PRODIGE 113 (FFCD 2314) - REWENEC 01 STUDY Randomized Trial of FOLFIRI + Zimberelimab + Domvanalimab vs FOLFIRI With a Hybrid Synthetic Control Arm in Second Line Treatment of Neuroendocrine Carcinoma of Gastro-enteropancreatic or Unknown Origin. Phase II Comparative Randomized Study - Multicentric

Background Neuroendocrine carcinomas (NECs) of gastro-entero-pancreatic (GEP) or unknown (UK) origin are rare and highly aggressive diseases. The recommended first-line (L1) treatment is platinum-etoposide combination therapy, which has a progression-free survival (PFS) of only 4-9 months and a median overall survival (OS) of approximately 12 months. All patients experience relapse, often rapidly after this first line of chemotherapy. The standard second-line (L2) chemotherapies recommended by ESMO, ENETS, and NCCN, FOLFIRI and FOLFOX, have modest efficacy with a PFS of 3 months and a median OS of 6 months. The BEVANEC study (PHRCK 2014, NCT02820857) reported no benefit of FOLFIRI + bevacizumab compared to FOLFIRI in a randomized phase II study that enrolled 150 patients in 26 centers over a period of 5 years in France.
To date, the most promising efficacy data for this highly aggressive cancer come from clinical trials of immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 checkpoint. For example, in France, the non-comparative phase II NIPINEC trial (NCT03591731) randomized patients to receive nivolumab +/- ipilimumab in L2/3 and achieved its primary evaluation criterion (ORR-8 weeks>10%). Other trials in Europe and worldwide have also reported efficacy data in the context of single-arm studies.
Scientific Questions and Unmet Needs:
1. New therapeutic options/perspectives are necessary for patients with GEP/UK NECs given the limited overall survival.
2. Approximately 50% of patients experienced early progression under immunotherapy in the NIPINEC trial and other trials, which may be explained by the absence of chemotherapy combined with immunotherapy and/or the existence of resistance mechanisms.
3. In the GEP/UK NEC indication, the design of these immunotherapy trials has been non-comparative single-arm studies because the realization of randomized comparative trials is considered very difficult for these very rare cancers (incidence <5/million).
Rationale for the REWENEC-01 Trial The DURIGAST PRODIGE 59 study, conducted by the FFCD, demonstrated the feasibility and safety of the FOLFIRI + double immune checkpoint inhibitor (anti-PD-1 and anti-CTLA4) combination, as well as for the combination Folfox-Domvanalimab-Zimberelimab (anti-PD-1 and anti-TIGIT). In a translational study of the immune phenotype in patients with NECs treated with the anti-PD1 pembrolizumab, an increase in TIGIT expression was observed after pembrolizumab treatment and higher TIGIT expression on T cells in the blood of patients with high Ki67 expression in their tumors. These data suggest that TIGIT is a potential complementary therapeutic target to PD-1/PD-L1 checkpoint inhibition in GEP/UK NECs. Domvanalimab has been developed as an anti-TIGIT monoclonal antibody and zimberelimab as an anti-PD-1.
Design and primary objective of the REWNEC-01 Trial The REWENEC-01 trial is a comparative phase II trial that will randomize GEP/UK NEC patients between an experimental arm FOLFIRI+Zimberelimab + Domvanalimab and a control arm FOLFIRI in L2. The FOLFIRI arm will be a "hybrid" synthetic control arm composed of patients from historical/external data from the FOLFIRI arm of BEVANEC and French retrospective studies RBNEC and CEPD, mixed with patients recruited prospectively during the trial and randomized to the control arm. The randomization ratio for patients included prospectively during the trial will be 4:1 (4 patients assigned to FOLFIRI+Zimberelimab + Domvanalimab for 1 patient assigned to FOLFIRI). The randomization algorithm will take into account "external" patients assigned progressively to the control arm to obtain a 1:1 ratio between the trial arms, with balanced distributions of stratification factors between the two arms.
With 77 patients to be included, this strategy will provide statistical power equivalent to that of a trial including 122 patients, sufficient to demonstrate an advantage in overall survival rate at 12 months from 32% to 50%.
The hypotheses related to efficacy criteria are formulated a priori, as recommended by the FDA guidance document on trials with synthetic/external control arms. The proof of concept has been reported at ESMO 2023. The primary judgment criterion will be the overall survival rate at 12 months because it is a strong and significant criterion for translating the clinical benefit of the Chemotherapy + Zimberelimab + Domvanalimab combination. The design with a hybrid synthetic control arm allows for the consideration of a randomized comparative study in a cancer as rare as neuroendocrine carcinoma.

开始日期2026-04-01

申办/合作机构

Hospices Civils de Lyon

[+1]

NCT07134556

/ Withdrawn临床2期

A Phase II Trial Evaluating the Safety and Efficacy of the Combination of Zimberelimab, Domvanalimab and Sacituzumab Govitecan as First-line Therapy for PD-L1 Positive Advanced Triple-negative Breast Cancer

The ADJUNCT is a single-arm, phase II clinical trial to evaluate the safety and efficacy of the combination of zimberelimab, domvanalimab and sacituzumab govitecan as first-line therapy for patients with PD-L1 positive advanced or metastatic triple-negative breast cancer.

开始日期2026-04-01

申办/合作机构

Medica Scientia Innovation Research SL

NCT07283848

/ Withdrawn临床2期IIT

A Single-Arm, Phase II Study of Perioperative Zimberelimab + Domvanalimab and Neoadjuvant Chemotherapy in Locally Advanced, Resectable, Gastroesophageal Adenocarcinoma

The purpose of the study is to understand whether study drugs domvanalimab and zimberelimab are safe and effective in combination with standard chemotherapy for patients with operable cancer of the esophagus, stomach, or gastroesophageal junction (where the stomach meets the esophagus).
All participants will receive the study treatment. Participants will receive chemotherapy and two immune therapies drugs (domvanalimab and zimberelimab) for up to 4 months before surgery. After surgery and at least a 4 week recovery, participants will receive domvanalimab and zimberelimab for up to 8 months. After completion of the study treatment, participants will be followed for up to 5 years per standard of care.

