PO.CT01.04 · 临床试验

Taletrectinib治疗酪氨酸激酶抑制剂（TKI）经治的ROS1+非小细胞肺癌（NSCLC）患者：TRUST-I和TRUST-II的更新数据

Taletrectinib in tyrosine kinase inhibitor (TKI)-pretreated patients with ROS1+ non-small cell lung cancer (NSCLC): Updated data from TRUST-I and TRUST-II

编号 CT244 展板 9 时间 4/21 02:00–05:00 区域 Section 50 主讲 Geoffrey Liu, MD

分会场 Phase II Clinical Trials

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作者与单位 Authors & Affiliations

Geoffrey Liu¹, Jorge Nieva², Lyudmila Bazhenova³, Chang-Min Choi⁴, Qitao Yu⁵, Shunichi Sugawara⁶, Noriko Yanagitani⁷, Filippo de Braud⁸, Huijie Fan⁹, Enriqueta Felip¹⁰, Emilio Bria¹¹, Maurice Pérol¹², Feiwu Ran¹³, Wei Wang¹³, Xianyu Zhang¹³, Michael Chen¹³, Caicun Zhou¹⁴

¹Princess Margaret Cancer Centre, Temerty School of Medicine, University of Toronto, Toronto, ON, Canada,²Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA,³Moores Cancer Center, University of California San Diego, San Diego, CA,⁴Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of,⁵Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China,⁶Sendai Kousei Hospital, Sendai, Japan,⁷Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan,⁸University of Milan, Milan, Italy,⁹The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China,¹⁰Vall d'Hebron University Hospital, Barcelona, Spain,¹¹Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy,¹²Léon Bérard Cancer Center, Lyon, France,¹³Nuvation Bio Inc., New York, NY,¹⁴Shanghai East Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China

摘要 Abstract

中文摘要

背景：Taletrectinib是一种新一代、具有中枢神经系统（CNS）活性的选择性ROS1 TKI，已获美国FDA批准用于治疗局部晚期/转移性ROS1+ NSCLC患者（pts）。在两项2期研究TRUST-I（NCT04395677）和TRUST-II（NCT04919811）中，taletrectinib在TKI初治和TKI经治的ROS1+ NSCLC患者中显示出强劲的疗效，包括颅内（IC）活性和对G2032R突变的疗效，以及可耐受的安全性特征（Pérol M等，J Clin Oncol 2025）。本文报告TKI经治患者约3年随访的更新数据。方法：TRUST-I和TRUST-II的研究设计此前已有报道（Pérol M等，J Clin Oncol 2025）。疗效人群包括来自TRUST-I和TRUST-II、经独立审查委员会按RECIST v1.1评估具有≥1个可测量基线病灶的患者。安全性人群包括来自1期和2期研究、接受≥1剂taletrectinib 600 mg每日一次的ROS1+ NSCLC患者。结果：截至2025年8月31日，汇总疗效分析纳入113例TKI经治患者（66例来自TRUST-I[既往crizotinib]；47例来自TRUST-II[37例既往crizotinib，10例既往entrectinib]）。中位（m）随访35.8个月（mo）时，确认ORR为55.8%（95% CI 46.1-65.1），mDOR为16.6个月（95% CI 10.7-24.9），mPFS为9.7个月（95% CI 7.6-12.0），mOS为29.8个月（95% CI 23.2-46.0）。在具有G2032R突变（8/13；ORR 61.5%[95% CI 31.6-86.1]）和CNS转移（IC-ORR 65.6%[95% CI 46.8-81.4]）的患者中均观察到缓解。按试验划分的数据见表。TKI经治患者与安全性人群（n=363）的安全性相似。结论：随着随访时间延长，taletrectinib在TKI经治患者中维持了持久缓解，包括对CNS转移和G2032R突变的活性，且安全性特征可耐受。这些数据支持taletrectinib作为既往TKI治疗后ROS1+ NSCLC患者一种有效且可耐受的治疗选择。 TKI经治患者疗效汇总。疗效全部TKI经治患者（N=113） TRUST-I（n=66） TRUST-II（n=47）中位随访，月 35.8 45.2 30.5 cORR，%（95% CI） 55.8（46.1-65.1） 51.5（38.9-64.0） 61.7（46.4-75.5）中位DOR，a 月（95% CI） 16.6（10.7-24.9） 13.2（7.7-24.8） 19.4（10.7-NR）中位PFS，月（95% CI） 9.7（7.6-12.0） 7.6（5.5-12.0） 11.8（7.7-19.6） IC疗效 b（N=32）（n=16）（n=16） IC-ORR，%（95% CI） 65.6（46.8-81.4） 75.0（47.6-92.7） 56.3（29.9-80.3） a DOR仅在缓解者中报告。b 由IRC按mRECIST v1.1在具有≥1个可测量基线脑转移的患者中评估。 c，确认；CI，置信区间；DOR，缓解持续时间；IC，颅内；IRC，独立审查委员会；mo，月；mRECIST v1.1，改良实体瘤缓解评估标准1.1版；NR，未达到；ORR，客观缓解率；PFS，无进展生存期；pts，患者；TKI，酪氨酸激酶抑制剂。

