BJC reports最新文献

{"title":"Tumour measurements on imaging for clinical trial: A national picture of service provision.","authors":"Georgina Hopkinson, Jonathan Taylor, Jonathan Wadsley, Angela Darekar, Christina Messiou, Dow-Mu Koh","doi":"10.1038/s44276-025-00131-8","DOIUrl":"10.1038/s44276-025-00131-8","url":null,"abstract":"<p><strong>Background: </strong>Radiological response evaluation metrics such as RECIST 1.1 inform critical endpoints in oncology trials. The UK was the 6th highest recruiter into oncology trials worldwide between 1999 and 2022, with almost 9000 oncology trials registered during the same period. However, the provision of tumour measurements for oncology trials is often ad hoc and patchy across the NHS. The aim of this work was to understand the barriers to providing an effective imaging tumour measurement service, gain insight into service delivery models and consider the successes and challenges from the perspective of both service providers and end users.</p><p><strong>Methods: </strong>An electronic survey was distributed to those who provide tumour measurement response review for clinical trials (service providers) and those that request and use such measurements in trial activities (service users).</p><p><strong>Results: </strong>Responses from 35 sites demonstrated substantial variation in service provision across the UK. Despite workforce pressures, service is largely delivered through radiologists with a minority utilising radiographer role extension. Only 20% of the service providers had dedicated training and 29% received robust financial reimbursement.</p><p><strong>Discussion: </strong>Service variation is likely a consequence of limited training, education and infrastructure to support robust service, compounded by increasing radiology workload and workforce pressures.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"19"},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733691","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":"Germline copy number variants in RUNX1: An updated case report and a decade-old red herring.","authors":"Natalie T Deuitch, Amra Kajdic, Erica Bresciani, Marshall S Horwitz, Hamish S Scott, Katie Craft, Shawn Chong, David J Young, Lucy A Godley, Paul P Liu","doi":"10.1038/s44276-024-00117-y","DOIUrl":"10.1038/s44276-024-00117-y","url":null,"abstract":"<p><p>Pathogenic/likely pathogenic (P/LP) germline variants in RUNX1 cause familial platelet disorder with associated myeloid malignancies (FPDMM), also known as RUNX1-Familial Platelet Disorder (RUNX1-FPD, or FPD), a condition characterized by qualitative and quantitative platelet defects and predisposition to hematopoietic malignancies. Here, we present follow up to a case of a woman with acute myeloid leukemia and lifelong thrombocytopenia which had previously been attributed to presumptive pathogenic (P) GATA2 missense variants. However, re-evaluation with updated molecular technology sensitive for detection of copy number variants (CNVs) led to the identification of a P deletion of exons 5-6 in RUNX1, which had been undetected when examined at first presentation. This case highlights the importance of comprehensive molecular evaluation and careful variant interpretation, especially regarding CNVs.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"18"},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733667","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":"A phase Ia study of the MEK1/2 inhibitor PD-0325901 with the c-MET inhibitor crizotinib in patients with advanced solid cancers.","authors":"Peter Gallagher, Christian Rolfo, Elena Elez, Julien Taieb, Jennifer Houlden, Linda Collins, Corran Roberts, Thierry André, Mark Lawler, Federica Di Nicolantonio, Margaret Grayson, Ruth Boyd, Vlad Popovici, Alberto Bardelli, Robbie Carson, Hajrah Khawaja, Pierre Laurent-Puig, Manuel Salto-Tellez, Bryan T Hennessy, Tim S Maughan, Josep Tabernero, Richard Adams, Robert Jones, Marc Peeters, Mark R Middleton, Richard H Wilson, Sandra Van Schaeybroeck","doi":"10.1038/s44276-025-00133-6","DOIUrl":"10.1038/s44276-025-00133-6","url":null,"abstract":"<p><strong>Background: </strong>Single-agent MEK1/2 inhibition has been disappointing in clinical trials targeting RAS mutant (MT) cancers, probably due to upstream receptor activation, resulting in resistance. We previously found that dual c-MET/MEK1/2 inhibition attenuated RASMT colorectal cancer (CRC) xenograft growth. In this study, we assessed safety of MEK1/2 inhibitor PD-0325901 with c-MET inhibitor crizotinib and determined the optimal biological doses for subsequent clinical trials.