开始日期2026-02-01

申办/合作机构

The Massachusetts General Hospital

[+2]

100 项与 Domvanalimab 相关的临床结果

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100 项与 Domvanalimab 相关的转化医学

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100 项与 Domvanalimab 相关的专利（医药）

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项与 Domvanalimab 相关的文献（医药）

2026-05-01·LUNG CANCER

Domvanalimab combined with zimberelimab as first-line treatment in patients with PD-L1–high, advanced non-small cell lung cancer: Results from the randomized phase 2 ARC-10 study, Part 1

Article

作者: Bermingham, Candy ; Graham, Julie R ; Runglodvatana, Yotsawaj ; Naidoo, Jarushka ; Dang, Thao ; Juengsamarn, Jitlada ; Johnson, Melissa L ; Fong, Chin Heng ; How, Soon Hin ; Patel, Deepa ; Han, Sasha ; Marina, Neyssa ; Peters, Solange ; Li, Jacky Yu-Chung ; Ho, Gwo Fuang

INTRODUCTION:

TIGIT and PD-1 trigger distinct but interconnected immunosuppressive pathways. We investigated first-line domvanalimab (Fc-silent anti-TIGIT) plus zimberelimab (anti-PD-1) in PD-L1-high (≥50%), stage IIIB-IV NSCLC.

MATERIALS AND METHODS:

This phase 2, multicenter, randomized, open-label study (ARC-10, Part 1) randomized (2:2:1) patients to intravenous domvanalimab 15 mg/kg plus zimberelimab 360 mg (DZ), zimberelimab 360 mg (Z), or platinum-doublet chemotherapy every 3 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), confirmed objective response rate (ORR), and safety.

RESULTS:

Of 98 randomized patients, 95 received treatment (DZ, n = 38; Z, n = 40; chemotherapy, n = 17). As of May 17, 2024, median follow-up was 24.5 months; 22patients remained on first-line treatment (DZ, n = 11; Z, n = 10; chemotherapy, n = 1). Median (95% CI) PFS was 11.5 (4.0-26.2) months for DZ, 6.2 (2.5-12.3) months for Z, and 9.6 (2.6-16.4) months for chemotherapy. Median (95% CI) OS was not reached (13.7-not evaluable [NE]) for DZ, 24.4(7.8-NE) months for Z, and 11.9(2.7-NE) months for chemotherapy. DZ vs Z hazard ratio (95% CI) was 0.69 (0.40-1.18) for PFS and 0.64 (0.32-1.25) for OS. ORR (95% CI) was 44.7% (28.6-61.7) for DZ, 35.0% (20.6-51.7) for Z, and 35.3% (14.2-61.7) for chemotherapy. Grade ≥ 3 treatment-related adverse events (AEs) were lower for DZ (21.1%) and Z (15.0%) vs chemotherapy (47.1%). Immune-mediated AEs were similar between DZ (23.7%) and Z (20.0%). Infusion-related reactions were low (0%-7.9% across arms).

CONCLUSIONS:

Adding Fc-silent anti-TIGIT (domvanalimab) to anti-PD-1 (zimberelimab) led to encouraging efficacy and showed no new safety concerns in patients with previously untreated stage IIIB-IV NSCLC.

2026-01-01·Nature Reviews Clinical Oncology

Domvanalimab plus zimberelimab shows promise in upper-tract cancers

Article

作者: Peter Sidaway

2024-05-01·Clinical lung cancer

STAR-121: A Phase III Randomized Study of Domvanalimab and Zimberelimab in Combination With Chemotherapy Versus Pembrolizumab With Chemotherapy in Untreated Metastatic Non–Small Cell Lung Cancer With No Actionable Gene Alterations

Article

作者: Xinwei Yu ; Saad Mohammad ; Melissa Johnson ; Delvys Rodriguez-Abreu ; Jhanelle E. Gray ; Xueying Chen ; Jongseok Kim ; Trever Todd ; Martin Reck ; Joaquim Bosch-Barrera ; Myung-Ju Ahn

INTRODUCTION:

Dual inhibition with a T-cell immunoreceptor with immunoglobulin and ITIM domains plus programmed death (ligand)-1 (PD[L]-1) inhibitors, with or without chemotherapy, is an emerging therapeutic strategy in metastatic non-small cell lung cancer (mNSCLC). The STAR-121 (NCT05502237) phase III, global, randomized, open-label study will investigate first-line domvanalimab (anti-TIGIT) and zimberelimab (anti-PD-1) plus chemotherapy versus pembrolizumab plus chemotherapy in mNSCLC with no actionable gene alterations.

PARTICIPANTS AND METHODS:

Approximately 720 participants (≥18 years old) with untreated mNSCLC and no EGFR and ALK mutations will be randomized into 3 groups (A, B, or C) in a 4:4:1 ratio and stratified by baseline PD-L1 expression (tumor cells <50% vs. ≥50%), histology (squamous vs. nonsquamous), and geographic region (East Asia vs. non-East Asia). Group A will receive domvanalimab 1200 mg plus zimberelimab 360 mg plus platinum-doublet chemotherapy (PT), group B will receive pembrolizumab 200 mg plus PT, and group C will receive zimberelimab 360 mg plus PT, every 3 weeks. Treatment will be administered until disease progression or intolerable toxicity. Dual primary endpoints are progression-free survival (by blinded independent central review [BICR]) and overall survival for group A versus B. Key secondary endpoints comprise overall response rate (by BICR), safety, and quality of life. Exploratory endpoints include efficacy and safety between groups A and C, pharmacokinetics, patient-reported outcomes, and biomarkers.

