Clinical Cancer Research最新文献

{"title":"Neoadjuvant BMS-813160, nivolumab, gemcitabine and nab-paclitaxel for patients with pancreatic cancer","authors":"Patrick M. Grierson, Crystal Wolf, Rama Suresh, Andrea Wang-Gillam, Benjamin R. Tan, Lee Ratner, Peter Oppelt, Olivia Aranha, Ashley Frith, Katrina S. Pedersen, Jennifer Spann, Nicholas Boice, Amberly Brown, John M. Baer, Emily G. Butka, Faiz Ahmad, Yifei Xu, Jingxia Liu, David G. DeNardo, Kian-Huat Lim","doi":"10.1158/1078-0432.ccr-24-1821","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-1821","url":null,"abstract":"Background: Targeting tumor-associated macrophages through C-C chemokine receptor type 2 (CCRs) in pancreatic ductal adenocarcinoma (PDAC) improves the efficacy of chemotherapy and restores T cell immunity in preclinical models. Methods: We conducted a phase I/II single institution study (NCT03496662) combining chemotherapy gemcitabine and nab-paclitaxel (GnP), CCR2/5 inhibitor BMS-813160 and nivolumab for four 28-day cycles for patients with borderline resectable (BR) or locally advanced (LA) PDAC. The recommended phase 2 dose (RP2D) of BMS-813160 was established in the 3+3 design. Primary endpoints were safety and objective response rate (ORR). Secondary endpoints included resection rate, median progression-free survival (mPFS) and overall survival (mOS). Results: 8 patients were treated with GnP alone (control arm) and 31 patients (29 response evaluable) were treated at RP2D. No grade 3/4 toxicities attributed to nivolumab or BMS-813160 were identified. After 4 cycles of study treatment (N=26), ORR was 35.7% and 16.7% among BR- and LA-PDAC patients respectively, compared to 0% of control patients. 78.6% BR- and 16.7% of LA-PDAC patients who completed study treatment underwent surgical resection. For intent-to-treat analyses, BR-PDAC patients had a mPFS and mOS of 14.6 and 20.4 months respectively; and for LA-PDAC patients, were 14.7 and 17 months, respectively. Biomarker analyses showed decreased intratumoral monocytes, macrophages, enhanced T cell proliferation and effector gene expression. Conclusions: Neoadjuvant BMS-813160/nivolumab/GnP was well tolerated and appears to achieve comparable ORR and resectability to historical data, however with prolonged PFS and OS in LA-PDAC patients, warranting a larger phase II study with a more efficacious CCR2-targeted therapeutic.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"45 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677646","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}

{"title":"Riluzole in Combination with mFOLFOX6 and Bevacizumab in Treating Patients with Metastatic Colorectal Cancer: A Phase 1 Clinical Trial","authors":"Chunjie Li, Anne M. Noonan, John Hays, Sameek Roychowdhury, Pannaga Malalur, Rifat Elkhatib, Ashish Manne, Arjun Mittra, Shafia Rahman, Liwei Yan, Kasey Hill, Nicole Abbott, Mitch Phelps, Joo Young Na, Beiyuan Liang, Hayden Storts, Misbah Khan, Evan H. Zhang, Wayne Miles, Vedat Yildiz, Lai Wei, Jing J. Wang, Ning Jin","doi":"10.1158/1078-0432.ccr-24-3964","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-3964","url":null,"abstract":"BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the US. 5-fluorouracil (5-FU)-based chemotherapies in combination with targeted agents remain the standard of care in patients with metastatic or locally advanced disease. New treatment strategies are needed for metastatic CRC patients with microsatellite stable disease. Preclinical studies showed that riluzole, an oral medicine for amyotrophic lateral sclerosis, inhibits glutamate release and synergizes with 5-FU to reduce cell viability in CRC cell lines. METHODS: In this single-arm, phase 1 trial of riluzole in combination with mFOLFOX6/bevacizumab for patients with metastatic CRC, the riluzole dose started at 50 mg twice daily, escalating to 100 mg twice daily or de-escalating to 50 mg once daily. Patients received riluzole for 16 weeks in combination with mFOLOFX6/bevacizumab for 8 cycles. Patients then either continued mFOLFOX6/bevacizumab or switched therapy. RESULTS: Twelve of the 14 patients enrolled were evaluable. All patients previously received FOLFOX, and 5 patients (41.7%) showed disease resistance to it. Two patients obtained partial responses, 9 had stable disease, and 1 had progressive disease. The objective response rate was 16.7%, and the disease control rate was 91.7%. The median duration of response was 4.9 months (95% CI 1.6-9.8). Median progression-free survival and overall survival were 4.89 and 12.98 months, respectively. CONCLUSION: Our study showed that riluzole plus mFOLFOX6/bevacizumab is well tolerated in patients with metastatic CRC and may have clinical activity in patients whose disease is resistant to FOLFOX.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"49 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665863","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}

