Clinical Cancer Research最新文献

筛选
英文 中文
HBV-Specific TCR-T Cell Therapy Combining mRNA Electroporation and Lentiviral Transduction: Treatment Regime for Recurrent HBV-Related HCC Post-Liver Transplantation. 结合mRNA电穿孔和慢病毒转导的hbv特异性TCR-T细胞治疗:肝移植后复发hbv相关HCC的治疗方案
IF 11.5 1区 医学
Clinical Cancer Research Pub Date : 2025-07-24 DOI: 10.1158/1078-0432.ccr-25-1245
Qiang Zhao,Jinbo Huang,Weixin Luo,Haidong Tan,Regina Wan Ju Wong,Zhiying Liu,Meiting Qin,Jiahao Li,Sarene Koh,Lu-En Wai,Tingting Wang,Jia Dan,Zhiyong Guo,Xiaoshun He
{"title":"HBV-Specific TCR-T Cell Therapy Combining mRNA Electroporation and Lentiviral Transduction: Treatment Regime for Recurrent HBV-Related HCC Post-Liver Transplantation.","authors":"Qiang Zhao,Jinbo Huang,Weixin Luo,Haidong Tan,Regina Wan Ju Wong,Zhiying Liu,Meiting Qin,Jiahao Li,Sarene Koh,Lu-En Wai,Tingting Wang,Jia Dan,Zhiyong Guo,Xiaoshun He","doi":"10.1158/1078-0432.ccr-25-1245","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-1245","url":null,"abstract":"BACKGROUND & AIMSThis study aimed to preliminarily evaluate the safety, tolerability, and antitumor efficacy of HBV-specific TCR-T cell therapy combining mRNA electroporation and lentiviral transduction in patients with recurrent HBV-HCC post-LT.METHODSIn this pilot study (NCT04677088), two types of autologous HBV-specific TCR-redirected T cells were assessed without prior lymphodepletion: (1) multiple infusions of mRNA-electroporated HBV-TCR-T cells (mRNA-HBV-TCR-T cells) and (2) one to three infusions of lentiviral-transduced HBV-TCR-T cells (lenti-HBV-TCR-T cells). Treatment-related adverse events were assessed using the Common Terminology Criteria for Adverse Events (CTCAE), and anti-tumor efficacy was evaluated using computed tomography (CT) imaging according to RECIST 1.1 criteria. Progression-free survival (PFS) was defined as the time from the start of study treatment until objective tumor progression or death.RESULTSBoth mRNA-electroporated and lentiviral-transduced HBV-specific TCR-T cells demonstrated a favorable safety profile, with only Grade 1 to 2 treatment-related adverse events observed. In the mRNA-HBV-TCR-T cells cohort, the median PFS was 2.32 months (range: 1.87 to 2.77 months). The combination therapy cohort (mRNA-HBV-TCR-T cells + lenti-HBV-TCR-T cells) showed median PFS of 7.34 months (range: 4.47 to 7.60 months). CT imaging indicated effective tumor control in the combination therapy group.CONCLUSIONSThis study preliminarily suggests that the combination of mRNA-HBV-TCR-T cells and lenti-HBV-TCR-T cells could be a safe and potentially effective approach for treating patients following liver transplantation in the context of lifelong immunosuppression drug administration. Further studies are needed to refine treatment strategies and assess long-term safety and efficacy in this special patient population.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"25 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular characterization of NUT carcinoma: a report from the NUT carcinoma registry. NUT癌的分子特征:一份来自NUT癌登记的报告。
IF 1 1区 医学
Clinical Cancer Research Pub Date : 2025-07-24 DOI: 10.1158/1078-0432.CCR-25-1071
Justin J Kim, Sara A Walton, Navin R Mahadevan, Jessica Haradon, Francesco Paoloni, Paul K Paik, Jamie E Chaft, Robert Hsu, Sarina A Piha-Paul, Pasi A Jänne, David A Barbie, Lynette M Sholl, Steven G Dubois, Glenn J Hanna, Geoffrey I Shapiro, Christopher A French, Jia Luo
