Journal of Immunotherapy and Precision Oncology最新文献

{"title":"PD-L1 Testing, Treatment Patterns, and Clinical Outcomes Among Patients with Metastatic NSCLC at an Academic Medical Center, 2017-2021.","authors":"Mehmet Altan, Dawen Sui, Cai Xu, George R Simon, Saliha T Sulihem, Donna Malveaux, Darcy Ponce, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, J Jack Lee, Jianjun Zhang, Don L Gibbons, Ara A Vaporciyan, John V Heymach, Melissa L Santorelli, Thomas Burke, Loretta A Williams","doi":"10.36401/JIPO-24-26","DOIUrl":"https://doi.org/10.36401/JIPO-24-26","url":null,"abstract":"<p><strong>Introduction: </strong>Targeted therapies and immune checkpoint inhibitors (ICIs) have revolutionized the management of metastatic non-small cell lung cancer (NSCLC) over the past decade.</p><p><strong>Methods: </strong>This single-center observational study was conducted to describe programmed death-ligand 1 (PD-L1) testing, choice of therapy, and outcomes for adult patients with stage IV NSCLC initiating first-line therapy from 2017 through 2020, with follow-up through June 2021. Patient characteristics and study assessments were described according to four histomolecular subtypes, defined by histologic characteristics and availability of standard-of-care therapies for molecular subgroups at the time of study conduct.</p><p><strong>Results: </strong>Of 507 eligible patients with metastatic NSCLC, 85 (17%) had squamous NSCLC; 288 (57%) had nonsquamous NSCLC with no actionable genomic alteration; 44 (9%) had nonsquamous NSCLC with <i>KRAS</i> G12C mutation; and 90 (18%) had nonsquamous NSCLC with <i>ROS1</i>, <i>BRAF</i> V600E, <i>EGFR</i> exon 20 insertion, or <i>RET</i> or <i>NTRK</i> genomic alteration. Most tumors were PD-L1 tested. After excluding 40 patients whose PD-L1 testing status was unknown, all but 55 tumors (12%) were tested for PD-L1 expression, and the percentages tested rose from 86% in 2017 to 100% in 2020. From 27% of nonsquamous NSCLC with no actionable genomic alteration to 46% of <i>KRAS</i> G12C-mutated NSCLC had PD-L1 expression ≥ 50%. Use of chemotherapy decreased and use of ICI-chemotherapy combinations increased from 2017 to 2020. In the squamous NSCLC group, single or combination chemotherapy was administered most commonly (42%), whereas ICI-chemotherapy combinations were the most common first-line regimens in the three nonsquamous NSCLC histomolecular groups. For patients with NSCLC and no actionable genomic alterations, ICI-chemotherapy combinations were the most common regimens in 2018-2020 in all but the PD-L1 ≥ 50% category, for whom ICI monotherapy was most common every year except 2020. Median overall survival was 25.0 months (95% CI, 19.1-28.3) for all patients, and, by histomolecular cohort, 14.3 months for squamous NSCLC, 25.3 months for nonsquamous NSCLC with no actionable genomic alteration, not reached for <i>KRAS</i> G12C-mutated NSCLC, and 27.7 months for nonsquamous NSCLC with other genomic alterations.</p><p><strong>Conclusion: </strong>Study findings highlight the increased use of PD-L1 testing over the years from 2017 to 2020 and recent changes in therapy, with decreased use of chemotherapy and increased use of ICI-chemotherapy combinations during the study in each histomolecular group. Moreover, we observed improvements in survival for patients with metastatic NSCLC relative to historical real-world data.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"8 2","pages":"161-171"},"PeriodicalIF":0.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024135","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":"Major Adverse Cardiovascular Events in Patients with Melanoma Receiving Immune Checkpoint Inhibitors.","authors":"Juan I Ruiz, Bo Zhao, Nicolas Palaskas, Anita Deswal, Hui Zhao, Jennifer McQuade, Maria E Suarez-Almazor","doi":"10.36401/JIPO-24-31","DOIUrl":"https://doi.org/10.36401/JIPO-24-31","url":null,"abstract":"<p><strong>Introduction: </strong>Immune checkpoint inhibitors (ICIs) might increase the risk of major adverse cardiovascular events (MACEs). This study aimed to evaluate the risk of MACE in patients with melanoma after ICI initiation.