CONCLUSION:

Enrollment in the STAR-121 study commenced on October 12, 2022, and is currently ongoing with completion planned by September 2024. The study completion is expected by December 2027.

259

项与 Domvanalimab 相关的新闻（医药）

2026-06-18

·ioncology

2026 ESMO GI重磅口头摘要抢先看，多瘤种诊疗新数据全面来袭

点击蓝字关注我们编者按 2026年欧洲肿瘤内科学会胃肠道肿瘤大会（ESMO GI 2026）将于7月1~4日在德国慕尼黑线下召开，并同步开启线上虚拟会议通道，汇聚全球胃肠肿瘤领域顶尖专家、临床研究者与医务工作者，聚焦胃肠肿瘤预防、诊断、综合治疗全链条的前沿进展。本届大会设置多学科病例研讨、临床争议辩论、重磅研究口头汇报等丰富学术环节，内容覆盖早期筛查、生物标志物导向精准治疗、系统治疗创新、患者生活质量管理等多个核心方向，是洞悉全球胃肠肿瘤诊疗发展趋势、交流临床实战经验的顶级学术平台。本次我们整理大会优选口头报告（Proffered Paper）与快速口头报告（Rapid oral session）核心摘要，聚焦肝癌、结直肠癌、胰腺癌、胆道肿瘤、胃食管肿瘤等主流瘤种，带大家提前解锁多项重磅临床研究成果，一睹全球胃肠肿瘤领域的最新突破。一、创新专题快速口头报告专场（7月4日08:30~10:00丨13a会议室）本场由Lorenza Rimassa、Andres Cervantes、Manuel Salto-Tellez担任主席，聚焦靶向新药、联合方案、生物标志物检测等创新方向，多项Ⅱ期、Ⅲ期及探索性研究集中亮相，覆盖胰腺癌、结直肠癌、胃食管肿瘤、胆管癌等多个瘤种。摘要号：LBA4 英文标题：TRIPP-FFX: Results of an open-label, multi-centre, randomized study of TaRgeted Intratumoural Placement of Phosphorous-32 microparticles in addition to FOLFIRINOX versus FOLFIRINOX alone in patients with unresectable locally advanced pancreatic cancer (uLAPC)中文标题：TRIPP-FFX研究：局部晚期不可切除胰腺癌患者采用磷-32微粒瘤内靶向给药联合FOLFIRINOX方案对比单用FOLFIRINOX方案的一项开放标签、多中心随机研究结果讲者：Michele Milella (Verona, Italy) 摘要号：6RO 英文标题：Calderasib (MK-1084) for KRAS G12C-mutated (mut) advanced colorectal cancer (CRC): Results from KANDLELIT-001中文标题：Calderasib（MK-1084）治疗KRAS G12C突变型晚期结直肠癌：KANDLELIT-001研究结果讲者：Rafal Dziadziuszko (Gdansk, Poland) 摘要号：495RO 英文标题：HERIZON-GEA-01: Exploratory analysis of response characteristics and PFS2 in advanced or metastatic gastroesophageal adenocarcinoma (mGEA)中文标题：HERIZON-GEA-01研究：晚期/转移性胃食管腺癌疗效特征与PFS2的探索性分析讲者：Filippo Pietrantonio (Milan, Italy) 摘要号：343RO 英文标题：Fanregratinib in fibroblast growth factor receptor 2 (FGFR2)- fusions/rearrangements intrahepatic cholangiocarcinoma (ICC): Pivotal part of a phase II trial中文标题：Fanregratinib治疗成纤维细胞生长因子受体2（FGFR2）融合/重排型肝内胆管癌：一项Ⅱ期关键性研究结果讲者：Jianming Xu (Beijing, China) 摘要号：344RO 英文标题：A phase I study of futibatinib in combination with zimberelimab and chemotherapy in first-line unresectable advanced or metastatic biliary tract cancer中文标题：Futibatinib联合Zimberelimab及化疗一线治疗不可切除晚期/转移性胆道肿瘤的Ⅰ期临床研究讲者：Kazuyoshi Ohkawa (Osaka, Japan) 摘要号：345RO 英文标题：Precemtabart tocentecan (Precem-TcT) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): Results from the Phase Ib/II PROCEADE-PanTumor PDAC substudy中文标题：Precemtabart Tocentecan治疗转移性胰腺导管腺癌：Ⅰb/Ⅱ期PROCEADE泛肿瘤研究胰腺腺癌亚组结果讲者：Zev A. 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Risumlund (Copenhagen, Denmark) 三、大会优选口头报告专场（7月2日14:00~15:30丨14会议室）本场由Eric Van Cutsem、Teresa Macarulla担任主席，核心聚焦肝细胞癌与胰腺癌两大难治性瘤种，多项Ⅲ期重磅研究公布总生存期、安全性、有效性数据，为介入联合系统治疗、靶向联合化疗方案的临床应用提供高级别证据。