Oncologist最新文献

{"title":"Effects of magnesium concentration on the regulation of nutrition and inflammation in nutritional support for cancer patients.","authors":"Xuelong Li, Wenjing Gong, Xiaoyan Yao, Yuanyuan Gao, Jing Wang","doi":"10.1093/oncolo/oyaf211","DOIUrl":"https://doi.org/10.1093/oncolo/oyaf211","url":null,"abstract":"<p><strong>Objectives: </strong>Magnesium plays a crucial role in metabolic homeostasis and energy balance. This study aims to evaluate the effect of magnesium in regulating nutritional status and inflammatory responses in nutritional support.</p><p><strong>Methods: </strong>A survey of 86 lung cancer patients was conducted. The oral nutrition supplement group was given an oral nutritional solution that was magnesium rich on the basis of the routine diet in the hospital, while a routine hospital diet was given to the control group. Changes in magnesium concentration, nutritional status and inflammatory indicators were compared between groups.</p><p><strong>Results: </strong>There was no significant difference in the indicators on 1st day and 10th day compared to the control group (P > 0.05). However, the levels of Mg, ALB, PA, Hb and TLC in the oral nutrition supplement group were significantly increased and the levels of TNF-α, IL-6 and CRP were significantly reduced on the 21st day (P < 0.05).</p><p><strong>Conclusions: </strong>Changes in magnesium concentration can improve nutritional status and inflammatory response. The synergistic effect of magnesium concentration and nutritional support may open a new avenue for the prevention and treatment of cancer patients.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144612348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Response to Novel Combination of Trastuzumab Deruxtecan and Abiraterone in HER2-Expressing Metastatic Castration-Resistant Prostate Cancer.","authors":"Rithika Rajendran, Coen J Lap, Siddharth Madapoosi, Angela Heiraty, Fayez Estephan, Winnie Hahn, Aarati Poudel, Victor E Nava, Ramesh Subrahmanyam, Maneesh Jain","doi":"10.1093/oncolo/oyaf207","DOIUrl":"https://doi.org/10.1093/oncolo/oyaf207","url":null,"abstract":"<p><p>Human Epidermal Growth Factor Receptor 2 (HER2) is expressed in approximately 60-70% of patients with metastatic castration-resistant prostate cancer (mCRPC) and may contribute to androgen resistance. This case report describes a patient with HER2-expressing mCRPC who progressed on multiple lines of therapy and subsequently had a significant response to combination treatment with the HER2-targeting antibody-drug-conjugate (ADC) trastuzumab deruxtecan (T-DXd) and re-challenge of abiraterone, despite having progressed on this prior. Unlike other HER2-expressing malignancies, HER2 overexpression in prostate cancer (PCa) occurs in the absence of HER2 mutations and amplifications and, as such, is not detected by next-generation sequencing. Therefore, identifying patients with mCRPC who could benefit from T-DXd necessitates HER2 testing by immunohistochemistry (IHC), a practice not routinely performed. As a result, T-DXd remains underutilized in patients with mCRPC, despite a tumor-agnostic approval for patients with advanced HER2-expressing (IHC 3+) solid tumors. This case highlights the potential of combining T-DXd with androgen receptor pathway inhibitors to overcome treatment resistance and underscores the importance of routine HER2 IHC testing in patients with advanced PCa.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dupilumab for Bullous Pemphigoid Related to Immune Checkpoint Inhibitors: A Retrospective Case Series.","authors":"Ian Nykaza, Andrea Moy, Stephen W Dusza, Alison Moskowitz, Gopa Iyer, Afsheen Iqbal, Robert Motzer, David H Ilson, Roisin E O'Cearbhaill, Rashek Kazi, Jennifer Defazio, Allison Gordon, Alina Markova","doi":"10.1093/oncolo/oyaf208","DOIUrl":"https://doi.org/10.1093/oncolo/oyaf208","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but are associated with treatment-limiting immune-related cutaneous adverse events (irCAEs). ICI-related Bullous pemphigoid (irBP), a severe, blistering irCAE occurs in 0.3-1.5% of patients receiving ICI therapy. While systemic steroids can be effective, they are associated with significant toxicity and may mitigate immunotherapy antitumor efficacy. Consequently, steroid-sparing therapies are needed. Dupilumab, an IL-4 and IL-13 receptor antagonist, has demonstrated efficacy in non-ICI-related BP and appears promising for managing irBP.