</p><p><strong>Methods: </strong>We conducted a before-after cohort study using claims data from Optum's deidentified Clinformatics Data Mart Database. We included adult patients with melanoma who received any approved ICI between 2011 and 2021 with a minimum of 12 months of observable data before ICI. The main outcome was time to first MACE (myocardial infarction, coronary revascularization, stroke, heart failure hospitalization) and rate of MACE before and after ICI, ascertained using <i>International Classification of Diseases</i>, 9th/10th Revision diagnostic codes. Hazard ratio (HR) and incidence rate ratio (IRR) were calculated.</p><p><strong>Results: </strong>We identified 4024 patients with ICI-treated melanoma. Mean age was 67.4 years (SD 14.1), 36% were women; 3066 (76.2%) received monotherapy and 958 (23.8%) combination immunotherapy. A total of 160 (4%) patients had a MACE before ICI and 224 (5.6%) after ICI (HR, 1.76; 95% CI, 1.47-2.12). MACE rate in the year before ICI was 56.16 per 1000 person-years compared with 80.91 per 1000 person-years the year after ICI (IRR, 1.44; 95% CI, 1.21-1.72). Ten cases of myocarditis were observed after ICI, 50% of them had a MACE. Risk factors associated with MACE after ICI were prior MACE, other cardiovascular conditions, hypertension, and older age. Glucocorticoid use was not associated with MACE.</p><p><strong>Conclusion: </strong>Our results suggest that ICI might increase the risk of MACE in patients with melanoma during the first year after ICI.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"8 2","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11987079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021062","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":"Pembrolizumab in Patients with Advanced Miscellaneous Rare Cancers: Results from a Phase 2 Basket Trial.","authors":"Mirella Nardo, Camila Braganca Xavier, Bettzy Stephen, Jeffrey A How, Justin Moyers, Vivek Subbiah, David S Hong, Aung Naing","doi":"10.36401/JIPO-24-27","DOIUrl":"10.36401/JIPO-24-27","url":null,"abstract":"<p><strong>Introduction: </strong>Rare solid tumors account for one-quarter of cancers among adults in the United States, but few resources have been devoted to their treatment. We evaluated the efficacy of pembrolizumab, a programmed cell death-1 inhibitor, in patients with rare solid tumors.</p><p><strong>Methods: </strong>We conducted a phase 2 basket trial that included patients with rare, advanced tumors. Patients were enrolled in the study in nine tumor-specific and a 10th cohort of miscellaneous rare histologies. Patients received pembrolizumab 200 mg intravenously every 21 days. The primary endpoint was the non-progression rate at 27 weeks per immune-related Response Evaluation Criteria in Solid Tumors (RECIST). The secondary endpoints were confirmed objective response (immune-related complete response [irCR] or partial response [irPR]), clinical benefit (irCR, irPR, or immune-related stable disease [irSD] ≥ 4 months), safety, and tolerability. Pretreatment biopsy specimens were examined for programmed cell death ligand-1 combined positive score (CPS) and tumor-infiltrating lymphocyte status. Herein, we report the outcomes in 12 patients with miscellaneous rare histologies who were on the study between October 5, 2016, and August 30, 2019.</p><p><strong>Results: </strong>Twelve patients with rare cancers were enrolled from October 5, 2016, to August 30, 2019. The patients received a median of four lines of therapy before enrollment. Three patients (25%) remained free of progression at 27 weeks, one patient (8%) had an objective response, and five patients (42%) received clinical benefit. Six patients (50%) experienced at least one adverse event, of whom five (42%) experienced immune-related adverse events. The only grade ≥ 3 adverse event was non-immune-related anemia. Among the seven patients with CPS ≥ 1, one had irPR and two had irSD as the best response. Among the six patients with a CPS of 3, one had irPR and two had irSD as the best response.