</p><p><strong>Methods: </strong>In this dose-escalation phase I trial, patients with advanced solid tumours received PD-0325901 with crizotinib, using a rolling-6 design to determine the maximum tolerable dose (MTD) and safety/tolerability. Blood samples for pharmacokinetics and skin biopsies were collected.</p><p><strong>Results: </strong>Twenty-five patients were recruited in 4 cohorts up to doses of crizotinib 200 mg B.D continuously with PD-0325901 8 mg B.D, days 1-21 every 28 days. One in six patients exhibited a dose-limiting toxicity at this dose level. Drug-related adverse events were in keeping with single-agent toxicity profiles. The best clinical response was stable disease in seven patients (29%).</p><p><strong>Conclusions: </strong>PD-0325901/crizotinib can be given together at pharmacologically-active doses. The MTD for PD-0325901/crizotinib was 8 mg B.D (days 1-21) and 200 mg B.D continuously in a 28-days cycle. The combination was further explored with an alternate MEK1/2 inhibitor in RASMT CRC patients.</p><p><strong>Eudract-number: </strong>2014-000463-40.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"17"},"PeriodicalIF":0.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723085","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":"A novel multigene panel (Sig27) robustly predicts poor prognosis of renal cell carcinoma via high-level associations with immunosuppressive features.","authors":"Ying Dong, Bobby Shayegan, Yingying Su, Sandra Vega Neira, Damu Tang","doi":"10.1038/s44276-025-00128-3","DOIUrl":"10.1038/s44276-025-00128-3","url":null,"abstract":"<p><strong>Background: </strong>We investigated a 27-gene panel (Sig27), derived from prostate cancer, for risk stratification of RCC (clear cell RCC/ccRCC, papillary RCC/pRCC, and chromophobe RCC/chRCC).</p><p><strong>Methods: </strong>Sig27 gene expressions were examined in 960 RCC and 201 kidney tissues. Sig27 was evaluated for predicting overall survival (OS), association with immune checkpoints (IC), regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSC), and tumor-associated macrophages (TAM) in RCC.</p><p><strong>Results: </strong>Sig27 robustly predicts OS of ccRCC, pRCC, and chRCC. Sig27 stratifies high-risk ccRCCs: median survival month (MSM) 19.3 and 80.4% of deaths and high-risk pRCCs (MSM 19.6 and 58.6% of death) compared to low-risk ccRCCs (2.9% of death) and pRCCs (2.7% of fatality). Sig27 contains several novel genes related to the RCC immunosuppressive features. FPR3, NOD2, MCTP1, LAMP3, TFEC, and FAM65B are highly correlated with MDSC, Treg, TAM and multiple (≥12) ICs in RCCs. FPR3 and NOD2 are pattern recognition receptors and initiate proinflammatory responses via sensing pathogen-associated molecular patterns and damage-associated molecular patterns; their upregulations may contribute to chronic inflammation in RCC. The Sig27 metagene is expressed in ccRCC-associated immune cells: exhausted CD8T cells, TAM, Treg, and others.</p><p><strong>Conclusions: </strong>Sig27 is a novel and effective pan-RCC biomarker with high-level associations with RCC immunosuppressive features.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"16"},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652957","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":"Epidemiology of multimorbidity in childhood cancer survivors: a matched cohort study of inpatient hospitalisations in Western Australia.","authors":"Tasnim Abdalla, Jeneva L Ohan, Angela Ives, Daniel White, Catherine S Choong, Max Bulsara, Jason D Pole","doi":"10.1038/s44276-024-00114-1","DOIUrl":"10.1038/s44276-024-00114-1","url":null,"abstract":"<p><strong>Background: </strong>Childhood cancer survivors (CCS) experience an elevated burden of health complications, underscoring the importance of understanding the patterns of multimorbidity to guide the management of survivors with complex medical needs.