{"title":"Detection of circulating tumor DNA using a tissue-free epigenomic assay is a highly prognostic biomarker in early-stage triple negative breast cancer","authors":"Foluso O. Ademuyiwa, Cynthia X. Ma, Katherine Weilbaecher, Rama Suresh, Lindsay L. Peterson, Ron Bose, Nusayba Bagegni, Caron E. Rigden, Ashley Frith, Katherine Clifton, Derek Dustin, Mingyang Cai, Liyang Xiong, Sai Chen, Andrew Davis","doi":"10.1158/1078-0432.ccr-24-3145","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-3145","url":null,"abstract":"Purpose: Clinical tools to monitor treatment response and metastatic risk could improve early-stage triple-negative breast cancer (TNBC) care. While molecular residual disease (MRD) assays show promise, their use in the neoadjuvant setting requires rapid turnaround times. Tissue-informed approaches may be challenging for patients with limited biopsy samples. The objectives were to determine the surveillance sensitivity for detecting metastatic recurrence and evaluate the ctDNA response to neoadjuvant therapy using a tissue-free epigenomic assay. Patients and Methods: Patients with stage II or III TNBC undergoing neoadjuvant docetaxel and carboplatin chemotherapy on a clinical trial (NCT02124902) followed by surgery with or without adjuvant therapy were included in this study. Blood samples were prospectively collected prior to, during, and after completion of neoadjuvant therapy (NAT), and after surgery at pre-specified surveillance time points. Plasma samples were analyzed by Guardant Reveal. Results: A total of 119 TNBC patients were included in the analysis. ctDNA was detected in the post-surgical setting in 8.9% (7/79) of patients, with an 83% (5/6) patient-level surveillance sensitivity for metastatic recurrence and 99.5% (197/198) sample-level specificity. Post-surgical ctDNA detection was prognostic for shorter recurrence-free interval (RFI; HR 37.7, p<0.0001). ctDNA detection at the post-NAT pre-surgical time point was also associated with shorter RFI in patients with residual disease at surgery (HR 28.2, p<0.0001). Conclusions: In early-stage TNBC patients, a tissue-free, epigenomic assay and demonstrated high specificity and sensitivity for metastatic recurrence. ctDNA detection in the neoadjuvant setting indicated poor prognosis, highlighting its potential role across breast cancer care.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"92 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672356","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}

{"title":"Facts and hopes of CD40 agonists as a cancer immunotherapy","authors":"John C. McVey, Gregory L. Beatty","doi":"10.1158/1078-0432.ccr-24-1660","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-1660","url":null,"abstract":"CD40 agonists are a promising class of immunotherapeutic agents that potentiate both innate and adaptive immunity. This review examines the established facts and prospects of CD40 agonists in cancer immunotherapy. CD40, a co-stimulatory receptor of the TNF receptor superfamily, is found on antigen-presenting cells. CD40 activation licenses dendritic cells to prime tumor-specific T cells, polarizes macrophages to a pro-inflammatory phenotype, activates B cells, and facilitates tumor fibrosis remodeling. Preclinical models demonstrate the significant potential of CD40 agonists to induce anti-tumor immunity, leading to the development of various CD40-activating therapeutics, including monoclonal antibodies, recombinant CD40L, and ectopic expression of CD40L via gene transfer. While clinical trials show modest antitumor activity, some patients experience durable responses, especially when CD40 agonists are combined with other therapies such as immune checkpoint inhibitors and chemotherapy. These combinations, tested in traditionally difficult-to-treat cancers like pancreatic cancer, provide hope for improved outcomes. Current research focuses on refining CD40 agonist therapies through novel combination strategies, improving patient selection, and the development of tumor-targeted CD40 agonists and Fc-engineered antibodies which aim to enhance efficacy while mitigating toxicity. However, significant challenges remain, particularly in identifying patients most likely to benefit from CD40 immunotherapy and understanding resistance mechanisms. Addressing these challenges is crucial for guiding effective combination strategies and optimizing treatment outcomes. By examining both established facts and ongoing developments, this review provides a comprehensive overview of the status and potential of CD40 agonists in cancer immunotherapy.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"22 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672338","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}