查看英文原文 English abstract

Background: Taletrectinib is a next-generation, CNS-active, selective ROS1 TKI approved by the US FDA for the treatment of patients (pts) with locally advanced/metastatic ROS1+ NSCLC. In two Phase 2 studies, TRUST-I (NCT04395677) and TRUST-II (NCT04919811), taletrectinib showed robust efficacy, including intracranial (IC) activity and efficacy against G2032R mutations, and a tolerable safety profile in TKI-naïve and TKI-pretreated pts with ROS1+ NSCLC (Pérol M, et al. J Clin Oncol 2025). Here we report updated data in TKI-pretreated pts with ~3 years of follow-up. Methods: The study designs of TRUST-I and TRUST-II have been previously reported (Pérol M, et al. J Clin Oncol 2025). The efficacy population included pts from TRUST-I and TRUST-II with ≥1 measurable baseline lesion per RECIST v1.1 by independent review committee. The safety population included pts with ROS1+ NSCLC from Phase 1 and 2 studies who received ≥1 dose of taletrectinib 600 mg once daily. Results: As of Aug 31, 2025, the pooled efficacy analysis included 113 TKI-pretreated pts (66 from TRUST-I [prior crizotinib]; 47 from TRUST-II [37 prior crizotinib, 10 prior entrectinib]). With a median (m) follow-up of 35.8 months (mo), confirmed ORR was 55.8% (95% CI 46.1-65.1), mDOR was 16.6 mo (95% CI 10.7-24.9), mPFS was 9.7 mo (95% CI 7.6-12.0), and mOS was 29.8 mo (95% CI 23.2-46.0). Responses were observed in pts with G2032R mutations (8/13; ORR 61.5% [95% CI 31.6-86.1]) and with CNS metastases (IC-ORR 65.6% [95% CI 46.8-81.4]). Data by trial are shown in the Table. Safety was similar between TKI-pretreated pts and the safety population (n=363). Conclusion: With longer follow-up, taletrectinib maintained durable responses in TKI-pretreated pts, including activity against CNS metastases and G2032R mutations, with a tolerable safety profile. These data support taletrectinib as an effective and tolerable treatment option for pts with ROS1+ NSCLC after prior TKI therapy. Efficacy summary in TKI-pretreated pts. Efficacy All TKI-pretreated pts (N=113) TRUST-I (n=66) TRUST-II (n=47) Median follow-up, mo 35.8 45.2 30.5 cORR, % (95% CI) 55.8 (46.1-65.1) 51.5 (38.9-64.0) 61.7 (46.4-75.5) Median DOR, a mo (95% CI) 16.6 (10.7-24.9) 13.2 (7.7-24.8) 19.4 (10.7-NR) Median PFS, mo (95% CI) 9.7 (7.6-12.0) 7.6 (5.5-12.0) 11.8 (7.7-19.6) IC efficacy b (N=32) (n=16) (n=16) IC-ORR, % (95% CI) 65.6 (46.8-81.4) 75.0 (47.6-92.7) 56.3 (29.9-80.3) a DOR reported in responders only. b Assessed by IRC per mRECIST v1.1 in pts with ≥1 measurable baseline brain metastasis. c, confirmed; CI, confidence interval; DOR, duration of response; IC, intracranial; IRC, independent review committee; mo, months; mRECIST v1.1, modified Response Evaluation Criteria In Solid Tumors version 1.1; NR, not reached; ORR, objective response rate; PFS, progression-free survival; pts, patients; TKI, tyrosine kinase inhibitor.

