Targeted Oncology最新文献

{"title":"From Sequencing to Survival: The Growing Role of Precision Medicine in Paediatric Oncology.","authors":"Sarah M Trinder, David S Ziegler, Loretta M S Lau","doi":"10.1007/s11523-025-01178-w","DOIUrl":"https://doi.org/10.1007/s11523-025-01178-w","url":null,"abstract":"<p><p>The advent of comprehensive genomic sequencing has catalysed the emergence of paediatric precision medicine platforms globally. These have established the feasibility of profiling tumours at scale, enhancing our understanding of the genetic landscape of paediatric tumours and enabling identification of driver mutations and actionable targets. In turn, this has created the opportunity for development of novel precision-guided therapies (PGT). This commentary synthesizes evidence from major collaborative trials with a focus on outcome reporting, particularly in the relapsed/refractory and high-risk patient cohorts. Patients receiving PGT in these cohorts demonstrate meaningful responses and survival benefit, particularly when treatment is based on high-level clinical evidence and administered early in the disease course. However, challenges remain in addressing low uptake of PGT, likely hindered by substantial barriers in access and complex pharmaceutical regulatory constraints. Furthermore, heterogeneity in recommendation and outcome reporting hinders data harmonisation and generalisability of results. In addition to improving outcomes, comprehensive profiling can contribute to diagnostic refinement and identification of germline variant detection in a subset of patients. Emerging studies, conducted through national initiatives, signify the potential benefit of precision medicine for all patients with childhood cancer regardless of risk. A dynamic approach to address challenges and ensure cost-benefit is necessary to embed precision oncology as a standard of care for all children with cancer.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dermatologic Adverse Event Mitigation and Management Strategies with Amivantamab + Lazertinib Therapy for Advanced Non-Small Cell Lung Cancer: A Vodcast.","authors":"Danny Nguyen, Edgardo S Santos","doi":"10.1007/s11523-025-01163-3","DOIUrl":"10.1007/s11523-025-01163-3","url":null,"abstract":"<p><p>Targeted therapies have transformed outcomes of patients with advanced non-small cell lung cancer. Amivantamab, a bispecific antibody targeting epidermal growth factor receptor (EGFR) and MET, and lazertinib, a third-generation EGFR tyrosine kinase inhibitor, were approved in 2024 for the first-line treatment of EGFR-mutated (exon 19 deletion/exon 21 L858R substitution) locally advanced or metastatic non-small cell lung cancer. While EGFR-targeted therapies have demonstrated clinical efficacy, they are associated with on-target dermatologic adverse events (AEs). This vodcast aims to educate on strategies to mitigate and manage dermatologic AEs associated with amivantamab + lazertinib. The MARIPOSA study assessed amivantamab + lazertinib versus osimertinib in previously untreated patients with EGFR-mutated locally advanced or metastatic non-small cell lung cancer. In the same population, the COCOON study assessed the impact of enhanced versus standard dermatologic management on the incidence of grade ≥ 2 dermatologic AEs. In MARIPOSA, amivantamab + lazertinib significantly improved overall survival (median not reached vs 36.7 months) and progression-free survival (median 23.7 vs 16.6 months) versus osimertinib. The most common EGFR-associated dermatologic AEs were rash and paronychia. To address these AEs, the COCOON study evaluated enhanced dermatologic management strategies (including prophylactic oral and topical antibiotics and moisturizer) versus standard of care dermatologic management, which resulted in a two-fold reduction in grade ≥ 2 dermatologic AEs with COCOON versus standard dermatologic management. We further discuss the COCOON prophylactic regimen together with reactive and expert-recommended dermatologic management approaches. In conclusion, amivantamab + lazertinib is an effective treatment that significantly improves overall survival. While dermatologic AEs are common, effective proactive management strategies, as demonstrated in the COCOON study, can help reduce the incidence and severity of dermatologic AEs. Prioritizing education for healthcare providers and patients will facilitate timely identification and proactive and reactive management of these events, ultimately improving the treatment experience for patients undergoing therapy with amivantamab and lazertinib.