摘要号：LBA2 英文标题：Tumour response analyses by RECIST v1.1 and mRECIST in the Phase 3 EMERALD-3 study of tremelimumab plus durvalumab with or without lenvatinib plus transarterial chemoembolisation (TACE) in embolisation-eligible hepatocellular carcinoma (eeHCC)中文标题：Ⅲ期EMERALD-3研究：曲美木单抗联合度伐利尤单抗±仑伐替尼联合经动脉化疗栓塞（TACE）治疗适合栓塞的肝细胞癌，基于RECIST v1.1与mRECIST标准的肿瘤疗效分析讲者：Joseph P. Erinjeri (New York, United States of America) 摘要号：183O 英文标题：Overall survival (OS) in EMERALD-1: a Phase 3 study of durvalumab (D) + bevacizumab (B) and transarterial chemoembolisation (TACE) in participants (pts) with unresectable embolisation-eligible hepatocellular carcinoma (eeHCC)中文标题：Ⅲ期EMERALD-1研究：度伐利尤单抗联合贝伐珠单抗+经动脉化疗栓塞治疗不可切除且适合栓塞的肝细胞癌患者的总生存期结果讲者：Bruno Sangro (Pamplona – Madrid, Spain) 摘要号：340O 英文标题：Safety and efficacy of zoldonrasib (RMC-9805) plus chemotherapy in patients (Pts) with 1L RAS G12D metastatic pancreatic adenocarcinoma (mPDAC)中文标题：Zoldonrasib（RMC-9805）联合化疗一线治疗RAS G12D突变转移性胰腺导管腺癌的安全性与有效性讲者：Brian M. Wolpin (Boston, United States of America) 摘要号：341O 英文标题：Safety and efficacy of zoldonrasib (RMC-9805) plus daraxonrasib (RMC-6236) in patients with 2L+ KRAS G12D metastatic pancreatic adenocarcinoma (mPDAC)中文标题：Zoldonrasib（RMC-9805）联合Daraxonrasib（RMC-6236）二线及以上治疗KRAS G12D突变转移性胰腺导管腺癌的安全性与有效性讲者：Nilofer S. Azad (Baltimore, United States of America) 摘要号：342O 英文标题：Zolbetuximab plus gemcitabine and nab-paclitaxel (GN) in patients (pts) with claudin 18 isoform 2 (CLDN18.2)+ metastatic pancreatic adenocarcinoma (mPAC): Phase II GLEAM study中文标题：Zolbetuximab联合吉西他滨+白蛋白结合型紫杉醇治疗CLDN18.2阳性转移性胰腺腺癌：Ⅱ期GLEAM研究结果讲者：Wungki Park (New York, United States of America) 四、大会优选口头报告专场（7月3日16:30~18:00丨14会议室）本场由Michel P. Ducreux、Jeeyun Lee担任主席，围绕结直肠癌术后辅助治疗、KRAS突变结直肠癌二线治疗、胃食管腺癌一线方案、患者生活质量等方向展开，同时探索ctDNA在结直肠癌肝转移术后的指导价值，兼顾疗效评估、治疗策略优化与人文关怀。摘要号：8O 英文标题：ctDNA status and adjuvant chemotherapy after resection of colorectal liver metastases: an overall survival analysis of the GALAXY study中文标题：结直肠癌肝转移切除术后ctDNA状态与辅助化疗的价值：GALAXY研究总生存期分析讲者：Kozo Kataoka (Nishinomiya, Japan) 摘要号：LBA1 英文标题：Second-line adagrasib plus cetuximab vs chemotherapy in patients with KRASG12C-mutated metastatic colorectal cancer: results from the KRYSTAL-10 trial中文标题：Adagrasib联合西妥昔单抗对比化疗二线治疗KRAS G12C突变转移性结直肠癌：KRYSTAL-10研究结果讲者：Josep Tabernero (Barcelona, Spain) 摘要号：1O 英文标题：ATOMIC (A021502/AIO-KRK-0317): Does duration of adjuvant chemotherapy (chemo) or immunotherapy matter?中文标题：ATOMIC研究（A021502/AIO-KRK-0317）：辅助化疗与辅助免疫治疗的疗程长短是否影响疗效？讲者：Anke Reinacher-Schick (Bochum, Germany)特邀点评专家：Per Pfeiffer（丹麦欧登塞）问答与讨论：17:10-17:20 摘要号：493O 英文标题：STAR-221: A phase 3 study of first-line (1L) domvanalimab (D), zimberelimab (Z), and chemotherapy (chemo) vs nivolumab (N) + chemo in advanced HER2-negative gastric, gastroesophageal junction, or esophageal adenocarcinoma (GC/GEJC/EAC)中文标题：Ⅲ期研究STAR-221研究：Domvanalimab联合Zimberelimab+化疗对比纳武利尤单抗+化疗一线治疗HER2阴性晚期胃、胃食管结合部及食管腺癌讲者：Sun Young Rha (Seoul, Republic of Korea) 摘要号：494O 英文标题：Health-related quality of life (HRQoL) with zanidatamab (zani) + chemotherapy (CT) ± tislelizumab (TIS) for first-line (1L) HER2-positive (HER2+) advanced/metastatic gastroesophageal adenocarcinoma (mGEA): Results from HERIZON-GEA-01中文标题：HERIZON-GEA-01研究：Zanidatamab联合化疗±替雷利珠单抗一线治疗HER2阳性晚期/转移性胃食管腺癌的健康相关生活质量分析讲者：Kohei Shitara (Kashiwa, Japan) 作为全球胃肠肿瘤领域的标杆学术会议，2026 ESMO GI汇聚了全球前沿临床研究成果，本次公示的口头摘要覆盖精准靶向、免疫联合、介入治疗、局部消融、术后辅助、全程管理、生活质量等全维度内容，既有真实世界数据印证经典方案价值，也有新型药物、创新联合疗法、检测技术的突破性探索。从肝癌介入联合免疫的持续优化，到结直肠癌基于分子分型的分层治疗；从胰腺癌、胆管癌小众靶点新药突围，再到胃食管肿瘤免疫双抗、抗体偶联药物的临床验证，一系列研究或将重塑临床诊疗格局。后续我们也将持续跟进本届大会现场解读、专家点评及研究深度分析，第一时间传递全球胃肠肿瘤诊疗新动向，敬请持续关注！（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。