利益披露 Disclosure

G. Liu, Nuvation Bio; Amgen; AstraZeneca; Takeda; Bayer; Boehringer Ingelheim; Gilead; EMD Serono Other, Grant/contract. J. Nieva, Genentech Other, Research Grant, Invited speaker, advisory board. AstraZeneca Other, Writing engagements, advisory board. Aadi Biosciences; ANP Technologies; BioAtla; BMS; Catalym; Daiichi Sankyo; Gilead; Kalivir; Sanofi; Pfizer; Takeda; Tubulis; Urogen Other, Advisory board. Affyimmune Other Business Ownership, Other, Board of Directors. Cansera Other Business Ownership, Other, Royalties. Indee Bio Other Business Ownership. Amgen; Johnson & Johnson; Novartis Stock. Merck Other, Research Grant. L. Bazhenova, JNJ; Revolution medicine; AbbVie; Eli Lilly; BMS; Pfizer; Nuvalent; Taiho Oncology; Summit; Bayer; Boerhinger Ingleheim; Genentech; Natera; Merck; Anheart Independent Contractor. C. Choi, None.. Q. Yu, None. S. Sugawara, AbbVie; Amgen; AnHeart; AstraZeneca; Bristol Myers Squibb; Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo, Delta-Fly Pharma; GSK; IQVIA; Merck Sharp & Dohme K.K.; Nippon Boehringer Ingelheim Other, Local PI. Novocure; Parexel International; PharmaMar; PPD-SNBL; Taiho Pharmaceutical Other, Local PI. Amgen; AstraZeneca; Bristol Myers Squibb; Chugai Pharmaceutical Co., Ltd.; Daiichi-Sankyo; Eisai; Kyowa Kirin; Lilly; Merck; Merck Sharp & Dohme K.K.; Nippon Boehringer Ingelheim; Nippon Kayaku Other, Lecture fee. Novartis; Ono Pharmaceutical Co., Ltd.; Pfizer; Sysmex; Taiho Pharmaceutical Co. Ltd.; Takeda; Thermo Fisher Scientific Other, Lecture fee. N. Yanagitani, AstraZeneca; Pfizer Japan; Ono Pharmaceuticals; Chugai Pharmaceutical Co., Ltd; Bristol-Myers Squibb; Daiichi Sankyo Company Limited; Eli Lilly Other, Payment or honoraria for lectures. F. de Braud, Pierre Fabre; Mattioli 1885; MCCann Health; MSD; IQVIA; Novartis; Indene; lncyte; Taiho Pharmaceutical; Menarini; Roche Other, Consulting. Sanofi; BMS; Taiho Pharmaceutical; Incyte Other, Advisory arrangements. AnHeart Therapeutics; Apollomics; AstraZeneca; Basilea Pharmaceutica; Bayer Healthcare; Boehringer lngelheim; BMS; F. Hoffmann-La Roche; lncyte; Itanet; Janssen-Cilag; Kymab; Loxo Oncology Other, P.I.. Medlmmune; Merck KGaA; Novartis; Tesaro Other, P.I.. Nadirex; ESO; Dephaforum; Ambrosetti; Motore Sanity; Effetti; Events; Fare Comunicazione; ltanet; Nadirex; BMS; Accmed; Idea-z; Dynamicom Education; Sanofi; AstraZeneca Other, Speakers' bureau. lncyte; BMS; Novartis; Sanofi; AstraZeneca Other, Traveling expenses. H. Fan, None. E. Felip, AbbVie; Amgen; AstraZeneca; Boehringer Ingelheim; Bristol Myers Squibb; Daichii Sankyo; Genentech/Roche; GlaxoSmithKline; Iteos Therapeutics; Janssen/Johnson & Johnson; Merck Sharp & Dohme Other, Consulting fees. Pierre Fabre; Pfizer; Pharmamar; Seagen; Regeneron; Tubulis; Moderna; Ellipses Pharma Other, Consulting fees. Amgen; Daiichi Sankyo; Eli Lilly; Roche/Genentech; Gilead; Janssen/Johnson & Johnson; Medical Trends; Medscape; Merck Sharp & Dohme; Peervoice; Pfizer Other, Speaker's bureau. AstraZeneca; Johnson & Johnson; Roche; Amgen Travel. Grifols Other, Independent member of the board. E. Bria, AstraZeneca; Roche Other, Grant/Contract. AstraZeneca; Roche; MSD; Takeda; Pierre-Farbre; Pfizer; Eli-Lilly; Amgen; Celltrion Other, Advisory board. M. Pérol, AstraZeneca; Pfizer; Amgen; Bristol-Myers Squibb; Novocure; Merck Sharp & Dohme; Sanofi; Pharmamar; Janssen; Ipsen Other, Invited speaker. AstraZeneca; Bristol-Myers Squibb; Amgen Other, Expert testimony. Eli Lilly; Pfizer; Merck Sharp & Dohme; Bristol-Myers Squibb; Novartis; AstraZeneca; Takeda; Sanofi; Amgen; AbbVie; Ipsen; Esaï; Daiichi Sankyo; Janssen; Novocure; Pharmamar Other, Advisory board. Eli Lilly, Merck Sharp & Dohme; Bristol-Myers Squibb; Amgen; AstraZeneca; AbbVie; Daiichi Sankyo; AnHeart Therapeutics; Nuvation Bio; Takeda; Roche Other, Principal investigator. AnHeart Therapeutics Other, Advisory role. F. Ran, Nuvation Bio Inc Employment, Stock. W. Wang, Nuvation Bio Inc Employment. X. Zhang, Nuvation Bio Inc Employment, Stock. M. Chen, Nuvation Bio Inc Employment. C. Zhou, None.

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