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"737-742"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HER2-Positive Urothelial Carcinoma: Current Evidence on Targeted Agents and Immunotherapy-Based Combinations.","authors":"Federica Ciciriello, Gaetano Pezzicoli, Antonello Biasi, Claudia D'Addario, Francesco Salonne, Camillo Porta, Mimma Rizzo","doi":"10.1007/s11523-025-01165-1","DOIUrl":"10.1007/s11523-025-01165-1","url":null,"abstract":"<p><p>Despite the introduction of immunotherapy and antibody-drug conjugates (ADCs), 5-year survival rates for advanced urothelial cancer (UC) remain unsatisfactory. Modest results with conventional systemic treatments have prompted the need for tailored therapies that exploit actionable mutations, such as those involving the human epidermal growth factor receptor (HER)-2 proto-oncogene, which plays a key role in regulating cell growth, differentiation, and survival. HER2-positive UC accounts for 13-25% of all locally advanced/metastatic UC. HER2 overexpression in UC varies widely by tumour stage and is usually a late phenomenon associated with poorer prognosis. Given the crucial biological role of HER2 in UC and the proven activity of anti-HER2 drugs in other solid tumours (e.g. breast and gastric cancer), in this comprehensive review, we analyse clinical trials using HER2-targeting strategies in HER2-positive metastatic UC. Clinical trials of anti-HER2 monoclonal antibodies and tyrosine kinase inhibitors in UC have shown limited efficacy. On the other hand, HER2-targeted ADCs such as trastuzumab deruxtecan and disitamab vedotin have shown encouraging results. However, the most interesting data come from the combination of HER2-targeted ADCs with immunotherapy because of the synergistic action of the two drugs: HER2-directed ADCs, with their cytotoxic effect, lead to the release of cancer antigens, enhancing the anti-tumour immune response, which is boosted by the immune checkpoint inhibitor. Moreover, this combination strategy may also offer some advantages in rewiring the tumour microenvironment, favouring an anti-cancer immune response. ADC and immune checkpoint inhibitor combinations are supported by solid preclinical evidence and are emerging as novel and promising tailored therapeutic approaches for advanced UC.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"755-765"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Outcomes of Pembrolizumab in Advanced Melanoma by Age and Sex: A National Population-Based Study.","authors":"Chin Hang Yiu, Alexander M Menzies, Christine Y Lu","doi":"10.1007/s11523-025-01164-2","DOIUrl":"10.1007/s11523-025-01164-2","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors are standard treatment for advanced melanoma. Pembrolizumab (programmed cell death-1 inhibitor) monotherapy is recommended as first-line treatment. However, real-world evidence on its efficacy and safety in Australia, a region with the highest melanoma incidence, remains limited.</p><p><strong>Objective: </strong>This study aimed to assess real-world outcomes of pembrolizumab in patients with advanced melanoma in Australia.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted using national Pharmaceutical Benefits Scheme and National Death Index data via the Australian Bureau of Statistics DataLab. Patients who initiated pembrolizumab monotherapy for stage III/IV unresectable melanoma (1 January, 2017-30 June, 2022) were included. Kaplan-Meier analyses and multivariate Cox regressions were performed to assess overall survival and time to treatment discontinuation. Immune-related adverse events were inferred from corticosteroid and levothyroxine prescriptions. Subgroup analyses were performed by age (18-64, 65-84, ≥ 85 years) and sex.</p><p><strong>Results: </strong>Among 4127 patients, the median overall survival was 816 days. Mortality was higher in patients aged 65-84 years (adjusted hazards ratio 1.39, 95% confidence interval 1.24-1.56) and ≥85 years (adjusted hazards ratio 1.93, 95% confidence interval 1.69-2.21) versus 18-64 years. Median time to treatment discontinuation was 377 days, with a higher discontinuation rate in female individuals (adjusted hazards ratio 1.19, 95% confidence interval 1.09-1.29). Incident corticosteroid and levothyroxine prescriptions were observed in 19.3 and 7.6% of patients, respectively.</p><p><strong>Conclusions: </strong>Our findings align with clinical trials, demonstrating similar survival outcomes. Younger patients benefited more from pembrolizumab, while female individuals had shorter treatment durations. Further research is required to explore immune checkpoint inhibitor efficacy, safety, and treatment disparities.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"847-859"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Outcomes of T790M Mutation Testing and Sequential Osimertinib in EGFR-Positive Advanced Non-small Cell Lung Cancer: A Revisited Strategy.","authors":"Kelvin Yan, Arizah Bakhtiah, Shweta Hota, Joanne Evans, Frankie Mo","doi":"10.1007/s11523-025-01173-1","DOIUrl":"10.1007/s11523-025-01173-1","url":null,"abstract":"<p><strong>Background: </strong>Epidermal growth factor receptor (EGFR)-driven non-small cell lung cancer (eLC) is a leading cause of death. The FLAURA study showed that upfront osimertinib (U-OSI) led to better overall survival (OS) than gefitinib or erlotinib, regardless of T790M status in advanced disease. However, if sequenced optimally, sequential OSI (S-OSI) in T790M-positive patients after first- or second-generation EGFR-tyrosine kinase inhibitors (F-S-EGFR-TKI) should theoretically lead to better OS than U-OSI.