{"title":"Molecular characterization of NUT carcinoma: a report from the NUT carcinoma registry.","authors":"Justin J Kim, Sara A Walton, Navin R Mahadevan, Jessica Haradon, Francesco Paoloni, Paul K Paik, Jamie E Chaft, Robert Hsu, Sarina A Piha-Paul, Pasi A Jänne, David A Barbie, Lynette M Sholl, Steven G Dubois, Glenn J Hanna, Geoffrey I Shapiro, Christopher A French, Jia Luo","doi":"10.1158/1078-0432.CCR-25-1071","DOIUrl":"https://doi.org/10.1158/1078-0432.CCR-25-1071","url":null,"abstract":"<p><strong>Purpose: </strong>NUT carcinoma (NC) is an underdiagnosed, poorly differentiated squamous cell cancer with a median survival of 6.7 months. Defined by NUTM1 fusions, NC enhances oncogene transcription, including MYC. We investigated the ability of standard next-generation sequencing (NGS) to identify NUTM1 fusions and describe additional molecular features of NC.</p><p><strong>Experimental design: </strong>This study included 116 NC patients whose tumors underwent broad-panel NGS (>80 genes) of DNA, ctDNA, and/or RNA fusion sequencing between 2013-2024. NGS reports and medical records were manually reviewed.</p><p><strong>Results: </strong>Of 116 patients (median age 38, 40.5% female), 84.5% had DNA, 12.1% had ctDNA, and 51.7% had RNA fusion testing. In a subset of 100 patients with DNA/ctDNA testing, 92.9% (n=79/85) had <10 pack-years/never-smoking history, and 58.8% (n=47/80) had a BRD4::NUTM1 fusion. Median TMB was 1.0 mut/Mb (range 0.0-16.0; n=71 known), and 19.7% (n=13/66) had PD-L1 expression ≥1%. DNA, ctDNA, RNA fusion, NUT IHC, and NUTM1 FISH detected NC fusions in 21.6%, 21.4%, 83.9%, 100.0%, and 91.9% of tests, respectively. Co-occurring pathogenic mutations included oncogenes PIK3CA, RET, FGFR3, and tumor suppressors ATM and BRCA1 (n=1 each). Secondary genes altered in >5% of NCs included LRP1B (10.4%), MLL2/KMT2D (8.0%), and FAT1 (5.5%); common pathways with mutated genes were epigenetic (57.0%), cell cycle (26.0%), and DNA repair (24.0%).</p><p><strong>Conclusions: </strong>Standard DNA NGS detects less than a quarter of NUT carcinomas; RNA-based fusion testing, or NUT IHC/NUTM1 FISH, should be routine for suspected NC. NCs are enriched in co-occurring epigenetic, cell cycle, and DNA repair alterations, warranting further evaluation.</p>","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":" ","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genomic and epigenomic ctDNA profiling in liquid biopsies from heavily pre-treated patients with DNA damage response-deficient tumors. DNA损伤反应缺陷肿瘤患者重度预处理后液体活检的基因组和表观基因组ctDNA谱分析
IF 11.5 1区 医学
Clinical Cancer Research Pub Date : 2025-07-24 DOI: 10.1158/1078-0432.ccr-25-1248
Ian M Silverman,Joseph D Schonoft,Benjamin Herzberg,Arielle Yablonovitch,Errin Lagow,Patrick C Fiaux,Pegah Safabakhsh,Sunantha Sethuraman,Danielle Ulanet,Julia Yang,Insil Kim,Paul Basciano,Michael Cecchini,Elizabeth Lee,Stephanie Lheureux,Elisa Fontana,Benedito A Carneiro,Jorge S Reis-Filho,Timothy A Yap,Michael Zinda,Ezra Y Rosen,Victoria Rimkunas
{"title":"Genomic and epigenomic ctDNA profiling in liquid biopsies from heavily pre-treated patients with DNA damage response-deficient tumors.","authors":"Ian M Silverman,Joseph D Schonoft,Benjamin Herzberg,Arielle Yablonovitch,Errin Lagow,Patrick C Fiaux,Pegah Safabakhsh,Sunantha Sethuraman,Danielle Ulanet,Julia Yang,Insil Kim,Paul Basciano,Michael Cecchini,Elizabeth Lee,Stephanie Lheureux,Elisa Fontana,Benedito A Carneiro,Jorge S Reis-Filho,Timothy A Yap,Michael Zinda,Ezra Y Rosen,Victoria Rimkunas","doi":"10.1158/1078-0432.ccr-25-1248","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-1248","url":null,"abstract":"PURPOSEThe development of DNA damage response (DDR)-directed therapies is a major area of