</p><p><strong>Methods: </strong>We examined the patterns of hospitalisations with multimorbidity in 5-year CCS (n = 2938) and age- and sex-matched non-cancer comparisons (n = 24,792) using statewide records of inpatient admissions in Western Australia from 1987 to 2019.</p><p><strong>Results: </strong>Multimorbidity rates were higher for CCS (10.6, 95%CI 10.2-10.9) than for non-cancer comparisons (3.2, 95%CI 3.2-3.3). CCS exhibited a significantly higher adjusted hazard ratio of multimorbidity, particularly when admitted for neoplasms (14.6, 95%CI 11.2-19.1), as well as blood (7.3, 95%CI 4.9-10.7), neurological and sensory (5.2, 95%CI 4.2-6.6), and cardiovascular (3.6, 95%CI 2.6-4.8) diseases. By the age of 55 years, chronic multimorbidity was more prevalent in survivors than in comparisons (14.5% vs. 5.3%). Psychiatric disorders were common comorbidities, particularly in those admitted for neurological and sensory (71.1%), endocrine (61.5%), and digestive (59.3%) diseases. Multimorbidity during hospitalisation increased the length of hospital stay (p < 0.05). Key condition clusters included (1) psychoactive substance  dependence, alcohol misuse, and other mental disorders; (2) hypertension, diabetes, kidney disease, and musculoskeletal diseases; (3) epilepsy, hypothyroidism, and other liver diseases; and (4) hypertension, kidney disease, and other liver diseases.</p><p><strong>Conclusions: </strong>These findings suggest that exposure to cancer in childhood elevates the risk of multimorbidity. The reconfiguration of healthcare delivery to enhance personalised care and clinical integration is essential for effectively managing multimorbidity in this population.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627069","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":"Predictive biomarkers for the efficacy of PARP inhibitors in ovarian cancer: an updated systematic review.","authors":"Ying-Wen Wang, Isaac Allen, Gabriel Funingana, Marc Tischkowitz, Yvonne Walburga Joko-Fru","doi":"10.1038/s44276-025-00122-9","DOIUrl":"10.1038/s44276-025-00122-9","url":null,"abstract":"<p><strong>Background: </strong>PARP inhibitors are effective in treating ovarian cancer, especially for BRCA1/2 pathogenic variant carriers and those with HRD (homologous recombination deficiency). Concerns over toxicity and costs have led to the search for predictive biomarkers. We present an updated systematic review, expanding on a previous ESMO review on PARP inhibitor biomarkers.</p><p><strong>Methods: </strong>Following ESMO's 2020 review protocol, we extended our search to March 31, 2023, including PubMed and clinical trial data. We also reviewed the reference lists of review articles. We conducted a meta-analysis using a random-effects model to evaluate hazard ratios and assess the predictive potential of biomarkers and the effectiveness of PARP inhibitors in survival.</p><p><strong>Results: </strong>We found 375 articles, 103 of which were included after screening (62 primary research, 41 reviews). HRD remained the primary biomarker (95%), particularly BRCA1/2 variants (77%). In the non-HRD category, six articles (10%) introduced innovative biomarkers, including ADP-ribosylation, HOXA9 promoter methylation, patient-derived organoids, KELIM, and SLFN11.</p><p><strong>Discussion: </strong>Prospective assessment of real-time homologous recombination repair via nuclear RAD51 levels shows promise but needs validation. Emerging biomarkers like ADP-ribosylation, HOXA9 promoter methylation, patient-derived organoids, KELIM, and SLFN11 offer potential but require large-scale validation.