联合策略的临床应用，本次公布的中期分析聚焦亚洲患者亚组，探索其早期安全性与疗效。 方法：入组患者接受度伐利尤单抗1500 mg输注（首剂60分钟，后续30分钟），联合研究者选择的吉西他滨为基础的化疗方案（包括吉西他滨单药或联合奥沙利铂、卡铂等多种组合）。研究主要终点为6个月内治疗相关3/4级AE发生率。当全球≥60例患者随访≥6个月时进行中期分析，本次重点呈现亚洲患者的安全性数据及ORR（实体瘤疗效评价标准1.1版）。数据截止日期为2024年8月7日。 结果：中期分析共纳入121例治疗患者，其中90例来自亚洲（韩国49例、日本36例、新加坡5例），占比达74.4%，充分体现亚洲人群代表性。亚洲患者中位年龄66.5岁，接受度伐利尤单抗治疗的中位周期数为6.0周期，中位安全随访时间6.0个月。 安全性方面，6个月内治疗相关3/4级AE发生率为53.3%（95%CI：42.51~63.93），与全球TOURMALINE人群及TOPAZ-1研究结果一致。亚洲亚组中，2例死亡事件被判定与治疗无关，11例因AE中断治疗，整体耐受性符合预期（表2）。 疗效方面，亚洲患者中期ORR达26.7%（95%CI：17.9~37.0），在早期随访阶段展现出良好的抗肿瘤活性。 表2. 亚洲亚组安全性数据 结论：TOURMALINE研究亚洲亚组早期数据表明，度伐利尤单抗联合吉西他滨为基础的化疗方案在亚洲晚期胆道癌患者中安全性可控，与既往全球研究结果一致，且中期ORR展现出可观潜力。该结果进一步支持免疫联合化疗在亚洲胆道癌患者中的应用价值，为临床治疗选择提供了更多循证依据。 临床试验标识：NCT05771480。 总之 ，以上三项研究均聚焦亚洲高发胃肠道肿瘤，从胃/胃食管交界处腺癌、食管鳞癌到胆道癌，覆盖多个关键癌种，其结果不仅为现有治疗方案提供了亚洲人群的有效性验证，更在生物标志物探索等方面取得突破性进展。让我们共同期待ESMO Asia大会的正式召开，解锁更多肿瘤治疗的前沿洞见！ 摘要原文 （上下滑动可查看） 摘要号：270OEfficacy and safety of perioperative durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric/gastroesophageal junction (G/GEJ) adenocarcinoma in Asia: A subgroup analysis of the MATTERHORN trial Lecture Time：09:00 - 09:10 Speakers：Yelena Y. Janjigian (New York, US) AbstractBackground Gastric cancer (GC) is highly prevalent in Asia and better treatments are needed. MATTERHORN (NCT04592913) showed perioperative durvalumab (D) + FLOT significantly improved event-free survival (EFS) vs placebo (P) + FLOT in participants (pts) with resectable G/GEJ adenocarcinoma (Janjigian et al. NEJM 2025). Here, we report the efficacy and safety of D + FLOT vs P + FLOT for the subgroup of pts enrolled in Asia.Methods In this global, Phase 3, randomised, double-blind study, pts with histologically confirmed, resectable (Stage Ⅱ–iva), untreated G/GEJ adenocarcinoma were randomised 1:1 to D 1500 mg or P every 4 weeks (Q4W; Day 1 of each cycle) plus FLOT Q2W (Days 1 and 15 of each cycle) for 4 cycles (2 cycles each neoadjuvant/adjuvant), followed by D 1500 mg or P Q4W for 10 cycles. EFS (time from randomisation to progression, local or distant recurrence, or death), pathological complete response (pCR) by central review (Modified Ryan), and safety were assessed in pts from Asia (Japan, Republic of Korea, and Taiwan).Results Of 948 randomised pts, 180 (19.0%) were enrolled in Asia. Asian pts vs pts in the full analysis set (FAS) had higher rates of ECOG performance status of 0 (92.8% vs 74.2%), stage T4 disease (57.2% vs 24.7%), GC (87.2% vs 67.5%), and positive clinical lymph-node status (77.8% vs 70.4%). In Asian pts, EFS was improved with D + FLOT vs P + FLOT (HR, 0.74; 95% CI, 0.44–1.22), consistent with the FAS (Table); the 24-month EFS rate was higher with D + FLOT (72.1 %) vs P + FLOT (64.2%). pCR rates were consistent between Asian pts and the FAS (Table). Any AE of maximum Grade 3/4 (Table) and any AE leading to discontinuation of any study treatment were comparable between arms in Asian pts. Table: 270O *Data previously published in Janjigian et al. NEJM 2025.†SAS: D + FLOT, n=90; P + FLOT, n=88.‡SAS: D + FLOT, n=475; P + FLOT, n=469.AE, adverse event; CI, confidence interval; HR, hazard ratio; NR, not reached; OR, odds ratio; SAS, safety analysis setConclusions Consistent with global MATTERHORN results, D + FLOT improved efficacy vs P + FLOT with a manageable safety profile in Asian pts with resectable G/GEJ adenocarcinoma.Clinical trial identification NCT04592913.摘要号：271OFinal analysis and biomarker evaluation of JUPITER-06: A phase Ⅲ trial of toripalimab plus chemotherapy in advanced or metastatic esophageal squamous cell carcinoma Lecture Time：09:10 - 09:20 Speakers：Yanxing Chen (Guangzhou, CN) AbstractBackground Interim analysis of JUPITER-06 trial (NCT03829969) demonstrated significant improvement in both progression-free survival (PFS) and overall survival (OS) of toripalimab plus chemotherapy as first-line treatment for advanced or metastatic esophageal squamous cell carcinoma (ESCC). Here, we report the final outcomes and explore the potential genomic biomarkers predictive of long-term survival of JUPITER-06 trial.Methods A total of 514 previously untreated patients with advanced or metastatic ESCC were randomly assigned in a 1:1 ratio to receive either toripalimab or placebo, in combination with paclitaxel and cisplatin. The primary endpoints were PFS assessed by a blinded independent central review and OS. Whole exome sequencing was performed to characterize genomic profiles in 486 patients.Results As of February 23, 2023, the median follow-up time was 14.2 months. A significant improvement in OS was observed for the toripalimab arm over the