2026-06-11

·医药速览

被“困”住的吉利德，由科伦博泰华丽开路

PREFACE 前言 TROP2 ADC赛道再次迎来“同一靶点，不同命运”的分化大戏。一边是吉利德与默沙东联手推进的Trodelvy + Keytruda（K药）在一线肺癌III期试验EVOKE-03中止，另一边则是科伦博泰的Sac-TMT（芦康沙妥珠单抗）联合K药在OptiTROP-Lung05中交出几乎“碾压式”的无进展生存期（PFS）成绩单，疾病进展或死亡风险降低约65%。与此同时，第一三共与阿斯利康的Dato-DXd仍在一线肺癌谨慎推进，尚未完全揭晓终局。图源：吉利德官网对比更鲜明的在于，吉利德以约210亿美元总价收购Immunomedics，将Trodelvy纳入麾下；Dato-DXd则是继DS-8201后，阿斯利康以60亿美元总包从第一三共引进的ADC；而默沙东仅以4700万美元预付款及14亿美元总价，就从科伦博泰手中买下了Sac-TMT。如今，估值截然不同的三款产品分别迈入了失败、突破与观望的三种境地，TROP2 ADC赛道也在多靶点、多payload的竞争中，滑向了未知。 01 吉利德，困在Trodelvy之中 Trodelvy可以说是一场“高价收购+高期待落空”的典型案例。 2020年，吉利德以210亿美元收购Immunomedics，成功拿下当时头顶“全球首款TROP2 ADC”光环的Trodelvy，并成为吉利德在肿瘤领域“弯道超车”的关键一跃。收购初期，Trodelvy确实凭借ASCENT研究中的颠覆性疗效，确立了其在三阴性乳腺癌（TNBC）后线治疗中的地位，并顺利拓展至HR+/HER2-转移性乳腺癌和晚期尿路上皮癌。但对于210亿美元的估值而言，仅靠乳腺癌的盘子显然对不起吉利德的付出，Trodelvy终归要“进军”规模最大的肺癌市场，可Trodelvy在肺癌领域的探索，可谓充满了跌宕。 2023年的II期数据显示，Trodelvy与K药联用一线治疗转移性非小细胞肺癌（NSCLC）的结果喜人，PD-L1高表达患者的客观缓解率（ORR）达69%，疾病控制率（DCR）达86%。吉利德自然也雄心勃勃地推进了单药及联合疗法在肺癌领域的III期试验。可惜，2024年，Trodelvy作为单药挑战多西他赛用于二线非鳞状NSCLC的III期EVOKE-01研究宣告失败，未能达到总生存期（OS）的主要终点；如今，Trodelvy联合K药一线治疗PD-L1高表达转移性NSCLC患者的EVOKE-03研究，因PFS改善未达统计学意义，被建议提前终止研究。此外，Trodelvy在HR+/HER2-乳腺癌一线治疗、转移性尿路上皮癌后线治疗及转移性胃食管腺癌后线治疗中，都曾遭遇失败。 2025年，Trodelvy全年销售额近14亿美元，同比增长6%，从上市以来的增速来看，Trodelvy要想回本，可谓遥遥无期。 Trodelvy在NSCLC中只剩一项II期临床仍在推进，主要探索Trodelvy与Domvanalimab（抗TIGIT单抗）+Zimberelimab（PD-1单抗）的联用方案。尽管吉利德反复强调，此次挫败不会影响Trodelvy在TNBC以及高危辅助治疗（ASCENT-05）等其他正在进行的临床研究，且吉利德也在积极寻找下一代ADC接棒产品，比如通过50亿美元收购Tubulis，获得其下一代ADC技术平台及靶向NAPI2B的Tub-040。但在TROP2 ADC这个赛道上，Trodelvy正在承受分子设计代差所带来的根本劣势。 02 中国资产正在打破“高疗效-低估值”的错配对比来看，Trodelvy采用SN-38（伊立替康活性代谢物）作为payload，DAR约7.6。但SN-38的毒性窗口并不宽。而Sac-TMT与Dato-DXd均采用拓扑异构酶I抑制剂（DXd类或类似结构）。而在linker选择上，Trodelvy采用的是较为传统且相对不稳定的可水解连接子，科伦博泰的Sac-TMT则采用了稳定性更高、对pH值敏感的可裂解连接子。 ASCO上公布的数据显示，Sac-TMT联合K药组的≥3级不良事件虽有55.3%，但有效避开了Trodelvy的腹泻问题和Dato-DXd的整体间质性肺病（ILD）隐患（≥3级仅2.9%），且未出现因毒性导致的治疗终止。第一三共的Dato-DXd则采用了高度稳定的四肽连接子，搭载大名鼎鼎的DXd毒素，但为了追求安全性，将DAR值降到了极低的4。