clinical investigation, yet to date Poly (ADP-ribose) polymerase inhibitors (PARPi) remain the only approved therapy in this space. Major challenges to DDR-targeted therapies in the post-PARPi era are the context dependency of DDR alterations and the presence of pre-existing resistance in this heavily pre-treated population. Blood samples from patients with tumors harboring defects in DDR genes were evaluated the feasibility of liquid biopsy platform for detecting complex genomic events such as BRCA1/2 reversions, HRD signatures, PV allele status, and differentially methylated regions for accurate quantitation of TF.PATIENTS AND METHODSOverall, 173 patients enrolled in two Phase 1/2 clinical trials (TRESR; NCT04497116, ATTACC; NCT04972110) were selected. The pre-treatment circulating tumor DNA (ctDNA) samples were analyzed from these patients, harboring pathogenic variants (PVs) in DDR genes.RESULTSIn a phase I heavily pretreated patient population with DDR defects, ctDNA can detect complex genomic alterations (HRD, biallelic loss, complex reversions) that historically require tumor tissue biopsies. Within the cohort of BRCA-associated tumor types previously treated with PARPi or platinum, HRD reversions were detected in 44% of evaluable patients and included large genomic rearrangements leading to deletion of whole or partial exons which have been underrepresented in the literature due to technological limitations.CONCLUSIONSThis study showcases the genomic complexity of DDR-altered tumors as revealed through baseline ctDNA profiling, an understanding of which is crucial for the future clinical development of novel DDR-directed therapies and combinations.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"31 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Durvalumab versus physician's choice chemotherapy in recurrent ovarian clear cell adenocarcinoma (MOCCA/APGOT-OV2/GCGS-OV3): a multicenter, randomized, phase 2 trial. Durvalumab与医生选择化疗治疗复发性卵巢透明细胞腺癌(MOCCA/APGOT-OV2/ gggs - ov3):一项多中心、随机、2期试验
IF 11.5 1区 医学
Clinical Cancer Research Pub Date : 2025-07-24 DOI: 10.1158/1078-0432.ccr-25-0201
Natalie Y L Ngoi,Chel Hun Choi,Junxian Zhu,Diana Lim,Tuan Zea Tan,Haoyang Sun,Valerie Heong,Samuel G W Ow,Wen Yee Chay,Hee Seung Kim,Yi Wan Lim,Siew Eng Lim,Geraldine Goss,Jeffrey C Goh,Jae-Weon Kim,Michael Friedlander,Bee Choo Tai,Kidong Kim,David S P Tan
{"title":"Durvalumab versus physician's choice chemotherapy in recurrent ovarian clear cell adenocarcinoma (MOCCA/APGOT-OV2/GCGS-OV3): a multicenter, randomized, phase 2 trial.","authors":"Natalie Y L Ngoi,Chel Hun Choi,Junxian Zhu,Diana Lim,Tuan Zea Tan,Haoyang Sun,Valerie Heong,Samuel G W Ow,Wen Yee Chay,Hee Seung Kim,Yi Wan Lim,Siew Eng Lim,Geraldine Goss,Jeffrey C Goh,Jae-Weon Kim,Michael Friedlander,Bee Choo Tai,Kidong Kim,David S P Tan","doi":"10.1158/1078-0432.ccr-25-0201","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-0201","url":null,"abstract":"PURPOSEThe optimal treatment of recurrent ovarian clear cell carcinoma (rOCCC) remains unknown. This is the first randomized trial to compare durvalumab with chemotherapy in rOCCC.PATIENTS AND METHODSMOCCA is a randomized, phase 2 trial conducted in Singapore, Korea and Australia. Eligible patients had rOCCC with recurrence after platinum-based chemotherapy, ECOG performance status ≤2 and no prior immune checkpoint blockade. Patients were randomly assigned (2:1) to durvalumab (1500mg every 4 weeks) or chemotherapy. Patients progressing on chemotherapy were allowed to crossover to durvalumab. The primary outcome was progression-free