</p><p><strong>Objective: </strong>To identify the best sequencing strategy in this group of patients.</p><p><strong>Patients and methods: </strong>A multicentre retrospective study was conducted on treatment-naive eLC patients who had received an F-S- EGFR-TKI between 1 January 2016 and 31 December 2020 in three tertiary NHS hospitals in the UK. Compliance to national recommendation of T790M testing was analysed. Survival outcomes of T790M testing and S-OSI were estimated with the Kaplan-Meier and Cox Proportional Hazard models.</p><p><strong>Results: </strong>In 84/122 evaluable patients, after F-S-EGFR-TKI, only 50% of the patients were offered a T790M biopsy, owing to rapid progression and reduced fitness. Of which, 59.5% of the patients tested positive and had S-OSI. Median OS for the T790M-tested cohort, regardless of positivity and S-OSI, was 54.0 months vs 8.9 months in those not tested (P = < 0.001). Median OS of S-OSI in T790M-positive patients was 64.0 months vs 34.9 months in the T790M-negative cohort (P < 0.0001). On multivariable analysis, S-OSI was associated with better OS (HR 1.841; 95% CI 1.052-3.221; P = 0.0325), whereas performance status (HR 2. 256; 95% CI 1.151-4.422, P = 0.0178), presence of baseline intracranial disease (HR 2 .022; 95% CI 1.144-3.575, P = 0. 0115), the male sex (HR 2.265; 95% CI 1.302-3.939; P = 0.0038) and non-exon 19 deletion mutations (HR 1.610; 95% CI 1.112-2.331, P = 0.0116) were associated with a higher risk of death.</p><p><strong>Conclusions: </strong>High performance status and intracranial disease should be indications for U-OSI for a higher chance of response. For fitter patients, F-S-EGFR-TKI followed by T790M biopsy +/- S-OSI appears to confer better-than-expected OS in the entire cohort in the real-world setting, regardless of T790M positivity. Given the clinical benefit and potential cost-effectiveness of this approach, S-OSI should be considered a favourable option in this group of patients, especially in resource-deprived settings.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"861-870"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Published Population Pharmacokinetic Models of Imatinib Perform Poorly on TDM Data from Pediatric Patients.","authors":"Tianwu Yang, Anna Sofie Buhl Rasmussen, Allan Weimann, Maria Thastrup, Cecilie Utke Rank, Bodil Als-Nielsen, Johan Malmros, Hilde Skuterud Wik, Olli Lohi, Ulrik Overgaard, Inga Maria Rinvoll Johannsdottir, Goda Vaitkeviciene, Kim Dalhoff, Kjeld Schmiegelow, Trine Meldgaard Lund","doi":"10.1007/s11523-025-01172-2","DOIUrl":"10.1007/s11523-025-01172-2","url":null,"abstract":"<p><strong>Background: </strong>Population pharmacokinetic models can potentially provide suggestions for an initial dose and the magnitude of dose adjustment during therapeutic drug monitoring procedures of imatinib. Several population pharmacokinetic models for imatinib have been developed over the last two decades. However, their predictive performance is still unknown when extrapolated to different populations, especially children.</p><p><strong>Objective: </strong>This study aimed to evaluate the predictive performance of these published models on an external real-world dataset containing data from both adults and children.</p><p><strong>Methods: </strong>A real-world dataset was collected, containing observations from adult and pediatric patients with Philadelphia chromosome-positive/Philadelphia chromosome-like acute lymphoblastic leukemia and chronic myeloid leukemia (N = 39) treated with imatinib. A systematic review through PubMed was conducted to identify qualified population-pharmacokinetic models for external evaluation (i.e., prediction-based, simulation-based, and Bayesian forecasting diagnostics). Standard allometric scaling was used for models that were developed based on data from adults only.</p><p><strong>Results: </strong>Fifteen published models were found for evaluation, of which only two were based on data from both children and adults. Prediction-based diagnostics showed that some models had an acceptable level of bias. The model by Shriyan et al. (with allometric scaling) performed best with a median prediction error of 1.24%. However, no models performed well on precision even when allometric scaling was used, where the lowest median absolute prediction error was 37.66% using the model by Schmidli et al. The models by Golabchifar et al. and Schmidli et al. (both with allometric scaling) performed the best of all tested models, with a median prediction error ≤ 15%, median absolute prediction error ≤ 40%, fraction of prediction error within ± 20% (F₂₀) ≥ 0.3, and within ± 30% (F₃₀) nearly 0.4. Simulation-based diagnostics showed that most of the observations outside the 90% prediction interval were from children. Bayesian forecasting showed that the model prediction could be improved using one prior sample, particularly in adults.