JTO Clinical and Research Reports最新文献

{"title":"Caution Against Uncritical Adoption of Neoadjuvant Chemoimmunotherapy Followed by Definitive Radiotherapy in Stages II to III NSCLC: In Response to Adib et al","authors":"Steven J. Feigenberg MD, Cole Friedes MD, Jeffrey D. Bradley MD","doi":"10.1016/j.jtocrr.2026.101007","DOIUrl":"10.1016/j.jtocrr.2026.101007","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 8","pages":"Article 101007"},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148730982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Durvalumab Consolidation Treatment Following Concurrent Chemoradiotherapy in Limited-Stage SCLC: ADRIATIC China Subgroup Analysis","authors":"Lixia Ma MD,&nbsp;Qiming Wang MD,&nbsp;Jian Fang MD,&nbsp;Anhui Shi MD,&nbsp;Lin Wu MD,&nbsp;Shun Lu MD,&nbsp;Zhengfei Zhu MD,&nbsp;Yunpeng Liu MD,&nbsp;Qifeng Wang MD,&nbsp;Hao Jiang MD,&nbsp;Xiaoling Li MD,&nbsp;Mengzhao Wang MD,&nbsp;Yuan Chen MD,&nbsp;Hongda Lu MD,&nbsp;Yuzhong Duan MD,&nbsp;Rui Meng MD,&nbsp;Liyan Jiang MD,&nbsp;Lujun Zhao MD,&nbsp;Wenbin Zhu PhD,&nbsp;Yunru Chen MD,&nbsp;Suresh Senan M.B.B.S., PhD","doi":"10.1016/j.jtocrr.2026.101022","DOIUrl":"10.1016/j.jtocrr.2026.101022","url":null,"abstract":"<div><h3>Introduction</h3><div>At the first interim analysis of the phase 3 ADRIATIC trial, durvalumab consolidation significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo in patients with limited-stage SCLC (LS-SCLC) without progression after concurrent chemoradiotherapy (cCRT). We report a prespecified subgroup analysis of patients enrolled in China.</div></div><div><h3>Methods</h3><div>Patients with stage I to III LS-SCLC were randomized to durvalumab, durvalumab plus tremelimumab (arm remained blinded), or placebo for up to 24 months. The dual primary end points were OS and PFS by blinded independent central review for durvalumab versus placebo.</div></div><div><h3>Results</h3><div>Of the global population, 95 of 530 patients (17.9%) were randomized in China; 49 of 264 versus 46 of 266 received durvalumab versus placebo. For prior cCRT, 69.4% versus 69.6% of the China subgroup received cisplatin-etoposide, and 53.1% versus 69.6% had once-daily radiotherapy; post-cCRT, 55.1% versus 67.4% received prophylactic cranial irradiation. The hazard ratio for OS (durvalumab versus placebo; median follow-up 35.5 mo) was 0.71 (95% confidence interval: 0.37–1.37). Median OS was not reached in either arm (36-mo OS: 63.7% versus 55.4%). The hazard ratio for PFS (median follow-up 27.7 mo) was 0.67 (95% confidence interval: 0.39–1.14); median PFS was 22.9 versus 14.3 months (24-mo PFS: 45.8% versus 37.6%). With durvalumab versus placebo, 16.3% versus 17.4% of patients had maximum grade 3 or 4 adverse events (AEs), 42.9% versus 21.7% had serious AEs, and 10.2% versus 13.0% discontinued treatment due to AEs; 55.1% versus 63.0% had pneumonitis/radiation pneumonitis (grade 3 or 4: 4.1% versus 4.3%).</div></div><div><h3>Conclusion</h3><div>Consolidation durvalumab demonstrated a favorable benefit to risk profile in patients with LS-SCLC without progression after cCRT who were enrolled in China.