</p><p><strong>Methods: </strong>We conducted a retrospective review of patients treated with dupilumab for irBP from April 2020 to April 2024. Clinical data, outcomes, and adverse events were assessed. irBP response was categorized as complete response (CR), partial response (PR), or no response (NR).</p><p><strong>Results: </strong>17 patients (59% male, 82% non-Hispanic White; mean age 72.7 years) developed irBP while receiving PD-1/PDL-1 inhibitors. Sixteen patients (94%) received dupilumab for active irBP and one (6%) for prevention of recurrence. Dupilumab achieved CR of irBP for 12 patients (75%) and PR for two (12%) patients with active irBP. Ten (62%) achieved CR with dupilumab systemic monotherapy. Median time to first response was 19.5 days (range = 3-50). Most patients with CR (58%) failed prior oral corticosteroid therapy. The patient treated prophylactically experienced no irBP recurrence. Dupilumab was well-tolerated, with no adverse events.</p><p><strong>Conclusions: </strong>Dupilumab is a promising steroid-sparing option for irBP, achieving initial response in under 20 days for most cases. Dupilumab is a valuable tool to manage this challenging irCAE while minimizing risk related to systemic steroid treatment.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sporadic medullary thyroid carcinoma with a rare RET transmembrane domain mutation (A641R) that responds to selpercatinib.","authors":"Naoki Fukuda, Kazuhisa Toda, Tomohiro Chiba, Ippei Fukada, Seiichi Mori, Akiko Tonooka, Erisa Toda, Jumpei Yoshida, Xiaofei Wang, Ryosuke Oki, Takehiro Nakao, Tetsuya Urasaki, Kenji Nakano, Makiko Ono, Junichi Tomomatsu, Kengo Takeuchi, Shunji Takahashi, Yuji Miura","doi":"10.1093/oncolo/oyaf209","DOIUrl":"https://doi.org/10.1093/oncolo/oyaf209","url":null,"abstract":"<p><p>Medullary thyroid carcinoma is a rare thyroid malignancy derived from parafollicular C cells that is frequently driven by activating mutations in the REarranged during Transfection (RET) proto-oncogene. While most actionable RET mutations are located in the extracellular cysteine-rich or intracellular tyrosine kinase domains, mutations in the transmembrane domain are exceedingly rare and their oncogenic significance remains unclear. We report a case of a 59-year-old male with sporadic medullary thyroid carcinoma harboring a rare RET A641R mutation in the transmembrane domain. The patient experienced multiple locoregional recurrences after four surgical resections. While the companion diagnostic test did not identify RET mutations, comprehensive genomic profiling using a next-generation sequencing panel revealed the RET A641R mutation. Following administration of selpercatinib, a selective RET inhibitor, a rapid biochemical response with decreased serum carcinoembryonic antigen and calcitonin levels was observed, and radiological assessment showed partial response. This is the first report demonstrating the clinical efficacy of selpercatinib in a patient with medullary thyroid carcinoma harboring a RET A641R mutation, supporting the oncogenic potential of this rare variant. This case also emphasizes the importance of comprehensive genomic profiling in identifying rare but actionable RET alterations that are undetectable by targeted sequencing companion diagnostic tests. Selpercatinib may represent an effective therapeutic option for patients with medullary thyroid carcinoma driven by uncommon RET mutations, including mutations in the transmembrane domain.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence and Risk of Hypertension and Proteinuria in Cancer Patients Treated with Lenvatinib: A Systematic Review and Meta-analysis.","authors":"Yuma Shibutani, Atsuko Suzuki, Takuro Imaoka, Kazuko Tajiri","doi":"10.1093/oncolo/oyaf203","DOIUrl":"https://doi.org/10.1093/oncolo/oyaf203","url":null,"abstract":"<p><strong>Background: </strong>Published data regarding the overall risks and incidence of hypertension and proteinuria associated with lenvatinib remain unclear.</p><p><strong>Methods: </strong>We performed a systematic review and meta-analysis to quantify the precise risks and incidence of lenvatinib-associated hypertension and proteinuria. We systematically searched PubMed, Cochrane Library, and Web of Science databases for studies on the incidence of hypertension and proteinuria, which were published until April 24, 2023.