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607742","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":"Health inequalities in hepatocellular carcinoma surveillance, diagnosis, treatment, and survival in the United Kingdom: a scoping review.","authors":"Christopher Mysko, Stephanie Landi, Huw Purssell, A Joy Allen, Martin Prince, Gary Lindsay, Steven Rodrigues, Jenny Irvine, Oliver Street, Deepankar Gahloth, Sara MacLennan, Karen Piper Hanley, Neil Hanley, Varinder Singh Athwal","doi":"10.1038/s44276-025-00126-5","DOIUrl":"10.1038/s44276-025-00126-5","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) remains a deadly cancer in the UK despite advancements in curative therapies. Societal conditions and health inequalities influence the development of chronic liver disease and outcomes from complications including HCC. Scoping this emergent evidence-base is required to inform research and solutions for the NHS.</p><p><strong>Methods: </strong>A PRISMA scoping review was performed up to September 2023. Articles exploring health inequalities in HCC involving the UK population were included.</p><p><strong>Results: </strong>This review has characterised axes of health inequality and their impact across the HCC care continuum in the UK. Studies predominantly employed a cohort design or population-based analyses, with meta-analyses of surveillance utilisation including only a single UK study. These methodologies provided an appropriate lens to understand longitudinal trends and identify disadvantaged groups. However, important evidence gaps remain, including exploration of patient perspectives, intersectional analyses, and statistical measures of socioeconomic inequity in HCC.</p><p><strong>Conclusions: </strong>HCC is a rapidly growing cause of cancer mortality and disproportionally affects underserved groups, presenting a major public health concern. Further research is required to innovate and evaluate surveillance and management pathways to reduce systemic inequities. Direction is needed at the national level to improve prevention, early diagnosis and access to curative treatment.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143545320","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":"Deep-learning enabled combined measurement of tumour cell density and tumour infiltrating lymphocyte density as a prognostic biomarker in colorectal cancer.","authors":"Alice C Westwood, Benjamin I Wilson, Jon Laye, Heike I Grabsch, Wolfram Mueller, Derek R Magee, Phillip Quirke, Nicholas P West","doi":"10.1038/s44276-025-00123-8","DOIUrl":"10.1038/s44276-025-00123-8","url":null,"abstract":"<p><strong>Background: </strong>Within the colorectal cancer (CRC) tumour microenvironment, tumour infiltrating lymphocytes (TILs) and tumour cell density (TCD) are recognised prognostic markers. Measurement of TILs and TCD using deep-learning (DL) on haematoxylin and eosin (HE) whole slide images (WSIs) could aid management.</p><p><strong>Methods: </strong>HE WSIs from the primary tumours of 127 CRC patients were included. DL was used to quantify TILs across different regions of the tumour and TCD at the luminal surface. The relationship between TILs, TCD, and cancer-specific survival was analysed.</p><p><strong>Results: </strong>Median TIL density was higher at the invasive margin than the luminal surface (963 vs 795 TILs/mm², P = 0.010). TILs and TCD were independently prognostic in multivariate analyses (HR 4.28, 95% CI 1.87-11.71, P = 0.004; HR 2.72, 95% CI 1.19-6.17, P = 0.017, respectively). Patients with both low TCD and low TILs had the poorest survival (HR 10.0, 95% CI 2.51-39.78, P = 0.001), when compared to those with a high TCD and TILs score.</p><p><strong>Conclusions: </strong>DL derived TIL and TCD score were independently prognostic in CRC. Patients with low TILs and TCD are at the highest risk of cancer-specific death. DL quantification of TILs and TCD could be used in combination alongside other validated prognostic biomarkers in routine clinical practice.