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 8","pages":"Article 101022"},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Characterization of a Patient-Derived KIF5B-RET Fusion Lung Adenocarcinoma Cell Line for Subcutaneous and Central Nervous System Tumor Models in Immunodeficient Mice","authors":"Akihiro Nishiyama MD, PhD,&nbsp;Shigeki Sato PhD,&nbsp;Hiroyuki Sakaguchi PhD,&nbsp;Hiroshi Kotani PhD,&nbsp;Kaname Yamashita PhD,&nbsp;Koushiro Ohtsubo PhD,&nbsp;Shigeki Nanjo PhD,&nbsp;Seiji Yano PhD,&nbsp;Keishi Mizuguchi PhD,&nbsp;Hiroko Ikeda PhD,&nbsp;Makiko Yamaguchi MD,&nbsp;Tamotsu Ishizuka PhD,&nbsp;Satoko Baba BSc, MT,&nbsp;Kengo Takeuchi PhD,&nbsp;Shinji Takeuchi PhD","doi":"10.1016/j.jtocrr.2026.101026","DOIUrl":"10.1016/j.jtocrr.2026.101026","url":null,"abstract":"<div><h3>Introduction</h3><div>This study presents the development and characterization of a novel lung adenocarcinoma cell line with kinesin family member 5B rearranged during transfection (<em>KIF5B-RET</em>) fusion, derived from a single patient's pleural effusion.</div></div><div><h3>Methods</h3><div>A pleural effusion sample was collected from a patient with <em>RET</em> fusion-positive NSCLC. The cell line was developed from the pleural effusion, and its characteristics were investigated in vitro and in vivo. Information on lung cancer cell lines with <em>RET</em> fusions was collected through a literature review. The characteristics of the <em>RET</em> fusion-positive cell line developed were then compared with information on <em>RET</em> fusion-positive cell lines identified in the literature.</div></div><div><h3>Results</h3><div>The newly established PB302 cell line has the following three key characteristics: high sensitivity to selective <em>RET</em> inhibitors, the ability to grow in the central nervous system, and the ability to grow subcutaneously in immunodeficient mice. These features enabled the development of central nervous system disease and subcutaneous tumor models. A comparative analysis revealed that PB302 uniquely possesses these characteristics among <em>RET</em>-positive lung adenocarcinoma cell lines.</div></div><div><h3>Conclusions</h3><div>This cell line highlights several potentials as a tool for preclinical research and drug development.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 8","pages":"Article 101026"},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148637385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continued Cemiplimab Beyond Progression With Addition of Chemotherapy in Patients With Advanced NSCLC With PD-L1 Expression of 50% or Higher: 5-Year Follow-Up From EMPOWER-Lung 1","authors":"Marina Chiara Garassino MD,&nbsp;Ana Baramidze MD,&nbsp;Saadettin Kilickap MD,&nbsp;Ahmet Sezer MD,&nbsp;Mustafa Özgüroğlu MD,&nbsp;Mahmut Gümüş MD,&nbsp;Igor Bondarenko MD,&nbsp;Miranda Gogishvili MD,&nbsp;Marina Nechaeva MD,&nbsp;Michael Schenker MD,&nbsp;Irfan Cicin MD,&nbsp;Gwo Fuang Ho MD,&nbsp;Yaroslav Kulyaba MD,&nbsp;Kasimova Zyuhal MD,&nbsp;Roxana-Ioana Scheusan MD,&nbsp;Xue Jia MPH,&nbsp;Debra A.G. McIntyre MS,&nbsp;Stefanie Chua PharmD,&nbsp;Manika Kaul MD,&nbsp;Javier Perez PhD,&nbsp;Jean-François Pouliot MD, PhD","doi":"10.1016/j.jtocrr.2026.101029","DOIUrl":"10.1016/j.jtocrr.2026.101029","url":null,"abstract":"<div><h3>Introduction</h3><div>Treatment options are limited for patients with advanced NSCLC who progress on anti–programmed cell death-ligand 1 (anti–PD-L1) monotherapy. Second-line platinum-based chemotherapy provides a short progression-free survival (PFS) of approximately 3 to 4 months. The EMPOWER-Lung 1 study allowed continued cemiplimab with the addition of platinum-based chemotherapy after progression as a second-line treatment (cemiplimab beyond progression [CBP]). Here, we report long-term outcomes in this setting.</div></div><div><h3>Methods</h3><div>Patients (<em>N</em> = 712) with advanced NSCLC were randomized 1:1 to cemiplimab or histology-appropriate chemotherapy. This exploratory analysis evaluated efficacy and safety in the CBP setting in 73 patients (of 357 in the cemiplimab arm) who had at least one scan after progression on cemiplimab and received at least one dose of chemotherapy plus cemiplimab. Responses were assessed by an independent review committee against a new baseline, defined as the last scan before the initial dose of chemotherapy.