</p><p><strong>Results: </strong>A total of 10,443 patients were included in the 64 studies identified from the literature. The incidence of all-grade and grade ≥3 hypertension was 50% (95% confidence interval [CI]: 43-58%) and 14% (95% CI: 10-18%) for patients treated with lenvatinib. The incidence of all-grade and grade ≥3 proteinuria was 32% (95% CI: 26-38%) and 6% (95% CI: 4-7%), respectively. Compared with controls, lenvatinib significantly increased the risk of all-grade hypertension (odds ratio [OR]: 2.4, 95% CI: 1.4 - 4.1), grade ≥3 hypertension (OR: 2.7, 95% CI: 1.2 - 6.0), all-grade proteinuria (OR: 3.5, 95% CI: 1.9 - 6.6), and grade ≥3 proteinuria (OR: 2.85, 95% CI: 1.5 - 5.3). Compared to low-dose lenvatinib (≤12 mg/day), high-dose lenvatinib (≥20 mg/day) treatment significantly increased the risks of all-grade hypertension (OR: 4.7, 95% CI: 4.2 - 5.2), grade ≥3 hypertension (OR: 7.7, 95% CI: 6.8 - 8.7), all-grade proteinuria (OR: 1.8, 95% CI: 1.6 - 2.0), and grade ≥3 proteinuria (OR: 1.7, 95% CI: 1.5 - 2.1).</p><p><strong>Conclusion: </strong>Our review revealed that lenvatinib treatment increases the risks of hypertension and proteinuria, particularly with high-dose lenvatinib.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A mixed-method analysis of oncologist-patient communications about immune checkpoint inhibitors (COACH).","authors":"Wenwen Chen, Julia Majovski, Shailender Bhatia, Anissa Chan, Petros Grivas, Sylvia Lee, Sumit Shah, John A Thompson, Scott S Tykodi, Joshua R Veatch, Lidia Schapira, Evan T Hall","doi":"10.1093/oncolo/oyaf064","DOIUrl":"10.1093/oncolo/oyaf064","url":null,"abstract":"<p><strong>Background: </strong>Despite significant attention in the media and oncology community about improved outcomes associated with immune checkpoint inhibitors (ICIs), there remains a gap in our understanding of how oncologists describe ICIs to their patients. Communication around ICIs represents a challenge as some patients have durable, remarkable benefits while others experience severe toxicities. We investigated oncologist-patient communication practices by performing a mixed-methods study of in-clinic discussions about ICIs.</p><p><strong>Materials and methods: </strong>This was a mixed-method study in which in-clinic conversations between oncologists and their patients with advanced cancers about ICIs as potential treatments were audio-recorded. Patients were asked to complete a post-discussion survey. Qualitative data was derived from a general inductive thematic approach while descriptive statistics were used to analyze the survey responses.</p><p><strong>Results: </strong>We recorded and analyzed 13 in-clinic conversations involving 8 oncologists and 13 patients. Twelve patients completed the post-discussion surveys. The conversations involved sophisticated discussions of immune function, cancer and ICI mechanisms, and trade-offs between anticancer benefits and toxicities. Oncologists incorporated metaphors and probabilistic information in their explanations. In the post-discussion surveys, patients indicated a preference for detailed information about ICIs and reported that they received the right depth of information in these discussions.</p><p><strong>Conclusions: </strong>During in-clinic discussions of ICI therapy, oncologists provided detailed information about immunology and cancer, often aided by metaphors. Probabilities were commonly used to describe the likelihood of toxicities and benefits. The amount of information provided by the oncologists aligned with the patients' preference for detailed information about their cancer treatments.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":"30 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-in-human phase I open-label study of the anti-TIM-3 monoclonal antibody INCAGN02390 in patients with select advanced or metastatic solid tumors.","authors":"Martin E Gutierrez, Shou-Ching Tang, John D Powderly, Ani S Balmanoukian, Paul E Hoyle, Zhiwan Dong, Lulu Cheng, Xiaohua Gong, John E Janik, Nawel Bourayou, Omid Hamid","doi":"10.1093/oncolo/oyaf144","DOIUrl":"10.1093/oncolo/oyaf144","url":null,"abstract":"<p><strong>Background: </strong>T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3) is an immune checkpoint receptor upregulated during anti-programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) immunotherapy for cancer. TIM-3 blockade may improve the antitumor activity of PD-1/PD-L1inhibition. This phase 1 study evaluated INCAGN02390, a novel, fully human Fc-engineered antibody against TIM-3.