</p><p><strong>Conclusions: </strong>Single-agent pembrolizumab showed modest efficacy and was well tolerated in patients with rare solid tumors (ClinicalTrials.gov Identifier: NCT02721732).</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"8 2","pages":"143-151"},"PeriodicalIF":3.2,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022457","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":"Guest Editor and Reviewer Acknowledgments: 2024.","authors":"","doi":"10.36401/JIPO-25-X2","DOIUrl":"https://doi.org/10.36401/JIPO-25-X2","url":null,"abstract":"","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"8 2","pages":"152"},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999585","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":"B7 Homolog 4 (B7-H4)-Directed Agents in Oncology Clinical Trials: A Review.","authors":"Meave Phipps, Gerald S Falchook","doi":"10.36401/JIPO-24-34","DOIUrl":"https://doi.org/10.36401/JIPO-24-34","url":null,"abstract":"<p><p>B7 homolog 4 (B7-H4) is a transmembrane protein found on immune cells and is frequently overexpressed in various solid tumors, making it a promising target for cancer therapy. B7-H4-directed agents, particularly antibody-drug conjugates (ADCs) like puxitatug samrotecan (AZD8205), felmetatug vedotin (SGN-B7H4V), and GSK5733584, have demonstrated early clinical activity with promising response rates in triple-negative breast cancer (TNBC). Combination strategies, such as ADCs with anti-PD-1 or PARP inhibitor therapies, have also shown enhanced tumor regression in preclinical models and are the subject of several ongoing clinical trials. This review highlights the current landscape of B7-H4-targeted agents, their progress in clinical trials, and the potential for combination approaches to improve outcomes in B7-H4-expressing cancers.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"8 2","pages":"153-160"},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975504","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":"Antibody-Drug Conjugate-Induced Pneumonitis: A Growing Threat.","authors":"Kathy L Chan, Saadia A Faiz, Ajay Sheshadri","doi":"10.36401/JIPO-25-X1","DOIUrl":"https://doi.org/10.36401/JIPO-25-X1","url":null,"abstract":"","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"8 2","pages":"141-142"},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996137","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":"Lefitolimod in Combination with Ipilimumab in Patients with Advanced Solid Tumors: A Phase I Trial.","authors":"Mirella Nardo, Mohamed A Gouda, Matthew J Reilley, Amadeo B Biter, Joann Lim, Stacie A Bean, Ly M Nguyen, Priya R Bhosale, Casey R Ager, Coline A Couillault, Sarina A Piha-Paul, Siqing Fu, Apostolia M Tsimberidou, Timothy A Yap, Aung Naing, Jordi Rodon, Vivek Subbiah, Daniel D Karp, Michael A Curran, David S Hong","doi":"10.36401/JIPO-24-17","DOIUrl":"10.36401/JIPO-24-17","url":null,"abstract":"<p><strong>Introduction: </strong>TLR9 agonists are immunomodulators that have been of interest for combined use with cancer immunotherapy. TLR9 agonists, such as lefitolimod (MGN1703), significantly increased Th1 response in preclinical models and have demonstrated efficacy in early clinical trials. This trial assessed the safety and preliminary efficacy of the combination of lefitolimod and ipilimumab in patients with advanced solid tumors.</p><p><strong>Methods: </strong>This was a single-center, open-label, investigator-initiated phase I trial conducted at The University of Texas MD Anderson Cancer Center. Patients received leftolimod either subcutaneously (at escalating doses of 15-120 mg) or intratumorally (at the maximum feasible dose) in combination with ipilimumab (3 mg/kg). Paired biopsy samples were collected before the start of treatment and after two treatment cycles and analyzed by flow cytometry.