</div></div><div><h3>Results</h3><div>In the CBP setting, the objective response rate was 27.4%, the median duration of response was 11.5 months (95% confidence interval: 6.0–19.3), and median PFS was 6.4 months (95% confidence interval: 6.1–9.1). Median overall survival from the time of randomization was 27.4 months (including 15.1 mo after the addition of chemotherapy). CBP treatment benefit was observed irrespective of histology, PD-L1 levels, or response to initial first-line cemiplimab monotherapy. Grade 3 or higher treatment-emergent adverse events occurred in 35.6% of patients, and immune-mediated adverse events occurred in 2.7% of patients.</div></div><div><h3>Conclusions</h3><div>This exploratory analysis revealed the clinical benefit of continuing cemiplimab after progression with the addition of chemotherapy, without new safety signals.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 8","pages":"Article 101029"},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Activity of RET TKI Plus Chemotherapy After Progression on a RET TKI in a RET Fusion–Positive NSCLC Real-World Cohort: A Brief Report","authors":"Alvaro Guimaraes Paula MD,&nbsp;Ximeng Liu PhD,&nbsp;Amirali Karimi MD,&nbsp;Kyle Concannon MD,&nbsp;Simon Heeke PhD,&nbsp;Yasir Y. Elamin MD,&nbsp;Kaiwen Wang PharmD,&nbsp;Jenny V. Pozadzides MD,&nbsp;Natalie Vokes MD,&nbsp;Janet Tu MD,&nbsp;Anne Tsao MD, MBA, FACHE,&nbsp;Marcelo V. Negrao MD,&nbsp;Jianjun Zhang MD, PhD,&nbsp;Eric K. Singhi MD,&nbsp;Bingnan Zhang MD, MBA,&nbsp;Waree Rinsurongkawong PhD,&nbsp;Isadora Guimaraes Martins MD,&nbsp;Hai T. Tran PharmD,&nbsp;Don L. Gibbons MD, PhD,&nbsp;Monique B. Nilsson PhD,&nbsp;John V. Heymach MD, PhD","doi":"10.1016/j.jtocrr.2026.101036","DOIUrl":"10.1016/j.jtocrr.2026.101036","url":null,"abstract":"<div><h3>Introduction</h3><div><em>RET</em> fusion–driven NSCLC accounts for 2% of advanced lung adenocarcinomas, and selective RET tyrosine kinase inhibitors (RETis) are the current first-line standard-of-care treatment. However, acquired resistance to RETi can arise, and improved therapies for RETi-resistant tumors are needed.</div></div><div><h3>Methods</h3><div>This real-world retrospective cohort evaluated the outcomes of the combinations of chemotherapy with RETi (chemo/RETi) and chemotherapy with immunotherapy (chemo/IO) in patients with NSCLC who experienced progression while receiving RETi. For both groups, we assessed the overall response rate, using the Response Evaluation Criteria in Solid Tumors version 1.1; estimated progression-free survival (PFS) and overall survival using the Kaplan-Meier method; described the genomic features potentially related to RETi resistance; and analyzed safety data using the Common Terminology Criteria for Adverse Events version 5.0.</div></div><div><h3>Results</h3><div>Overall, 12 patients were included. The median PFS was 7.8 months for patients receiving chemo/RETi (<em>n</em> = 8) versus 3.5 months for patients receiving chemo/IO (<em>n</em> = 4); hazard ratio for progression or death was 0.24 (95% confidence interval: 0.07–0.83; <em>p</em> = 0.0063). The overall response rate was 38% in the chemo/RETi group and 25% in the chemo/IO group; one metabolic complete response was observed in the chemo/RETi group. Overall survival did not differ significantly between groups. Although chemo/RETi demonstrated improved outcomes, it was associated with more grade 3 treatment-related adverse events, including anemia, febrile neutropenia, and thrombocytopenia, compared with chemo/IO.