survival (PFS). Secondary outcomes included overall survival (OS), objective response rates (ORR), and safety.RESULTS48 eligible women were assigned to durvalumab (N= 31) or chemotherapy (N= 17). Median PFS was 7.6 (95% CI 7.0-16.0) and 14.0 (95% CI 7.0-32.9) weeks with durvalumab or chemotherapy, (HR 1.6, 95% CI 0.8-3.0; P= 0.92). Median OS was 37.9 (95% CI 21.7-143.0) and 40.6 (95% CI 25.0-not reached) weeks, respectively (HR 1.5, 95% CI 0.7-3.3; P= 0.85). The difference in ORR between groups was not statistically significant (durvalumab 9.7% vs PCC 18.8%; difference -9.1%, 95% CI -31.3%-12.9%; P= 0.83). Fewer all-grade (35.5% vs 68.8%) and high-grade (9.7% vs 31.3%) treatment-related adverse events were observed for durvalumab. PD-L1 CPS+ was observed in 28.9% (CPS≥1%) and 10.5% (CPS≥10%) of patients. PIK3CA mutations were associated with time to progression on durvalumab ³12 weeks (RR(-mutated vs -wildtype) 2.83, 95% CI 1.16 to 14.17).CONCLUSIONSDurvalumab was well-tolerated, but did not improve efficacy outcomes compared with chemotherapy in rOCCC.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"110 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Oxford Classic-defined EMT risk stratification of High Grade Serous Ovarian cancer for guiding treatment decisions. 牛津经典定义的高级别浆液性卵巢癌EMT风险分层用于指导治疗决策。
IF 11.5 1区 医学
Clinical Cancer Research Pub Date : 2025-07-24 DOI: 10.1158/1078-0432.ccr-24-4250
Lena Rai,Antonella Ravaggi,Eliana Bignotti,Robert L Hollis,Dale W Garsed,Ahwan Pandey,Kyriaki Barbara Papalois,Faheemah Patel,Yasmin Kamel,Leticia Campo,Alistair Easton,Joel Nulsen,Breeshey Roskams-Hieter,Mara Artibani,Lili Wang,Nosheen Hussain,Luyao Wang,Nancy Zaarour,Aneesh Aggarwal,Amro Ahmed-Ebbiary,Aws Al-Deka,Michael Churchman,C Simon Herrington,Laura Ardighieri,Federico Ferrari,Christopher Yau,Charlie Gourley,Franco Odicino,Ahmed Ashour Ahmed
{"title":"Oxford Classic-defined EMT risk stratification of High Grade Serous Ovarian cancer for guiding treatment decisions.","authors":"Lena Rai,Antonella Ravaggi,Eliana Bignotti,Robert L Hollis,Dale W Garsed,Ahwan Pandey,Kyriaki Barbara Papalois,Faheemah Patel,Yasmin Kamel,Leticia Campo,Alistair Easton,Joel Nulsen,Breeshey Roskams-Hieter,Mara Artibani,Lili Wang,Nosheen Hussain,Luyao Wang,Nancy Zaarour,Aneesh Aggarwal,Amro Ahmed-Ebbiary,Aws Al-Deka,Michael Churchman,C Simon Herrington,Laura Ardighieri,Federico Ferrari,Christopher Yau,Charlie Gourley,Franco Odicino,Ahmed Ashour Ahmed","doi":"10.1158/1078-0432.ccr-24-4250","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-4250","url":null,"abstract":"PURPOSEThe association between epithelial to mesenchymal transition in High Grade Serous Ovarian Cancer (HGSOC) and poor prognosis is known. However, molecularly defining a subset of tumours that reproducibly associates with poor prognosis has been an elusive goal in this disease. A molecular signature that can robustly identify patients with poor prognosis and guide treatment decisions, including surgical strategy and targeted therapies, can improve survival rates.EXPERIMENTAL DESIGNWe carried out RNA sequencing of 139 tumour samples (Brescia cohort), an external validation on 362 and 126 patients from the Scottish and Garsed cohort, respectively; and meta-analysis of 1023 tumours to develop clinically useful risk groups. Identification of therapeutic targets was carried out by transcriptomic analyses of FLOW-sorted tumour epithelial cells from fresh tumours and multiplex IF assessment of tissue sections.RESULTSIn this study we have validated the prognostic strength of the OxC-EMT in