这种设计虽然大幅降低了全身系统性毒性，但其在肺癌临床中的疗效也受到了莫大的限制：如TROPION-Lung01研究中，mPFS从3.7个月提升至4.4个月，OS的HR仅为0.94。图源网络临床设计方面，吉利德的EVOKE-03研究严格限定在PD-L1 TPS≥50%的高表达NSCLC人群，这是一个对K药单药高度敏感的群体，叠加Trodelvy带来的获益空间本就有限。而科伦博泰的OptiTROP-Lung05研究全面覆盖了PD-L1阳性（包括中低表达和高表达）的患者群体，联合治疗组PFS尚未达到，对照组5.7个月，总的HR达0.35，低表达亚组中HR值低至0.28，高表达亚组中也跑出了惊艳的结果（HR 0.47）。 Dato-DXd的肺癌开发策略则包括与PD-1/PD-L1、化疗及其他药物组合，试图从非鳞NSCLC、驱动基因阴性患者等人群中找到最优切口。但Dato-DXd面对的主要是第一三共ADC产品共有的毒性问题，如ILD风险。目前Sac-TMT的适应症拓展得最广，默沙东正在推进多达17项全球III期研究，覆盖乳腺癌、肺癌、妇科肿瘤及胃肠/泌尿系统肿瘤等。Dato-DXd在肺癌领域还有8项III期临床正在展开，而Trodelvy的适应症探索集中在乳腺癌和尿路上皮癌两大确定性更高的领域。另一方面，从前文提到三款ADC产品的交易金额也可以看出，过去中国资产遭遇过许多这种“高疗效-低估值”的错配，这也是国内药企目前拓宽BD窗口的核心驱动力。国产分子用国际顶尖的数据一步步证明了自身研发实力，但在国际定价权与资本支持的溢价上，我们依然处于等待被全面重新锚定的前夜。 03 “ADC现在的开发趋势是找新payload、多payload、多靶点组合。”一位资深行业BD人员在谈及ADC未来演进时指出。此前在bioSeedin柏思荟主办的BIOS大会上，业内高管也在围绕“下一代ADC选择策略”的话题讨论中指出：国内ADC创新已经从单抗平台向双抗/三抗ADC、双毒素ADC、免疫刺激抗体偶联物（ISAC）等多元方向跃迁。这一趋势在TROP2靶点上也体现得淋漓尽致。在双靶点ADC方向上，中国药企可谓进度飞快：康宁杰瑞自研的JSKN016，作为全球首个进入III期临床的HER3×TROP2双靶点ADC，正针对TNBC、NSCLC等13项适应症全速铺开；康方生物的AK146D1将TROP2与Nectin-4这两个已在尿路上皮癌中得到验证的靶点叠加，利用双抗平台期望超越现有的单靶ADC疗效；信达生物的IBI3022则锁定了TROP2×B7-H4，旨在通过B7-H4在妇科肿瘤中的高表达和空间互补性，曲线突围。图源：智慧芽新药数据库在载荷机制的创新上，安斯泰来的ASP-2998则代表了ISAC的最新方向，其通过将TROP2抗体同时偶联TOP1抑制剂和STING激动剂，试图在一款分子上实现“直接化疗杀伤+激活固有免疫”的双重打击；康弘生物的KH815则通过其自研的双载荷平台，联合搭载TOP1抑制剂与转录阻断剂（RNA聚合酶II抑制剂），切断肿瘤细胞的耐药通路。图源：同上 TROP2早已成为ADC领域最拥挤的靶点之一，而随着化疗、免疫治疗、靶向药和ADC不断交叉组合，一款ADC药物真正要面对的是“应该用在谁身上、排在哪一线、能不能延长OS、毒性是否值得”这样更切实具体的问题。这也是为什么当前的投资人和MNC面对层出不穷的新分子设计时，也在采用一种更加审慎、务实的评估框架，优先关注能解决明确临床痛点（如ADC耐药后进展、实体瘤异质性）并具备扎实临床获益证据（PFS/ORR提升、安全性可控）的项目。科伦博泰能够脱颖而出，正是在这两点上做到了吉利德达不到的程度。康宁杰瑞、康方等企业则在接棒科伦博泰，将TROP2 ADC引入新一程竞争。推文用于传递知识，如因版权等有疑问，请于本文刊发30日内联系医药速览。原创内容未经授权，禁止转载至其他平台。 ©2021 医药速览保留所有权利往期链接 “小小疫苗”养成记 | 医药公司管线盘点人人学懂免疫学| 人人学懂免疫学（语音版）综述文章解读 | 文献略读 | 医学科普|医药前沿笔记 PROTAC技术| 抗体药物| 抗体药物偶联-ADC 核酸疫苗 | CAR技术| 化学生物学温馨提示医药速览公众号目前已经有近12个交流群（好学，有趣且奔波于医药圈人才聚集于此）。进群请扫描上方二维码，备注“姓名/昵称-企业/高校-具体研究领域/专业”，此群仅为科研交流群，非诚勿扰。简单操作即可星标⭐️医药速览，第一时间收到我们的推送 ①点击标题下方“医药速览” ②至右上角“...” ③点击“设为星标