</div></div><div><h3>Conclusions</h3><div>Our data support the potential efficacy of chemo/RETi after progression on RETi, with significantly better PFS than chemo/IO, albeit with higher rates of hematologic toxicities.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 8","pages":"Article 101036"},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Expression Clustering of Lung Adenocarcinoma Tumors as a Prognosis Tool to Infer Progression-Free Survival","authors":"Sébastien Renaut PhD,&nbsp;Victoria Saavedra Armero MSc,&nbsp;Dominique K. Boudreau MSc,&nbsp;Nathalie Gaudreault BSc,&nbsp;Hanie Abolfathi MSc,&nbsp;Michael Maranda-Robitaille MD, MSc,&nbsp;Fabien C. Lamaze PhD,&nbsp;Sabrina Biardel MSc,&nbsp;Andréanne Gagné MD, PhD,&nbsp;Patrice Desmeules MD, MSc,&nbsp;Philippe Joubert MD, PhD,&nbsp;Yohan Bossé PhD","doi":"10.1016/j.jtocrr.2026.101008","DOIUrl":"10.1016/j.jtocrr.2026.101008","url":null,"abstract":"<div><h3>Introduction</h3><div>Lung cancer is the leading cause of cancer-related death. Studies have reported distinct tumor type based on gene expression signatures and attempted to use this information to predict survival, with limited replicability due to tumor heterogeneity, technical artefacts, and cohort size.</div></div><div><h3>Methods</h3><div>RNA expression profiling was performed on 515 early stage resected lung adenocarcinomas from a single institution. We then used this data set to explore the potential of gene expression to stratify patients into distinct classes predictive of survival using unsupervised clustering and Cox proportional hazards model.</div></div><div><h3>Results</h3><div>Several clinicopathologic variables, including smoking history, tumor grade, and stage, were predictive of survival. Gene expression clustering analysis supports two distinct groups of tumors as the optimal solution. Despite weak clustering of tumors based on gene expression, clusters were predictive of survival, independent of clinicopathologic variables. We also tested gene expression signatures from the literature, which were again predictive of survival, but not more than pathologic staging. Nevertheless, when restricted to early stage tumors, gene expression clustering had better predictive power than pathologic staging.</div></div><div><h3>Conclusion</h3><div>We revealed that gene expression is naturally highly variable in tumors and that the optimal number of clusters is closer to two, instead of three as often reported. We argue that although pathologic stage remains an important predictive variable, gene expression-based biomarkers can serve as a useful prognostic tool for early stage lung adenocarcinomas.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 8","pages":"Article 101008"},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148637266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence in Scientific Writing – Our Editorial Position","authors":"Emily Stone MBBS, MMed, FRACP,&nbsp;Alex A. Adjei MD, PhD, FACP","doi":"10.1016/j.jtocrr.2026.101035","DOIUrl":"10.1016/j.jtocrr.2026.101035","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 8","pages":"Article 101035"},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148730983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarker Testing Among Patients With Nonsquamous NSCLC Across Three Time Periods and Three Testing Platforms—A Brief Report","authors":"Zhen (Jason) Fan MD,&nbsp;Roxana Tudor MSc,&nbsp;Michael Cabanero MD,&nbsp;Lisa