three independent patient cohorts- Brescia [HR=3.6 (95% CI=1.59-7.97), p=1.99e-03], Scottish [HR=1.71 (95% CI=1.08-2.70), p=2.23e-02] and Garsed [Kruskal-Wallis p=0.00071]. OxC-based risk-stratification of HGSOC can robustly identify poor risk patients with a 5-year median survival for OxC-EMT-high and OxC-EMT-low risk groups of 13% and 50%, respectively (95%CI: 7.1%-23.5% vs. 36.1%-69.3%) in the Brescia cohort. Further analysis of the risk groups suggests that an alternate surgical strategy and a combination therapy involving EMT targeting drugs and immunomodulators could elicit improved clinical response in poor risk patients.CONCLUSIONSThis study provides a clinically useful risk stratification strategy for HGSOC as well as targeted treatment options for high-risk patients.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"14 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Polyamine Depletion by D, L-alpha-difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis. D, l - α -二氟甲基鸟氨酸多胺耗竭诱导铁下垂抑制尤文氏肉瘤转移
IF 10.2 1区 医学
Clinical Cancer Research Pub Date : 2025-07-24 DOI: 10.1158/1078-0432.CCR-24-1778
Rachel Offenbacher, Kyle W Jackson, Masanori Hayashi, Jinghang Zhang, Da Peng, Yuqi Tan, Tracy Murray Stewart, Paul Ciero, Jackson Foley, Robert A Casero, Patrick Cahan, David M Loeb
{"title":"Polyamine Depletion by D, L-alpha-difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis.","authors":"Rachel Offenbacher, Kyle W Jackson, Masanori Hayashi, Jinghang Zhang, Da Peng, Yuqi Tan, Tracy Murray Stewart, Paul Ciero, Jackson Foley, Robert A Casero, Patrick Cahan, David M Loeb","doi":"10.1158/1078-0432.CCR-24-1778","DOIUrl":"10.1158/1078-0432.CCR-24-1778","url":null,"abstract":"<p><strong>Purpose: </strong>Despite decades of clinical trials, no progress has been made in improving the survival of patients with Ewing sarcoma who either present with metastatic disease or suffer a metastatic relapse. In our preclinical models, we found differential levels of polyamines in tumors that metastasize compared to tumors that do not, leading us to investigate the potential for D, L-alpha-difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis, to prevent Ewing sarcoma metastasis.</p><p><strong>Methods: </strong>The effect of DFMO on Ewing sarcoma cell lines in vitro was studied by measuring proliferation, sphere formation, and clonogenic growth in soft agar. The effect in vivo was investigated using our orthotopic implantation/amputation model of metastasis. Transcriptomic changes were evaluated by RNA sequencing.</p><p><strong>Results: </strong>DFMO causes a cell cycle arrest and inhibits both sarcosphere formation and clonogenic growth in soft agar. In vivo, DFMO slows primary tumor growth and inhibits metastasis. RNA sequencing demonstrated gene expression patterns consistent with induction of ferroptosis caused by polyamine depletion, which was validated in vitro by demonstrating that DFMO treatment induces lipid peroxidation and ferrostatin-1 and liproxstatin-1 allow sphere formation even in the presence of DFMO.</p><p><strong>Conclusion: </strong>DFMO slows the growth of Ewing sarcoma cells in vitro, with a profound impact on sphere formation and clonogenic growth, and impacts all aspects of Ewing sarcoma tumorigenesis, including tumor initiation, tumor growth, and metastasis, probably through induction of ferroptosis mediated by polyamine depletion. Our results provide preclinical justification to test the ability of DFMO to prevent metastatic recurrence in Ewing sarcoma patients.</p>","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cadonilimab (a PD-1/CTLA-4 bispecific antibody) Plus Neoadjuvant Chemotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase Ⅱ Clinical Trial. 卡多尼利单抗(PD-1/CTLA-4双特异性抗体)加新辅助化疗治疗局部晚期头颈部鳞状细胞癌:Ⅱ期临床试验