placebo arm: 17.7 months [95% CI 14.6–20.8] vs 12.9 months [95% CI 11.6–14.1], HR 0.72 [95% CI 0.58–0.88]; two-sided P = 0.002. The 3-year OS rates were 29.7% vs 19.9%, respectively. Neither PD-L1 expression nor tumor mutation burden (TMB) correlated with long-term survival benefit in toripalimab arm. Patients in toripalimab arm with higher copy number alteration-corrected TMB (ccTMB) exhibited a significant improvement in 3-year OS rate compared to those with lower ccTMB (43.6% vs 24.6%). The established genome-based immuno-oncology classification (EGIC) scheme effectively identified long-term survivors on anti-PD-1 plus chemotherapy (3-year OS rates: 48.9% vs 16.8% for toripalimab vs placebo arm). No new safety signal was identified during the extended follow-up period.Conclusions Final analysis of the JUPITER-06 trial confirms the sustained OS benefit of toripalimab plus chemotherapy as first-line treatment in advanced/metastatic ESCC, with a manageable safety profile. ccTMB and the extended EGIC scheme show promising predictive value for long-term survival in anti-PD-1-based combination therapies.Clinical trial identification NCT03829969.摘要号：272O  TOURMALINE study of durvalumab (D) in combination with gemcitabine (G)-based chemotherapy in advanced biliary tract cancer (aBTC): early safety and efficacy results in participants (pts) from Asia Lecture Time：09:58 - 10:08 Speakers：Do-Youn Oh (Seoul, KR) AbstractBackground The ongoing global, single-arm, Phase 3B TOURMALINE study (NCT05771480) assesses the safety and efficacy of D + G-based chemotherapy as first-line treatment (tx) in aBTC. We report early safety and efficacy data within a subgroup of pts from Asia.Methods Pts receive D 1500 mg (first infusion: 60 min; subsequent infusions: 30 min) with an investigator-selected G-based chemotherapy (D + G alone or in combination with oxaliplatin [O], carboplatin [C], cisplatin [cis], tegafur-gimeracil-oteracil [S-1], cis + S-1, or cis + nab-paclitaxel [P]). The primary endpoint is incidence of Grade 3/4 adverse events (AEs) possibly related (PRAEs) to any study tx within 6 months of tx initiation. This interim analysis was performed when ≥60 pts globally had been followed for ≥6 months (data cut-off [DCO]: 7 Aug 2024). Here, safety and objective response rate (ORR; per Response Evaluation Criteria in Solid Tumors, version 1.1) were evaluated in pts from Asia.Results At this interim analysis, 121 pts received treatment, including 90 pts from Asia (Korea [n=49]; Japan [n=36]; Singapore [n=5]). Pts from Asia had a median age of 66.5 years and received a median 6.0 cycles of D; median safety follow-up was 6.0 months. Grade 3/4 PRAEs within 6 months of initiation of any study tx occurred in 53.3% (95% confidence interval [CI], 42.51–63.93) of pts from Asia (Table). Overall, 2 pts from Asia had AEs with an outcome of death that were assessed as not related to any study tx; 11 pts had AEs leading to discontinuation of any study tx. The interim ORR was 26.7% (95% CI, 17.9–37.0) for pts from Asia (n=90).  Table: 272OConclusions In pts from Asia, the safety profiles of all study tx were manageable. Safety results for pts from Asia were comparable to the global TOURMALINE population and TOPAZ-1 study. Interim ORR is promising.Clinical trial identification NCT05771480. （来源：肿瘤瞭望消化时讯） 声 明 凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

Shanghai and Hong Kong, PRC, December 2, 2025 — Antengene Corporation Limited (“Antengene”, SEHK: 6996.HK), a leading innovative, commercial-stage global biotech company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for autoimmune disease, solid tumors and hematological malignancies indications, today announced that the China National Medical Products Administration (NMPA) has approved the investigational new drug (IND) application for the Phase Ib/II CLINCH-2 study evaluating ATG-022 (CLDN18.2 antibody-drug conjugate [ADC]) in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), as well as ATG-022 in combination with pembrolizumab and chemotherapy. CLINCH-2 is a Phase Ib/II study that will be led by its principal investigator Prof. Lin Shen at Beijing Cancer Hospital, the lead trial center. The study is designed to evaluate two combination regimens in patients with CLDN18.2-positive, HER2-negative, and PD-L1-positive (CPS≥1) unresectable or metastatic gastric cancer or gastroesophageal junction adenocarcinoma (GC/GEJC): ATG-022 in combination with pembrolizumab (A+P); and ATG-022 in combination with pembrolizumab plus the CAPOX chemotherapy regimen (A+P+C). The