{"title":"Precision Endocrine Therapy in Endometrial Cancer: Has its time finally come?","authors":"Vikas Garg, Amit M. Oza","doi":"10.1158/1078-0432.ccr-24-3905","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-3905","url":null,"abstract":"Endocrine therapy (ET) has been underexplored in endometrial cancer (EC). Emerging data suggest that combining ET with CDK4/6 inhibitors improve outcomes in EC. This commentary complements a recent CCR manuscript and reviews opportunities to improve precision ET, and the potential to overcome resistance mechanisms associated with ET failure.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"20 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672339","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}

{"title":"A phase 1 study of nilotinib in combination with paclitaxel in patients with advanced solid tumors.","authors":"Sarah J Shin, Geraldine O'Sullivan Coyne, Shivaani Kummar, Sarah B Miller, Barry C Johnson, Larry Anderson, Larry Rubinstein, Brandon Miller, Deborah F Wilsker, Katherine V Ferry-Galow, Richard Piekarz, Jennifer Zlott, Murielle Hogu, Lamin Juwara, Julia Krushkal, Mariam Konaté, Alida Palmisano, Yingdong Zhao, Jerry Collins, Ralph E Parchment, James H Doroshow, Alice P Chen","doi":"10.1158/1078-0432.CCR-24-3049","DOIUrl":"https://doi.org/10.1158/1078-0432.CCR-24-3049","url":null,"abstract":"<p><strong>Purpose: </strong>We assessed the safety, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), efficacy, pharmacokinetic, and pharmacodynamics of the nilotinib-paclitaxel combination in 44 patients with solid tumors.</p><p><strong>Patients and methods: </strong>Paclitaxel was administered intravenously (days 1, 8, and 15) and nilotinib was administered twice daily orally beginning on cycle 1 day 2 (C1D2, escalation) or C1D3 (expansion) in 28-day cycles using a 3+3 dose escalation design. Pharmacodynamic biomarkers of drug action were assessed in paired tumor biopsies and circulating tumor cells (CTCs) at the RP2D.</p><p><strong>Results: </strong>The RP2D was 300 mg nilotinib twice daily with 80 mg/m2 paclitaxel. Grade 4 (Gr4) neutropenia and Gr3 rash, photosensitivity, and transaminase elevation were dose-limiting. The most common Gr3-4 toxicities were hematological and hypophosphatemia; 1 patient (2%) experienced Gr3 peripheral neuropathy. Three patients (2 with adult ovarian granulosa cell tumors [AOGCT] and 1 with endometrial carcinoma) had confirmed partial responses (cPR); the patients with AOGCT remained on study for 5 and 6+ years and mesenchymal-like CTCs were measured prior to progression or during treatment holiday (patients 12 and 10, respectively).</p><p><strong>Conclusions: </strong>This study determined the MTD of this combination, demonstrated sustained cPRs in patients with AOGCT, and profiled molecular pharmacodynamic responses that will inform further mechanism of action studies. The rate of peripheral neuropathy suggests enhanced tolerability of this combination.</p>","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":" ","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656486","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}