2026-06-11

·生物技术小编

又一项III期失败，Trodelvy未能击败K药

近日，默沙东与吉利德宣布终止双方合作开展的III期临床试验KEYNOTE-D46/EVOKE-03。根据吉利德在新闻稿所称，这一决定是基于外部数据监查委员会（eDMC）建议。这是Trodelvy在非小细胞肺癌领域遭受的又一次打击，在该试验中，Keytruda+Trodelvy未能超越Keytruda单药，试验宣告失败。目前，两家公司尚未披露该试验的具体数据。 NSCLC一线/后线治疗失败 KEYNOTE-D46/EVOKE-03是一项全球多中心、开放标签、随机、阳性对照III期临床试验，主要评估与Keytruda相比，Keytruda联合Trodelvy作为转移性非小细胞肺癌（NSCLC）患者一线治疗的疗效和安全性。试验共计入组了约620名患者，这些患者按1:1比例被随机分配至Keytruda+Trodelvy、Keytruda单药的治疗。试验的主要终点是由盲法独立中心审查（BICR）的无进展生存期（PFS）和总生存期（OS）。次要终点包括客观缓解率（ORR）、缓解持续时间（DOR）、患者报告结局（PROs）。试验结果显示：在主要终点方面，观察到了PFS数值有改善，但与Keytruda单药相比未能达到统计学显著差异。而至于OS，则被eDMC认为在最终分析时能达到统计学显著性的可能性不大。安全性方面，Keytruda联合Trodelvy的安全性与两款药物已知的安全性一致，未发现新的安全性信号。这是第二项Trodelvy在NSCLC领域宣告失败的临床试验。之前，在NSCLC后线治疗中已宣告失败。2024年1月，Trodelvy在既往接受过治疗的转移性非小细胞肺癌（NSCLC）III期临床EVOKE-01未达到总生存期（OS）的主要终点，相比对照组（多西他赛），Trodelvy对OS的改善未达到统计学差异性（11.1 vs 9.8），而中位PFS也只是略有改善（4.1 vs 3.9）。该试验现已被吉利德终止开发。整体而言，随着EVOKE-01、EVOKE-03临床试验的失败，吉利德对Trodelvy在NSCLC领域的开发进行了大幅收缩，Trodelvy在NSCLC一线/后线治疗基本退出。目前，Trodelvy在NSCLC中就只剩一项II临床VELOCITY-Lung在推进，这个试验主要探索Trodelvy与domvanalimab（抗TIGIT单抗）+zimberelimab（PD-1单抗）的联用，旨在作为新诊断可切除NSCLC围手术期治疗方案。 Trodelvy光环褪去？作为第一个获批的TROP-2 ADC，Trodelvy最大的优势就是领先。在吉利德接手后，Trodelvy快速拿下了多个适应症。并且，在吉利德最初设定的临床开发计划中，意在将款药物打造成公司肿瘤投资组合的基石药物。但是随着在多个适应症的失利，因为FIC所带来的光环看起来也已经逐渐暗淡了。除了NSCLC之外，Trodelvy在一个已经获批的适应症——尿路上皮癌上也惨遭挫败。2024年5月，Trodelvy在该适应症中的验证性Ⅲ期临床TROPiCS-04宣告失败，错过OS的主要终点。这个适应症也在当年的10月被吉利德从美国市场直接自愿撤回了。目前，小细胞肺癌（SCLC）是Trodelvy在肺癌最具希望的方向，现在，Trodelvy在既往治疗过的ES-SCLC中进行III期注册试验。而在Trodelvy上经历多次失利后，吉利德也再次启动了其收购战略，对ADC加大布局。今年4月，吉利德宣布以50亿美元总价收购德国ADC新锐Tubulis，这也是2020年210亿美元收购Immunomedics后，吉利德在ADC领域的最大的一笔收购交易。参考出处: https://www.gilead.com/news/news-details/2026/merck-and-gilead-provide-update-on-phase-3-keynote-d46-evoke-03-study

100 项与 Domvanalimab 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
食管腺癌	临床3期	美国	吉利德（上海）医药科技有限公司	2022-11-21
食管腺癌	临床3期	日本	吉利德（上海）医药科技有限公司	2022-11-21
食管腺癌	临床3期	阿根廷	吉利德（上海）医药科技有限公司	2022-11-21
食管腺癌	临床3期	澳大利亚	吉利德（上海）医药科技有限公司	2022-11-21
食管腺癌	临床3期	比利时	吉利德（上海）医药科技有限公司	2022-11-21
食管腺癌	临床3期	巴西	吉利德（上海）医药科技有限公司	2022-11-21
食管腺癌	临床3期	加拿大	吉利德（上海）医药科技有限公司	2022-11-21
食管腺癌	临床3期	智利	吉利德（上海）医药科技有限公司	2022-11-21
食管腺癌	临床3期	法国	吉利德（上海）医药科技有限公司	2022-11-21
食管腺癌	临床3期	格鲁吉亚	吉利德（上海）医药科技有限公司	2022-11-21