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143545317","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":"Breaking barriers: we need a multidisciplinary approach to tackle cancer drug resistance.","authors":"James Ingham, Jia-Ling Ruan, Matthew A Coelho","doi":"10.1038/s44276-025-00129-2","DOIUrl":"10.1038/s44276-025-00129-2","url":null,"abstract":"<p><p>Most cancer-related deaths result from drug-resistant disease(1,2). However, cancer drug resistance is not a primary focus in drug development. Effectively mitigating and treating drug-resistant cancer will require advancements in multiple fields, including early detection, drug discovery, and our fundamental understanding of cancer biology. Therefore, successfully tackling drug resistance requires an increasingly multidisciplinary approach. A recent workshop on cancer drug resistance, jointly organised by Cancer Research UK, the Rosetrees Trust, and the UKRI-funded Physics of Life Network, brought together experts in cell biology, physical sciences, computational biology, drug discovery, and clinicians to focus on these key challenges and devise interdisciplinary approaches to address them. In this perspective, we review the outcomes of the workshop and highlight unanswered research questions. We outline the emerging hallmarks of drug resistance and discuss lessons from the COVID-19 pandemic and antimicrobial resistance that could help accelerate information sharing and timely adoption of research discoveries into the clinic. We envisage that initiatives that drive greater interdisciplinarity will yield rich dividends in developing new ways to better detect, monitor, and treat drug resistance, thereby improving treatment outcomes for cancer patients.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525982","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":"CITRINO: phase 1 dose escalation study of anti-LAG-3 antibody encelimab alone or in combination with anti-PD-1 dostarlimab in patients with advanced/metastatic solid tumours.","authors":"J Randolph Hecht, Jean-Marie Michot, David Bajor, Amita Patnaik, Ki Y Chung, Judy Wang, Gerald Falchook, James M Cleary, Richard Kim, Anuradha Krishnamurthy, Omkar Marathe, Hagop Youssoufian, Catherine Ellis, Angela Waszak, Srimoyee Ghosh, Hailei Zhang, Kaitlin Yablonski, Shruti D Shah, Ivan Diaz-Padilla, Susanna Ulahannan","doi":"10.1038/s44276-024-00118-x","DOIUrl":"10.1038/s44276-024-00118-x","url":null,"abstract":"<p><strong>Background: </strong>Dual programmed cell death protein (ligand)-1 (PD-[L]1) and lymphocyte-activation gene-3 (LAG-3) blockade has demonstrated improved anti-tumour response in some advanced solid tumours. CITRINO, a two-part, Phase 1 dose-escalation study, evaluated encelimab (TSR-033; novel anti-LAG-3) monotherapy and in combination in patients with advanced/metastatic solid tumours.</p><p><strong>Methods: </strong>Part 1 (P1) involved dose escalation (20-720 mg Q2W) of encelimab as monotherapy (P1A/B) and with dostarlimab (500 mg Q3W) in patients with previously treated advanced/metastatic solid tumours (P1C). P2 involved cohort expansion in patients with anti-PD-(L)1-naïve microsatellite stable advanced/metastatic colorectal cancer with recommended phase 2 dose (RP2D) of encelimab with dostarlimab as third/fourth-line therapy (P2A), or with dostarlimab, bevacizumab and mFOLFOX6/FOLFIRI as second-line therapy (P2B). Objectives included RP2D, safety/tolerability, efficacy, pharmacokinetics/pharmacodynamics, and exploratory biomarkers.</p><p><strong>Results: </strong>Maximum tolerated encelimab dose was not reached; 720 mg Q2W was used for P2 plus dostarlimab 1000 mg Q6W. One dose-limiting toxicity occurred (Grade 2 myasthenia gravis; P1A). No clinical responses were observed in P1; 1 (3%) and 4 (17%) patients achieved partial response in P2A and 2B, respectively.</p><p><strong>Conclusions: </strong>Encelimab has a manageable safety profile as a monotherapy and in tested combinations; however, anti-tumour activity was limited.</p><p><strong>Clinical trial registration: </strong>NCT03250832.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525983","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}