{"title":"RECLASSIFICATION OF ATM MISSENSE VARIANTS OF UNCERTAIN SIGNIFICANCE BY INTEGRATING RESULTS FROM SYSTEMATIC FUNCTIONAL ASSAYS INTO AN ACMG POINTS-BASED FRAMEWORK.","authors":"Helmut Hanenberg, Fan Zhang, Nikita Malev, Constanze Wiek, Brett G Klamer, Nicolas Nassar, Tyler Hesselbrock, Judith H Hanenberg, Amber M Aeilts, Julia Hentschel, Ulrike Faust, Andrea Gehrig, Christoph Engel, Jan Hauke, Dieter Niederacher, Amanda E Toland, Paul R Andreassen","doi":"10.1158/1078-0432.CCR-24-3936","DOIUrl":"https://doi.org/10.1158/1078-0432.CCR-24-3936","url":null,"abstract":"<p><strong>Purpose: </strong>ATM is a moderate-risk cancer susceptibility gene which harbors thousands of missense variants of uncertain significance (VUS) that limit the power of clinical genetic testing for cancer risk management and personalized medicine. Functional tests provide a valuable basis for testing the impact of variants but have been lacking for ATM.</p><p><strong>Experimental design: </strong>We developed a systematic approach to functionally characterize missense ATM variants, based on correction of various DNA damage-related phenotypes, via re-expression of ATM in either of two ATM-deficient human cell lines.</p><p><strong>Results: </strong>A pKAP1 phospho-flow assay for ATM VUS observed in hereditary cancer patients was calibrated using 48 benign and pathogenic controls, achieving 100% specificity and 97% sensitivity. This system distinguished 82 of 88 (93%) missense ATM VUS of the FATKIN region as functionally neutral or deleterious. Importantly, for clinical classification of VUS, functional results were incorporated into an American College of Medical Genetics (ACMG) points-based framework, also considering conservation and properties of amino acids/substitutions, along with genetic data; 79 of 88 (90%) were thereby reclassified as benign/likely benign or pathogenic/likely pathogenic. As additional validation of our approach, clinical characteristics from a database of 1,134 breast cancer patients were distinct for carriers of neutral vs deleterious ATM variants. Also, utilizing our functional results we identified hotspots for deleterious VUS and controls at amino acids 2702-2730 and 2891-2951 of ATM.</p><p><strong>Conclusions: </strong>We have established functional assays as a reliable tool that will better interpret the clinical impact of ATM variants and guide improved cancer prevention measures for carriers.</p>","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":" ","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656487","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}

{"title":"Longitudinal Genomic Analysis to Fine-Tune Targeted Therapy: Results of the Phase II LOGIC 2 Trial in Patients With BRAF V600-Mutant Metastatic Melanoma","authors":"Reinhard Dummer, Shahneen Sandhu, Wilson H. Miller, Marcus O. Butler, Matthew H. Taylor, Lucie Heinzerling, Christian U. Blank, Eva Munoz-Couselo, Howard A. Burris, Michael A. Postow, Bartosz Chmielowski, Mark R. Middleton, Carola Berking, Jessica C. Hassel, Anja Heike. Gesierich, Cornelia Mauch, Joseph F. Kleha, Anna Polli, Allison S. Harney, Alessandra di Pietro, Paolo A. Ascierto","doi":"10.1158/1078-0432.ccr-24-0254","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-0254","url":null,"abstract":"Purpose: LOGIC 2 (NCT02159066), a multicenter, open-label, two-part, phase II study assessed encorafenib plus binimetinib combined with a third targeted agent after tumor progression on encorafenib plus binimetinib in patients with locally advanced unresectable or metastatic BRAF Patients and Methods: Adults with locally advanced unresectable or metastatic BRAF V600-mutant melanoma who were BRAF inhibitor/MEK inhibitor (BRAFi/MEKi)-treatment naive or pretreated received encorafenib plus binimetinib (Part I/Run-in). Based on the genomic testing at disease progression following encorafenib plus binimetinib, patients were assigned to one of four treatment arms to receive encorafenib plus binimetinib with an appropriate molecularly targeted agent (ribociclib, infigratinib, capmatinib, or buparlisib; Part II). The primary endpoint was best overall response; safety, biomarkers, pharmacokinetics, and other efficacy endpoints were also assessed. Results: In Part I/Run-in, 75 BRAFi/MEKi-naive patients and 83 BRAFi/MEKi-pretreated patients were treated; in Part II, 58 patients were treated (ribociclib, n=38; infigratinib, n=1; capmatinib, n=13; buparlisib, n=6). The overall confirmed response rate was 73.3% (95% CI, 61.9–82.9) in BRAFi/MEKi-naive patients, 25.3% (95% CI, 16.4–36.0) in pretreated patients, 2.6% (95% CI, 0.1–13.8) in the ribociclib arm, and 0% in the other three arms. Adverse events were manageable and consistent with the known safety profile of each drug. Conclusions: LOGIC 2 supports the use of encorafenib plus binimetinib for treatment naive and previously treated locally advanced unresectable or metastatic BRAF V600-mutant melanoma. However, adding a third targeted agent following disease progression did not show meaningful efficacy; further research is needed to identify other therapeutic targets to circumvent resistance.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"37 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661328","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}