</p><p><strong>Results: </strong>We enrolled a total of 28 patients in this study with a median age of 56 years (range 19-75) in the escalation cohort and 60 years (range 34 -92) in the expansion cohort. The median number of prior lines of therapy was 4 (range 0-12). Eleven patients had at least one treatment-related adverse event (TRAE). The most common TRAEs were skin rash (<i>n</i> = 4, 14%), fatigue (<i>n</i> = 3, 11%), and pruritis (<i>n</i> = 2, 7%). No grade 4 or 5 AEs occurred, and no patients required dose reduction or treatment discontinuation due to AEs. The maximum tolerated dose (MTD) was not reached in this study. Of 28 patients, 21 patients had response-evaluable disease. No patients had a complete or partial response; 8 and 13 patients had stable and progressive disease as the best response, respectively. Paired biopsy samples were obtained from five patients. Increases in intratumoral CD8 T-cell frequency, memory CD8 phenotype (CD45RO⁺), and proliferation (Ki67⁺) in four of five patients suggested that the combination of lefitolimod and ipilimumab led to proinflammatory immune conditioning of the tumor microenvironment.</p><p><strong>Conclusions: </strong>The combination of lefitolimod (administered subcutaneously or intratumorally) and ipilimumab was safe and well tolerated but demonstrated modest antitumor activity in patients with advanced cancers. <b>ClinicalTrials.gov ID: NCT02668770</b>.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"8 2","pages":"89-98"},"PeriodicalIF":3.2,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11824599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433022","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":"Selinexor (KPT-330) in Combination with Immune Checkpoint Inhibition in Uveal Melanoma: A Phase 1B Trial.","authors":"Mohamed A Gouda, Abdulrazzak Zarifa, Yali Yang, Bettzy Stephen, Serdar A Gurses, Ashabari Sprenger, Yanyan Tian, Mohamed H Derbala, Isabella Glitza Oliva, Funda Meric-Bernstam, Sapna P Patel","doi":"10.36401/JIPO-24-10","DOIUrl":"10.36401/JIPO-24-10","url":null,"abstract":"<p><strong>Introduction: </strong>Uveal melanoma remains a disease with aggressive behavior and poor prognosis despite advances in clinical management. Because monotherapy with immune checkpoint inhibitors has led to limited improvement in response rates, combination with other agents that act on the biological basis of oncogenesis has been proposed as a possible therapeutic strategy.</p><p><strong>Methods: </strong>We designed a phase 1b trial to test the safety and tolerability of selinexor in combination with immune checkpoint inhibitors in patients with advanced uveal melanoma. Patients received selinexor 60 mg PO twice weekly with standard of care, commercially available immune checkpoint inhibitor of the investigator's choice. In one patient receiving nivolumab and ipilimumab as the immunotherapy backbone, selinexor 60 mg PO was given once weekly.</p><p><strong>Results: </strong>We included 10 patients with uveal melanoma who received treatment with either selinexor plus pembrolizumab (<i>n</i> = 9) or selinexor plus nivolumab and ipilimumab (<i>n</i> = 1). The most common adverse events of any grade were neutropenia, thrombocytopenia, leukopenia, and anemia. Additional common nonhematological toxicities included hyponatremia, nausea, and vomiting. Dose reductions were required in six patients (60%). Among nine patients with evaluable disease, eight had stable disease as the best response. The median progression-free and overall survival were 6 months (95% CI: 4, not reached and 17 months (95% CI: 7, not reached), respectively.</p><p><strong>Conclusion: </strong>The combination of selinexor and immunotherapy was safe and showed a side effect profile consistent with previous reports. Clinical benefit was achieved in most patients and should be validated in larger phase 2 trials. ClinicalTrials.gov ID: NCT02419495.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"8 1","pages":"82-88"},"PeriodicalIF":3.