IF 11.5 1区 医学
Clinical Cancer Research Pub Date : 2025-07-24 DOI: 10.1158/1078-0432.ccr-25-1445
Fei Cao,Yan Li,Qi Fang,Ruobin Lin,Zheng Zhao,Pengfei Xu,Honghong Yan,Xinrui Zhang,Ke Jiang,Jian Zhou,Chunyan Chen,Lixia Lu,Fei Han,Zhiming Li,Di Wu,Xuekui Liu
{"title":"Cadonilimab (a PD-1/CTLA-4 bispecific antibody) Plus Neoadjuvant Chemotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase Ⅱ Clinical Trial.","authors":"Fei Cao,Yan Li,Qi Fang,Ruobin Lin,Zheng Zhao,Pengfei Xu,Honghong Yan,Xinrui Zhang,Ke Jiang,Jian Zhou,Chunyan Chen,Lixia Lu,Fei Han,Zhiming Li,Di Wu,Xuekui Liu","doi":"10.1158/1078-0432.ccr-25-1445","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-1445","url":null,"abstract":"PURPOSEPreclinical and clinical findings suggest that programmed cell death protein 1 (PD-1) /cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) bispecific antibodies may offer synergistic anti-tumor activity. This study aimed to explore the efficacy and safety of cadonilimab combined with neoadjuvant chemotherapy in locally advanced, resectable head and neck squamous cell carcinoma (HNSCC).PATIENTS AND METHODSEligible patients were consecutively enrolled and received cadonilimab (10 mg/kg) and chemotherapy (docetaxel, 75 mg/m2 plus cisplatin, 60 mg/m2) every 3 weeks for three cycles. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), pathological complete response (PCR), major pathological response (MPR), safety, progression-free survival (PFS), and overall survival (OS). Analyses of biomarkers and tumor-infiltrating immune cell subsets were conducted. This study is registered with ClinicalTrials.gov (NCT06023875).RESULTSThirty patients were included from July 2023 to December 2023. The median age was 55 years (range: 26-69) and 27 patients (90.0%) were male. The ORR was 83.3%, DCR was 100.0%, MPR rate was 76.7% and PCR rate was 50.0%. All patients experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs were reported in 7 (23.3%) patients. PFS and OS data were not yet mature as of the cutoff date (February 1,2025). Subgroup analysis revealed no significant differences in biomarker expression. A higher baseline infiltration of M1-like macrophage in the tumor stroma was associated with better treatment efficacy.CONCLUSIONSCadonilimab plus neoadjuvant chemotherapy demonstrated favorable ORR and MPR with manageable toxicities in patients with HNSCC.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"115 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
FDA approval summary: Lifileucel for unresectable or metastatic melanoma previously treated with an anti-PD-1 based immunotherapy. FDA批准概要:Lifileucel用于既往用抗pd -1免疫疗法治疗的不可切除或转移性黑色素瘤。
IF 11.5 1区 医学
Clinical Cancer Research Pub Date : 2025-07-23 DOI: 10.1158/1078-0432.ccr-25-0880
Lianne Hu,Chaohong Fan,Peter Bross,Asha Das,Elin S Cho,Karin M Knudson,Million Tegenge,Qianmiao Gao,Jamie R Brewer,Marc R Theoret,Lola A Fashoyin-Aje