</p><p><strong>Methods: </strong>INCAGN02390 was evaluated by dose escalation at 10-1600 mg infused in 14-day cycles (every 2 weeks [Q2W]) in pretreated patients with select advanced/metastatic immunogenic solid tumors. Objectives included evaluation of safety/tolerability and maximum tolerated dose (MTD) (primary), pharmacokinetics, preliminary antitumor activity, pharmacodynamics, and immunogenicity (secondary).</p><p><strong>Results: </strong>Forty patients were enrolled and treated with INCAGN02390; 60% had previously received ≥3 lines of systemic therapy. Forty-eight percent had received a prior immune checkpoint inhibitor (anti-PD-1/PD-L1 therapy, 43%; anti-cytotoxic T-lymphocyte associated protein-4 therapy, 23%). No dose-limiting toxicities (DLTs) were observed and MTD was not reached. Twelve patients (30%) had treatment-related adverse events (TRAEs), most commonly fatigue and pruritus (n = 3 each); 3 (8%) had grade ≥3 TRAEs. Four patients (10%) experienced sponsor-assessed irAEs. One patient (3%) achieved partial response (duration, 5.7 months) and 6 had stable disease (≥56 days in all patients, >18 months in 2 patients).</p><p><strong>Conclusions: </strong>In this heavily pretreated population, no DLTs were reported and modest efficacy was exhibited. A 400-mg Q2W dose was selected for phase II studies investigating INCAGN02390 as part of combination immunotherapies for advanced cancers.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":"30 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacovigilance study for the identification of mogamulizumab-induced immune-related adverse events using a real-world database.","authors":"Koji Miyata, Yuki Izawa-Ishizawa, Takahiro Niimura, Toshihiko Yoshioka, Mizusa Hyodo, Shuto Itokazu, Tatsumi Miyata, Fuka Aizawa, Kenta Yagi, Kei Kawada, Hirofumi Hamano, Yoshito Zamami, Mitsuhiro Goda, Keisuke Ishizawa","doi":"10.1093/oncolo/oyaf201","DOIUrl":"10.1093/oncolo/oyaf201","url":null,"abstract":"<p><strong>Background: </strong>Mogamulizumab is a humanized anti-CCR4 monoclonal antibody used for relapsed/refractory adult T-cell leukemia, cutaneous T-cell lymphoma, and/or Sézary syndrome. Reports of immune-related adverse events (irAEs) in these patients are increasing, and the association between irAEs and mogamulizumab remains to be elucidated. This study aimed to evaluate the association between mogamulizumab and immune-related adverse events (irAEs), as well as to characterize the irAEs associated with mogamulizumab using data from a large-scale spontaneous reporting system.</p><p><strong>Methods: </strong>We performed an exploratory hypothesis-generating analysis of patients from 1967 to September 2023 using VigiBase, a World Health Organization spontaneous adverse event reporting system database. We performed a disproportionality analysis and determined the reporting odds ratios and information components between the drugs of interest and each irAE.</p><p><strong>Results: </strong>Mogamulizumab was associated with some irAEs, including myocarditis, severe cutaneous adverse reactions, hepatitis, and myositis. Mogamulizumab exhibited significantly higher reporting rates of these 4 irAEs compared to the anticancer agents other than mogamulizumab. Conversely, the reporting rate of other irAEs, including endocrine autoimmune diseases induced by immune checkpoint inhibitors, was not significant in patients who received mogamulizumab.</p><p><strong>Conclusions: </strong>Mogamulizumab is associated with irAEs, including myocarditis, severe cutaneous adverse reactions, hepatitis, and myositis.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":"30 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12242157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving genetics equity: identifying women eligible for genetic care services using mammography clinics in underserved areas as screening hubs.","authors":"Darya Kizub, Rachel Bluebond, Sierra Green, Jessica Duckworth, Sreejesh Shanker, Autumn Vara, Banu Arun","doi":"10.1093/oncolo/oyaf113","DOIUrl":"10.1093/oncolo/oyaf113","url":null,"abstract":"<p><strong>Purpose: </strong>Fewer than 20% of underserved individuals undergo guideline-concordant hereditary breast and ovarian cancer (HBOC) genetic testing (GT). Our study aimed to determine the proportion of women eligible for HBOC GT using a cancer genetics risk assessment (CGRA) tool at breast cancer (BC) screening clinics in underserved communities and to describe the program's impact.