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006561","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":"Safety and Efficacy of Toripalimab in Patients with Cholangiocarcinoma: An Open-Label, Phase 1 Study.","authors":"Aung Naing, Amit Mahipal, Milind Javle, Judy Wang, Todd M Bauer, David L Bajor, Anthony D Elias, Anthony Shields, Elizabeth Davis, Sant Chawla, Howard Safran, John D Powderly, Gina D'Amato, Christian F Meyer, Xiongwen Tang, Sheng Yao, Patricia Keegan","doi":"10.36401/JIPO-24-8","DOIUrl":"10.36401/JIPO-24-8","url":null,"abstract":"<p><strong>Introduction: </strong>This was the first phase 1 study conducted in the United States. It consisted of dose-escalation (part A) and multiple indication-specific cohort expansion (part B), investigating the safety and preliminary efficacy of toripalimab (anti-programmed cell death-1 inhibitor) in patients with advanced malignancies.</p><p><strong>Methods: </strong>Patients with advanced malignancies that progressed after treatment with at least one prior line of standard systemic therapy, including the patients with advanced/recurrent cholangiocarcinoma (CCA), received toripalimab 240 mg every 3 weeks in part B. The primary endpoint was safety assessment. Efficacy endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) as assessed by the investigators according to Response Evaluation Criteria in Solid Tumors (version 1.1) and overall survival (OS).</p><p><strong>Results: </strong>In part B, 166 patients, including the 42 patients with CCA, were enrolled and received toripalimab. Among the 166 patients, treatment-emergent adverse events (TEAEs) of any grade occurred in 158 (95.2%) patients, and 97 (58.4%) patients experienced TEAEs of Grade 3 or greater. The most common TEAE was fatigue (42.2%). Seven (4.2%) patients experienced TEAEs with a fatal outcome, none of which were identified by investigators as related to toripalimab. Investigator-assessed immune-related adverse events (irAE) of Grade 3 or higher occurred in 7 (4.2%) patients. In the CCA cohort, with the median follow-up of 4.4 months, the ORR and DCR were 4.8% (95% CI: 0.58, 16.16) and 40.5% (95% CI: 25.63, 56.72), respectively; median DoR was 7.8 (range 4.4+ to 7.8) months; median PFS was 2.1 (95% CI: 1.91, 3.88) months; median OS was not estimable.</p><p><strong>Conclusions: </strong>Toripalimab had manageable side effects in patients with refractory cholangiocarcinoma and exhibited preliminary evidence of anti-tumor activity. However, further information regarding biomarkers is needed. <b>ClinicalTrials.gov ID: NCT03474640</b>.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"8 1","pages":"71-81"},"PeriodicalIF":3.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006559","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":"Successful Targeting of Somatic <i>VHL</i> Alterations With Belzutifan in Two Cases.","authors":"Bicky Thapa, Aditya Shreenivas, Kathryn Bylow, Hui-Zi Chen, Ben George, Razelle Kurzrock","doi":"10.36401/JIPO-24-13","DOIUrl":"https://doi.org/10.36401/JIPO-24-13","url":null,"abstract":"<p><p>Clear cell renal cell carcinoma (RCC) is commonly associated with alterations in the <i>VHL</i> tumor suppressor gene, resulting in upregulation of hypoxia-inducible factor pathways. Immune checkpoint inhibitors and vascular endothelial growth factor inhibitors are the mainstays of systemic treatment for metastatic RCC; however, most patients encounter disease progression after the initial response. The phase 3 clinical trial LITESPARK-005-belzutifan (HIF-2α inhibitor) demonstrated improvement in progression-free survival compared with everolimus in heavily pretreated patients unselected for somatic/germline <i>VHL</i> alterations (an objective response rate of 23% and a median time on therapy of 7.6 months in the belzutifan cohort), resulting in U.S. FDA approval for patients with advanced RCC. Herein, we present two cases of refractory metastatic RCC (including one with brain metastases) with somatic <i>VHL</i> mutations who received belzutifan after discussion in the institutional Molecular Tumor Board. Both patients had an excellent clinical response (partial remissions ongoing at >12 and >20 months). Future studies should assess the merits of biomarker selection for belzutifan treatment.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"7 4","pages":"308-313"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621982","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}