{"title":"FDA approval summary: Lifileucel for unresectable or metastatic melanoma previously treated with an anti-PD-1 based immunotherapy.","authors":"Lianne Hu,Chaohong Fan,Peter Bross,Asha Das,Elin S Cho,Karin M Knudson,Million Tegenge,Qianmiao Gao,Jamie R Brewer,Marc R Theoret,Lola A Fashoyin-Aje","doi":"10.1158/1078-0432.ccr-25-0880","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-0880","url":null,"abstract":"On February 16, 2024, the FDA granted accelerated approval to lifileucel (Amtagvi, Iovance Biotherapeutics, Inc.) indicated for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. Lifileucel is the first tumor-derived T-cell therapy approved by the FDA. In the pivotal cohort of the phase 2 single-arm, trial, Study C-144-01, that served as the basis for approval, the objective response rate (ORR) among patients treated with lifileucel within FDA-approved dose range (7.5 x 109 - 72 x 109 viable cells, n=73) in the primary efficacy cohort was 31.5% (95% CI: 21.1%-43.4%), including 3 (4.1%) complete responses and 20 (27.4%) partial responses. The median duration of response was not reached (95% CI: 4.1 months-not reached). Among the responders (n=23), 56.5%, 47.8%, and 43.5% maintained durable responses at 6, 9, and 12 months, respectively. Among all patients who received lifileucel (N=156), 95.5% of patients experienced at least one Grade 3 treatment-emergent adverse event (TEAE) and 87.8% experienced at least one Grade 4 TEAE. Lifileucel labeling includes a Boxed Warning for treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary impairment, and renal impairment.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"23 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Circulating tumor DNA as a molecular biomarker in the phase II trial of imatinib plus binimetinib in patients with advanced gastrointestinal stromal tumors. 循环肿瘤DNA作为分子生物标志物在伊马替尼加比尼替尼治疗晚期胃肠道间质瘤患者的II期临床试验
IF 11.5 1区 医学
Clinical Cancer Research Pub Date : 2025-07-22 DOI: 10.1158/1078-0432.ccr-25-0145
Ciara M Kelly,Martina Bradic,Sara Saunds,Viswatej Avutu,Lauren Banks,Jason Chan,Sandra P D'Angelo,Mark A Dickson,Mrinal M Gounder,Mary Louise Keohan,Robert G Maki,Sujana Movva,Evan Rosenbaum,Ned Bartlett,Aimee M Crago,Brian R Untch,Vivian Strong,Samuel Singer,Sinchun Hwang,Cristina R Antonescu,Karthigayini Sivaprakasam,Maria Lapshina,Maysun Hasan,Ronak Shah,Michael F Berger,Li-Xuan Qin,William D Tap,Ping Chi
{"title":"Circulating tumor DNA as a molecular biomarker in the phase II trial of imatinib plus binimetinib in patients with advanced gastrointestinal stromal tumors.","authors":"Ciara M Kelly,Martina Bradic,Sara Saunds,Viswatej Avutu,Lauren Banks,Jason Chan,Sandra P D'Angelo,Mark A Dickson,Mrinal M Gounder,Mary Louise Keohan,Robert G Maki,Sujana Movva,Evan Rosenbaum,Ned Bartlett,Aimee M Crago,Brian R Untch,Vivian Strong,Samuel Singer,Sinchun Hwang,Cristina R Antonescu,Karthigayini Sivaprakasam,Maria Lapshina,Maysun Hasan,Ronak Shah,Michael F Berger,Li-Xuan Qin,William D Tap,Ping Chi","doi":"10.1158/1078-0432.ccr-25-0145","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-0145","url":null,"abstract":"PURPOSEThis study investigated factors that affected ctDNA detection and ctDNA as a molecular biomarker in a phase II trial of imatinib and binimetinib in newly diagnosed advanced GIST, including patients exposed to imatinib within 4 weeks of trial enrollment.EXPERIMENTAL DESIGNPlasma and tumor tissue samples were collected at baseline, on-treatment, and upon progression. DNAs extracted from plasma and tumor tissue were analyzed using genomic assays, MSK-ACCESS and MSK-IMPACT, respectively. Sequenced ctDNA detection of the primary oncogenic driver was determined and correlated with clinical characteristics.RESULTSPatients (n=31) included in this analysis had KIT mutant (n=29, 94%), metastatic disease (n=24, 77%), and achieved the best response of partial response (n=22, 71%), stable (n=8, 26%) or progressive disease (n=1, 3%). Sixteen patients (52%) were exposed to imatinib at baseline. The ctDNA