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05329766 (EDGE-Gastric, Pubmed \| Nat Med)	临床2期	食管癌 \| 晚期胃癌 \| 晚期胃食管交界处腺癌一线 HER2-negative	41	Domvanalimab+Zimberelimab+FOLFOX	蓋繭鏇窪網繭觸獵觸蓋(鹽網築鹹廠壓窪淵選糧) = 襯鹽糧艱糧餘衊網憲積鏇廠廠願夢製衊築繭餘 (選願製獵蓋願觸鹹鬱衊, 44.5 ~ 71.6) 更多	积极	2025-10-18
				Domvanalimab+Zimberelimab+FOLFOX (PD-L1 positive)	蓋繭鏇窪網繭觸獵觸蓋(鹽網築鹹廠壓窪淵選糧) = 憲願襯範鹹壓襯壓壓製鏇廠廠願夢製衊築繭餘 (選願製獵蓋願觸鹹鬱衊, 45.1 ~ 77.1) 更多
NCT05329766 (EDGE-Gastric, ESMO2025)	临床2期	进展期胃腺癌 \| 食管腺癌 \| 晚期胃食管交界处腺癌一线 HER-2-negative	41	Domvanalimab (dom) + Zimberelimab (zim) + FOLFOX (PD-L1 Positive (TAP ≥1%))	蓋築鹹築襯簾窪廠範鹹(獵蓋網艱鏇鬱窪糧鑰夢) = 壓廠窪餘獵鑰糧築製顧願齋簾願窪簾鹽蓋觸觸 (窪繭築鑰選淵鬱選觸顧, 45 ~ 77) 更多	积极	2025-10-17
				Domvanalimab (dom) + Zimberelimab (zim) + FOLFOX (PD-L1 High (TAP ≥5%))	蓋築鹹築襯簾窪廠範鹹(獵蓋網艱鏇鬱窪糧鑰夢) = 鑰選繭艱遞餘網餘獵壓願齋簾願窪簾鹽蓋觸觸 (窪繭築鑰選淵鬱選觸顧, 45 ~ 87) 更多
NCT05329766 (EDGE-Gastric, Company_Website) 人工标引	临床2期	食管腺癌 \| 局部晚期胃食管交界处腺癌 \| 局部晚期不可切除的胃腺癌	41	Domvanalimab + Zimberelimab + FOLFOX	餘夢膚簾積糧獵遞製糧(鏇壓構鹹選餘範構網膚) = 顧製遞鏇繭鬱艱繭鹹廠築願選獵艱繭積簾積壓 (鹹鑰壓遞構齋淵網簾鹽, 45 ~ 72) 更多	积极	2025-10-12
				Domvanalimab + Zimberelimab + FOLFOX (PD‐L1 Positive (TAP ≥ 1%))	餘夢膚簾積糧獵遞製糧(鏇壓構鹹選餘範構網膚) = 鏇築壓糧夢製夢衊製繭築願選獵艱繭積簾積壓 (鹹鑰壓遞構齋淵網簾鹽, 45 ~ 77) 更多
NCT06790706 (IMMUNORARE5, ASCO2025)	临床2期	甲状腺未分化癌 BRAFV600 mutation \| TIGIT expression	24	DOMVANALIMAB + ZIMBERELIMAB combination	鑰糧網廠鏇窪餘鹹壓蓋(醖鬱遞選膚顧製窪艱夢) = 膚艱構築窪齋積鹹齋鏇壓鑰鹹醖醖膚餘遞鬱範 (醖衊壓壓齋積積顧製衊 )	积极	2025-05-30
NCT04736173 (ARC-10, BusinessWire) 人工标引	临床1期	PD-L1阳性非小细胞肺癌 PD-L1 High Expression	98	Domvanalimab plus Zimberelimab	壓願蓋壓醖選簾壓醖衊(鏇繭觸鹹廠鬱壓衊製選) = 壓餘壓網網網鹽獵糧艱蓋築鏇築蓋膚鹹糧簾廠 (醖窪廠獵鏇襯製淵網鏇, 13.7 ~ NE) 更多	积极	2024-11-05
				Zimberelimab	壓願蓋壓醖選簾壓醖衊(鏇繭觸鹹廠鬱壓衊製選) = 願繭艱壓膚蓋襯糧選淵蓋築鏇築蓋膚鹹糧簾廠 (醖窪廠獵鏇襯製淵網鏇, 7.8 ~ NE) 更多
603 (SITC2024)	临床2期	肝细胞癌	29	Domvanalimab + Zimberelimab	蓋鏇網艱顧鹽範壓衊夢(醖廠觸選壓網餘構選簾) = Treatment-related adverse events (TRAE) defined as any adverse event that was at least possibly attributed to domvanalimab plus zimberelimab occurred in 16 patients (55.2%) and SAEs attributed to study treatment occurred in 2 patients (6.9%). TRAEs that were grade 3 or greater occurred in 3 patients (10.3%) 憲顧壓選構齋襯願糧糧 (遞蓋衊醖襯襯鏇繭鏇衊 )	积极	2024-11-05
NCT05724563 (2024 SITC)	临床2期	肝细胞癌二线 \| 三线	29	Domvanalimab+赛帕利单抗	製齋簾積網鬱願窪蓋積(遞獵鏇積獵壓積構糧鑰) = 糧繭艱鑰鹹糧構蓋齋構艱網製獵鹹範鏇範網獵 (窪範獵簾網鹹夢壓顧顧 ) 更多	积极	2024-11-05
NCT05329766 (EDGE-Gastric, BusinessWire) 人工标引	临床2期	胃肠道肿瘤一线 PD-L1	41	domvanalimab+Zimberelimab+ Chemotherapy	壓夢鬱獵蓋選憲醖齋壓(鬱製選範壓鏇願鬱選顧) = 餘餘齋淵製鑰窪醖製醖憲廠廠鏇構觸衊廠獵壓 (願鬱獵願獵齋衊醖鏇壓, 9.8 ~ 13.8) 更多	积极	2024-06-01
				domvanalimab+Zimberelimab+ Chemotherapy (PD-L1-high)	壓夢鬱獵蓋選憲醖齋壓(鬱製選範壓鏇願鬱選顧) = 鑰壓襯糧齋簾願鏇鹽糧憲廠廠鏇構觸衊廠獵壓 (願鬱獵願獵齋衊醖鏇壓, 11.3 ~ NE) 更多
NCT05329766 (EDGE-Gastric, Corporate Publications) 人工标引	临床2期	食管腺癌 \| 局部晚期不可切除的胃腺癌 \| 转移性胃食管结合部腺癌一线	41	Domvanalimab+zimberelimab+chemotherapy	願廠餘範醖醖鬱襯網衊(餘範繭觸積蓋製簾積鏇) = 築廠獵糧繭夢壓範築膚積窪齋鹹遞願餘衊製顧 (廠廠鹽憲蓋淵獵製積醖, 42 ~ 74) 更多	积极	2023-11-06
				Domvanalimab+zimberelimab+chemotherapy (PD-L1-high* (TAP ≥5%))	願廠餘範醖醖鬱襯網衊(餘範繭觸積蓋製簾積鏇) = 積構鏇窪窪衊壓壓鏇鹽積窪齋鹹遞願餘衊製顧 (廠廠鹽憲蓋淵獵製積醖, 52 ~ 96) 更多
NCT04262856 (ARC-7, Corporate Publications) 人工标引	临床2期	非小细胞肺癌一线	150	zimberelimab	餘醖鏇憲夢糧蓋鏇膚觸(範鹽蓋繭餘艱襯觸繭醖) = 築餘淵顧顧醖醖觸鏇廠網衊獵膚憲醖網顧衊鏇 (艱觸糧範積膚齋壓繭窪, 17.9 ~ 44.6) 更多	积极	2023-06-03
				domvanalimab + zimberelimab	餘醖鏇憲夢糧蓋鏇膚觸(範鹽蓋繭餘艱襯觸繭醖) = 夢糧夢積繭顧衊構襯遞網衊獵膚憲醖網顧衊鏇 (艱觸糧範積膚齋壓繭窪, 26.4 ~ 54.8) 更多