</p><p><strong>Methods: </strong>Participants were women who presented for BC screening at The Rose clinics, serving low-income underserved communities in southeast Texas, and completed the CGRA. High-risk individuals received bilingual educational materials and a saliva-based GT kit. Those with a pathogenic variant (PV) or a variant of uncertain significance (VUS) received telegenetic counseling and risk reduction resources.</p><p><strong>Results: </strong>A total of 501 women completed the CGRA, with 30.1% uninsured. 150 women were identified as eligible for GT, but only 14 (9.9%) completed GT (11 negative, 2 VUS, 1 PV in NF1). GT completion was significantly associated with being White, Native American/Alaskan Native, and Ashkenazi Jewish (P < .05). Hispanic, low-income, and uninsured individuals, or those with fewer relatives with cancer, were as likely to complete GT as others.</p><p><strong>Conclusions: </strong>We successfully identified underserved women at high risk of HBOC using CGRA, but the GT completion rate was low. However, the completion rate did not differ by Hispanic ethnicity, income, or insurance status, suggesting that financial navigation by our study coordinator, support from Spanish-language staff at The Rose clinics, and the use of Spanish-language educational materials and translation may have helped overcome some barriers.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":"30 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12231590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase 1 study of zavondemstat (TACH101), a first-in-class KDM4 inhibitor, in patients with advanced solid tumors.","authors":"Apostolia M Tsimberidou, Farshid Dayyani, David Sommerhalder, Andrae L Vandross, Meredith S Pelster, Jason T Henry, Cesar A Perez, Abhijit Chakraborty, Mehmet A Baysal, Chandtip Chandhasin, Yiyun Dai, Shirley Tu, Ivan King, Frank Perabo","doi":"10.1093/oncolo/oyaf169","DOIUrl":"10.1093/oncolo/oyaf169","url":null,"abstract":"<p><strong>Background: </strong>This was a first-in-human, phase I, dose-escalation study evaluating the safety, pharmacokinetics, and preliminary efficacy of zavondemstat (TACH101), an epigenetic targeting inhibitor of KDM4 histone demethylase, in patients with heavily pre-treated advanced/metastatic cancers.</p><p><strong>Patients and methods: </strong>Patients received zavondemstat orally on a weekly schedule in 28-day cycles. Dose escalation followed a Bayesian optimal interval design and explored both intermittent and continuous dosing. The primary objectives were to assess safety, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended phase II dose (RP2D). Secondary objectives included pharmacokinetics and radiographic response per Response Evaluation Criteria in Solid Tumors, version 1.1.</p><p><strong>Results: </strong>Thirty patients were enrolled across 6 dose cohorts. MTD was not reached at the maximum dose tested. The most common treatment-related adverse events (TRAEs) were diarrhea (12%), fatigue (7%), decreased appetite (7%), nausea (7%), and hyponatremia (7%). All TRAEs were grade 1 or 2. No serious TRAEs or DLTs were reported. Of 23 response-evaluable patients, 10 (44%) achieved stable disease (SD). Two patients (9%) had SD ≥ 6 months, including a patient with castration-resistant prostate cancer and a patient with leiomyosarcoma. A third patient (leiomyosarcoma) receiving ongoing treatment with zavondemstat under compassionate use has had SD for 6+ months. Zavondemstat demonstrated a dose-proportional exposure profile with a half-life of about 1.5 hours. There was no to minimal drug accumulation observed.</p><p><strong>Conclusions: </strong>Zavondemstat was very well tolerated and showed encouraging preliminary clinical benefit in heavily pretreated patients with advanced cancer. Continued evaluation of zavondemstat is warranted.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12236304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}