detection rate of the primary oncogenic driver at baseline was 39% (n=12/31), and significantly more likely in patients that were treatment-naïve (n=15) or had ≤4.2 weeks of treatment (n=8) than otherwise (48% versus 13%, p-value = 0.004). Baseline ctDNA detection did not correlate with tumor burden or stage. The ctDNA serial analysis of the primary oncogenic driver paralleled and sometimes preceded radiographic response. CtDNA detected resistance mutations in KIT (n=4). Active treatment influenced detection of secondary KIT alterations in one patient.CONCLUSIONSActive therapy at the time of ctDNA collection negatively affected the ability to detect primary and secondary KIT alterations in sequenced ctDNA from patients with advanced GIST. CtDNA responses may precede radiographic responses, and merits further investigation.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"15 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Timing of Recurrence After Neoadjuvant Chemo-Immunotherapy in Early-Stage Triple-Negative Breast Cancer. 早期三阴性乳腺癌新辅助化疗-免疫治疗后复发的时机。
IF 11.5 1区 医学
Clinical Cancer Research Pub Date : 2025-07-21 DOI: 10.1158/1078-0432.ccr-25-1478
Luca Licata,Marco Mariani,Giulia Viale,Rebecca Dent,Sara M Tolaney,Peter Schmid,Erika Hamilton,Christos Sotiriou,Lajos Pusztai,Giampaolo Bianchini
{"title":"Timing of Recurrence After Neoadjuvant Chemo-Immunotherapy in Early-Stage Triple-Negative Breast Cancer.","authors":"Luca Licata,Marco Mariani,Giulia Viale,Rebecca Dent,Sara M Tolaney,Peter Schmid,Erika Hamilton,Christos Sotiriou,Lajos Pusztai,Giampaolo Bianchini","doi":"10.1158/1078-0432.ccr-25-1478","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-1478","url":null,"abstract":"INTRODUCTIONNeoadjuvant chemo-immunotherapy for high-risk triple-negative breast cancer (TNBC) has been shown to reduce the risk of recurrence and improve survival. However, the prognosis for patients with metastatic TNBC remains poor, especially for those with an early recurrence, who represent an urgent unmet need. Defining the most common timing of recurrences after chemo-immunotherapy is crucial for shaping the design of future clinical trials.METHODSWe analyzed five clinical trials of neoadjuvant chemo-immunotherapy in early-stage TNBC to quantify the contribution of early recurrences (within 24 months from randomization) to the overall risk of relapse. Event-free survival data were extracted from Kaplan-Meier curves using PlotDigitizer. Events were evaluated up to 48 months, a time frame with consistent follow-up across trials and minimal later events. The primary endpoint was the proportion of early versus total recurrences by 48 months; secondary analyses stratified this by pathological complete response status.RESULTSOverall recurrence rates by 48 months in the immunotherapy arms were: 14.3% (GeparNuevo), 14.8% (NSABP-B59/GeparDouze), 17.5% (KEYNOTE-522), 20.2% (IMpassion031), and 29.2% (NeoTRIP). The proportion of early relapse ranged from 64.6% in NSABP-B59/GeparDouze to 82.9% in GeparNuevo. This proportion was higher in patients with residual disease after neoadjuvant therapy (range 69.4% to 88.6%). Patients who achieved a pathological complete response showed a similar proportion of early and late events.CONCLUSIONSRecurrences within 24 months account for majority of recurrences in TNBC patients who relapse after neoadjuvant chemo-immunotherapy. Clinical trials are needed to define the optimal therapy for this patient population.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"14 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信