{"title":"Phase I study of the mutant IDH1 inhibitor ivosidenib: long-term safety and clinical activity in patients with conventional chondrosarcoma","authors":"William D. Tap, Gregory M. Cote, Howard Burris, Lia Gore, Anthony Elias, Murali Beeram, Anthony P. Conley, Diego A. Gianolio, Zhe Qu, Susan Pandya, Jonathan C. Trent","doi":"10.1158/1078-0432.ccr-24-4128","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-4128","url":null,"abstract":"Purpose: A phase I study demonstrated that ivosidenib, a mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor, showed manageable toxicity and durable disease control in patients with mIDH1 conventional chondrosarcoma (CS). Here we present long-term follow-up data on the safety and clinical activity of ivosidenib in patients with mIDH1 conventional CS from this phase I study. Patients and Methods: This phase I open-label dose-escalation and expansion study assessed ivosidenib monotherapy in patients with advanced mIDH1 solid tumors, including CS. An ivosidenib dose of 500 mg/day was identified in the dose-escalation phase and used for the expansion phase. The primary outcome was safety and tolerability. Secondary outcomes included objective response rate (ORR) and progression-free survival (PFS). The database lock date for this analysis was 18 March 2024. Results: Of 168 patients with advanced mIDH1 solid tumors receiving ivosidenib in this study, 21 patients had CS, of which 13 had conventional histology. Six (46.2%), 4 (30.8%) and 3 (23.1%) patients with conventional CS continued ivosidenib treatment for &amp;gt;1 year, &amp;gt;6 years and &amp;gt;7 years, respectively. Of the 21 patients with CS, 71.4% and 28.6% had treatment-related and serious adverse events (SAEs), respectively, but no SAEs were considered related to ivosidenib. The ORR for patients with conventional CS was 23.1% and median duration of response was 53.5 months. The median PFS of patients with conventional CS treated with ivosidenib was 7.4 months. Conclusions: Ivosidenib demonstrated long-term disease control and manageable toxicity for some patients with mIDH1 conventional CS and is under further investigation (NCT06127407).","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"183 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653419","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}

{"title":"Bevacizumab, atezolizumab and acetylsalicylic acid in recurrent, platinum-resistant ovarian cancer: the EORTC 1508-GCG phase II study","authors":"Susana Banerjee, Eleonora Ghisoni, Anita Wolfer, Petronella Beatrix. Ottevanger, Ronan Le Scodan, Apostolos Sarivalasis, Ana Montes, Judith Kroep, Margarita Romeo Marin, Petr Szturz, Matteo Morotti, Julien Dagher, Lana Kandalaft, Fernanda Herrera, Corneel Coens, Denarda Dangaj Laniti, George Coukos","doi":"10.1158/1078-0432.ccr-24-3368","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-3368","url":null,"abstract":"Purpose: Treatment options for platinum-resistant ovarian cancer (PROC) are limited and new therapeutic strategies are urgently needed. This phase II, randomized, multicentre trial evaluated the safety and activity of the anti-PD-L1 antibody atezolizumab (atezo) combined with the VEGF-inhibitor bevacizumab (bev) and the irreversible cyclooxygenase inhibitor aspirin (ASA) in PROC. Patients and Methods: Patients were randomized to bev monotherapy 15 mg/kg (arm 1), atezo 1200 mg plus placebo (pbo)(arm 2), atezo plus ASA 320 mg/daily (arm 3), bev plus atezo plus pbo (arm 4) or bev plus atezo plus ASA (arm 5). Primary endpoint was progression-free survival at 6 months (PFS-6). Secondary objectives included overall survival (OS), PFS, PFS2 and tolerability. Time to first subsequent therapy (TFST) was evaluated in a post-hoc analysis. Results: In arms 1, 4 and 5, there were 7/32 (21.9%, 70% CI, 14.0-32.0), 8/32 (25.0%, 70% CI, 16.6-35.3), and 8/32 (25.0%, 70% CI, 16.6-35.3) patients alive and progression-free at 6 months. The primary objective was not reached in any arm. Median PFS were 2.3 for bev monotherapy, 4.1 for bev-atezo-pbo, and 4.0 months for bev-atezo-ASA. TFST suggested benefit of adding bev to atezo-ASA (p&amp;lt;0.001). Tumour-infiltrating lymphocytes (TILs) increased in the atezo containing arms and increased TILs were associated with longer TFST. Conclusions: The addition of ASA to bev-atezo was well tolerated but did not improve efficacy in PROC. Relative to bev, the bev-atezo combination numerically improved PFS. Exploratory analyses suggest clinical benefit in a subgroup of patients characterised by high TILs infiltration and PD-L1+ tumours at baseline.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"44 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653439","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}