W. Le MSc,&nbsp;Mary Rabey MD,&nbsp;Jennifer H. Law MSc,&nbsp;Tracey Stockley PhD,&nbsp;Shelley Kuang MD,&nbsp;Nicholas Meti MD,&nbsp;Andreas Fung MD,&nbsp;Kirstin Perdrizet MD,&nbsp;Kaitlin Chen MHSc,&nbsp;Janice J.N. Li MSc,&nbsp;Noor Ghumman MD,&nbsp;Laura Ranich BSc,&nbsp;Cuihong Wei PhD,&nbsp;Peter Sabatini PhD,&nbsp;Prodipto Pal MD,&nbsp;Ying-Han R. Hsu MD,&nbsp;Hyang Mi Ko MD,&nbsp;Natasha B. Leighl MD","doi":"10.1016/j.jtocrr.2026.101012","DOIUrl":"10.1016/j.jtocrr.2026.101012","url":null,"abstract":"<div><div>Biomarker testing in stage III/IV nonsquamous NSCLC is critical in treatment decision-making. This ambispective review included 1028 patients across three time periods to evaluate the clinical impact of evolving genomic testing platforms. Cohort 1 (C1: 2015–2017) had reflex EGFR/ALK testing. Cohort 2 (C2: 2017–2020) used limited next-generation sequencing (NGS; 15 genes), ALK, and ROS1 testing. Cohort 3 (C3: 2020–2022) used comprehensive NGS (161 genes). Larger NGS panels identified more actionable genomic alterations, but increased biopsy-to-result turnaround times and fewer patients had complete molecular results at first medical oncology consultation leading to delays in treatment initiation.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 8","pages":"Article 101012"},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Outcomes for Patients who Received Both Trastuzumab Deruxtecan (T-DXd) and Trastuzumab Emtansine (T-DM1) for HER2-Mutant non-Small Cell Lung Cancer","authors":"Daniel Reinhorn MD,&nbsp;Jonathan Kuten MD, MHA,&nbsp;Isabel Preeshagul DO, MBS,&nbsp;Juliana Eng MD,&nbsp;Kenneth Ng MD,&nbsp;Alexander Drilon MD,&nbsp;Jamie Chaft MD,&nbsp;Fernando C. Santini MD,&nbsp;Mark M. Awad MD, PhD","doi":"10.1016/j.jtocrr.2026.101024","DOIUrl":"10.1016/j.jtocrr.2026.101024","url":null,"abstract":"<div><h3>Background</h3><div>Trastuzumab deruxtecan (T-DXd) and trastuzumab emtansine (T-DM1) are HER2-targeting antibody-drug conjugates (ADCs) with activity in <em>HER2</em>-mutant non-small cell lung cancer (NSCLC). Whether patients benefit from sequential HER2-directed ADCs therapy remains unknown.</div></div><div><h3>Methods</h3><div>We conducted a single-center retrospective study of patients with <em>HER2</em>-mutant NSCLC who received both T-DXd and T-DM1 in either order. Clinical characteristics, confirmed overall response rate, real-world progression-free survival (rwPFS), and overall survival (OS) were evaluated. All time-to-event endpoints were calculated from the start of the second ADC.</div></div><div><h3>Results</h3><div>Twenty-five patients were identified: 17 received T-DM1 post-T-DXd and 8 received T-DXd post-T-DM1. The median age for the entire cohort was 67 years; 56% were female. Most patients (21/25, 84%) harbored <em>HER2</em> kinase-domain mutations, while 3 had extracellular and 1 had transmembrane domain alterations. The median number of prior systemic therapies before the second ADC was three. Seventeen patients (68%) received the two ADCs in direct sequence without other intervening therapies. In the T-DM1 post-T-DXd cohort, the median rwPFS was 3.3 months (95% CI, 1.9–5.6) and the median OS was 9.2 months (95% CI, 4.9–NR). No confirmed responses were observed; however, two patients (12%) achieved unconfirmed partial responses, and one had prolonged stable disease for 13.9 months. In the T-DXd post-T-DM1 cohort, the median rwPFS was 5.2 months (95% CI, 4.1–NR) and the median OS was 25.0 months (95% CI, 8.2–NR); three patients (37.5%) achieved confirmed partial responses.