primary objective of the study is to assess the safety and tolerability of the two combination regimens, while the secondary objectives include evaluating the regimens’ preliminary antitumor activity, assessing ATG-022’s immunogenicity, and characterizing its pharmacokinetic (PK) profile. Antengene released updated clinical data from the Phase I/II CLINCH study of ATG-022 monotherapy in patients with advanced GC/GEJC at the European Society for Medical Oncology Congress 2025 (ESMO 2025). For details of the dataset, please refer to the press release published on October 20, 2025 (https://www.antengene.com/newsinfo/449). The results demonstrated clear differentiation for ATG-022 in both safety and efficacy. In the 1.8 mg/kg dose cohort, the incidence of grade 3 or higher treatment-related adverse events was only 18.2%. Moreover, the study did not observe any ocular toxicity or interstitial lung disease, and the incidence of peripheral neuropathy reported in the study was relatively low. The efficacious doses (1.8mg/kg and 2.4mg/kg) have both demonstrated an objective response rate (ORR) of 40%. This is a strong validation of ATG-022’s potential in combination with pembrolizumab and chemotherapy in the frontline setting. In addition, antitumor activity was observed across high, medium, and low CLDN18.2 expression levels, supporting the use of IHC 1+ ≥1% as the enrollment threshold for frontline combination therapy, indicating potential applicability to a much broader patient population compared to other CLDN18.2-targeting therapies. Furthermore, in the basket cohort of other CLDN18.2+ tumor types, efficacy was observed in a gynecologic tumor subtype, providing early proof of concept for potential expansion into tumor types beyond gastric cancer. Antengene will continue to advance both the ongoing CLINCH study and the newly approved CLINCH-2 study, with plans to share updated results at upcoming medical conferences to further demonstrate the clinical potential of ATG-022. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. About ATG-022    ATG-022 is a CLDN18.2-targeted antibody-drug conjugate (ADC) with sub-nM affinity and fast internalization. Using a VC-MMAE linker-payload (DAR 4), ATG-022 has demonstrated potent activity across tumors with high, low, and ultra-low CLDN18.2 expression. ATG-022 has been granted two Orphan Drug designations (ODDs) by the U.S. Food and Drug Administration (FDA) for the treatment of gastric cancer and pancreatic cancer, and obtained Breakthrough Therapy Designation from China’s National Medical Products Administration (NMPA) for treating CLDN18.2-positive, HER-2 negative unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma (GC/GEJC) who have received at least two prior lines of therapy. About Antengene Antengene Corporation Limited (“Antengene”, SEHK: 6996.HK) is a global, R&D-driven, commercial-stage biotech company focused on developing first-in-class/best-in-class therapeutics for diseases with significant unmet medical needs. Its pipeline spans from preclinical to commercial stages and includes several in-house discovered programs, including ATG-022 (CLDN18.2 ADC), ATG-037 (oral CD73 inhibitor), ATG-101 (PD-L1 × 4-1BB bispecific antibody), ATG-031 (CD24-targeting macrophage activator), and ATG-042 (oral PRMT5-MTA inhibitor). Antengene has also developed AnTenGager™, a proprietary T cell engager 2.0 platform featuring “2+1” bivalent binding for low-expressing targets, steric hindrance masking, and proprietary CD3 sequences with fast on/off kinetics to minimize cytokine release syndrome (CRS) and enhance efficacy. These characteristics support the platform’s broad applicability across autoimmune disease, solid tumors and hematological malignancies indications. To date, Antengene has obtained 32 investigational new drug (IND) approvals in the U.S. and Asia, and submitted new drug applications (NDAs) in 11 Asia Pacific markets. Its lead commercial asset, XPOVIO® (selinexor), is approved in the Mainland of China, Taiwan China, Hong Kong China, Macau China, South Korea, Singapore, Malaysia, Thailand, Indonesia and Australia. Forward-looking statements   The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development. For a further discussion of these and other factors that could cause future results to differ materially from any forward-looking statement, please see the other risks and uncertainties described in the Company’s Annual Report for the year ended December 31, 2024, and the documents subsequently submitted to the Hong Kong Stock Exchange.