</div></div><div><h3>Conclusions</h3><div>T-DXd retains clinical activity after prior T-DM1 use, whereas T-DM1 has limited efficacy after prior T-DXd in <em>HER2</em>-mutant NSCLC. Understanding the mechanisms of response and resistance to ADCs will hopefully help to inform treatment strategies using sequential ADCs in lung cancer and other malignancies.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 7","pages":"Article 101024"},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13325295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein Overexpressing, Nonsquamous, EGFR Wild-type Advanced NSCLC: Updated Analysis of the LUMINOSITY Trial","authors":"Nicolas Girard MD,&nbsp;Jonathan Goldman MD,&nbsp;Shun Lu MD, PhD,&nbsp;Jair Bar MD, PhD,&nbsp;Hidehito Horinouchi MD, PhD,&nbsp;Nathalie Daaboul MD,&nbsp;Chunling Liu MD,&nbsp;Irfan Çiçin MD,&nbsp;Nuran Katgi MD,&nbsp;Alona Zer MD,&nbsp;Tudor Ciuleanu MD, PhD,&nbsp;Niels Reinmuth MD,&nbsp;David Planchard MD, PhD,&nbsp;Se-Hoon Lee MD, PhD,&nbsp;Aaron S. Mansfield MD,&nbsp;Mor Moskovitz MD,&nbsp;Shobhit Baijal MBBS BSc (Hons), MRCP,&nbsp;Christina Baik MD, MPH,&nbsp;John S. Hrom MD, FACP,&nbsp;Rebecca S. Heist MD, MPH,&nbsp;D. Ross Camidge MD, PhD","doi":"10.1016/j.jtocrr.2026.100988","DOIUrl":"10.1016/j.jtocrr.2026.100988","url":null,"abstract":"<div><h3>Introduction</h3><div>Telisotuzumab vedotin (Teliso-V) is a c-Met–directed antibody–drug conjugate comprising the monoclonal antibody telisotuzumab and the monomethyl auristatin E payload. Primary analysis of the phase 2 LUMINOSITY trial (NCT03539536) revealed Teliso-V monotherapy 1.9 mg/kg elicited durable responses and had generally manageable safety in patients with locally advanced or metastatic c-Met protein overexpressing, <em>EGFR</em> wild-type, nonsquamous NSCLC. We present updated outcomes with approximately 6 months longer follow-up and explore the impact of previous therapies.</div></div><div><h3>Methods</h3><div>Patients (≥18 y; had previous therapy including ≤1 chemotherapy) received 1.9 mg/kg Teliso-V every 2 weeks. c-Met protein overexpression (clinical trial assay for MET [SP44] [Roche]) was defined as greater than or equal to 25% tumor cells with 3+ staining intensity (c-Met high: ≥50% 3+; c-Met intermediate: 25 to &lt;50% 3+). Primary end point was the overall response rate by independent central review per the Response Evaluation Criteria in Solid Tumors version 1.1.</div></div><div><h3>Results</h3><div>As of February 21, 2024, 172 patients received at least one dose of Teliso-V; 168 patients (c-Met high, n = 84; c-Met intermediate, n = 84) were evaluable for efficacy. The overall response rate was 29.2% (95% confidence interval [CI]: 22.4–36.7; c-Met high, 34.5% [24.5–45.7]; c-Met intermediate, 23.8% [15.2–34.3]). Median duration of response was 7.2 months (95% CI: 5.5–11.0; c-Met high, 7.2 [95% CI: 4.2–12.0]; c-Met intermediate, 7.2 [95% CI: 4.7–11.5]). Previous therapy (platinum, immune checkpoint inhibitors, or both) did not impact efficacy outcomes. The most common treatment-related adverse event was peripheral sensory neuropathy (any-grade: 31%; grade ≥3: 7%).</div></div><div><h3>Conclusions</h3><div>Teliso-V monotherapy 1.9 mg/kg elicited durable responses, irrespective of the type of previous therapy received, and maintained a manageable safety profile in patients with c-Met protein overexpressing <em>EGFR</em> wild-type, nonsquamous NSCLC.</div></div><div><h3>ClinicalTrials.gov ID number</h3><div>NCT03539536.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 7","pages":"Article 100988"},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13293683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}