</p><p><strong>Conclusions: </strong>Current models fail to accurately predict imatinib plasma concentrations in our real-world dataset, especially for children. Future pharmacokinetic studies should focus on developing better models for pediatric populations.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"871-886"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Precision Oncology in Rare Endocrine and Neuroendocrine Neoplasms: Experiences and Challenges of the CCCMunich^LMU Molecular Tumor Board.","authors":"Klara Dorman, Christoph J Auernhammer, Christine Spitzweg, Ralf Schmidmaier, Svenja Nölting, Matthias Kroiss, Martin Reincke, Christian Schulz, Martin Angele, Jens Werner, Christine Schmid-Tannwald, Josefine Rauch, Mathias Zacherl, Thomas Knösel, Jörg Kumbrink, Andreas Jung, Frederick Klauschen, Amanda Tufman, Danmei Zhang, Lena Weiss, Stefan Boeck, Michael von Bergwelt-Baildon, Volker Heinemann, C Benedikt Westphalen, Kathrin Heinrich","doi":"10.1007/s11523-025-01171-3","DOIUrl":"10.1007/s11523-025-01171-3","url":null,"abstract":"","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"887"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Exposure-Response Efficacy Analysis of Elranatamab (PF-06863135) in Patients with Multiple Myeloma.","authors":"Hoi-Kei Lon, Jennifer Hibma, Sibo Jiang, Sharon Sullivan, Erik Vandendries, Athanasia Skoura, Diane Wang, Mohamed Elmeliegy","doi":"10.1007/s11523-025-01168-y","DOIUrl":"10.1007/s11523-025-01168-y","url":null,"abstract":"<p><strong>Background: </strong>Elranatamab is a heterodimeric humanized full-length bispecific antibody composed of one B-cell maturation antigen (BCMA) binding arm and one cluster of differentiation 3 (CD3) binding arm. Results from the MagnetisMM-3 study indicated deep and durable responses in patients with relapsed or refractory multiple myeloma (RRMM).</p><p><strong>Objective: </strong>The current analysis was conducted to characterize the relationship between free (i.e., unbound) elranatamab exposure and objective response rate (ORR), complete response rate (CRR), progression-free survival (PFS), and duration of response (DOR), and the impact of potential covariates on these exposure-response (E-R) relationships.</p><p><strong>Patients and methods: </strong>Data from four clinical studies and a wide dosing range were used for the E-R analysis. The E-R analyses of ORR and CRR were conducted by binomial logistic regression method, whereas Kaplan-Meier (KM) curves and Cox proportional hazards (PH) model were used for PFS and DOR.</p><p><strong>Results: </strong>The analysis included data from 312 response-evaluable patients. The results suggested that higher elranatamab exposure and lower soluble BCMA (sBCMA) were associated with higher probability of achieving objective response (OR) and complete response (CR). For PFS, higher exposure was associated with longer PFS, which is driven by rapid responses or progression events within the initial treatment cycles. At later time points, a flat relationship between exposure and PFS was observed. No E-R relationship was identified for DOR.</p><p><strong>Conclusions: </strong>The current analyses support the approved initial dosing regimen of elranatamab and the dosing switch to less frequent dosing in responding patients during later treatment cycles.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov identifiers: </strong>NCT03269136, NCT04798586, NCT04649359, and NCT05014412.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"803-819"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144875334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Belantamab Mafodotin with Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma: A Comprehensive Exposure-Response Analysis of the DREAMM-8 Study.","authors":"Patrick Hanafin, Yu Liu Ho, Theodoros Papathanasiou, Giulia Fulci, Neal Sule, Brandon E Kremer, Geraldine Ferron-Brady","doi":"10.1007/s11523-025-01174-0","DOIUrl":"10.1007/s11523-025-01174-0","url":null,"abstract":"<p><strong>Background: </strong>In the phase 3 DREAMM-8 study (NCT04484623), belantamab mafodotin (anti-B-cell maturation antigen [BCMA] antibody-drug conjugate with a monomethyl auristatin F payload) with pomalidomide and dexamethasone (BPd) showed significant progression-free survival benefit in second-line or later relapsed/refractory multiple myeloma (RRMM).</p><p><strong>Objective: </strong>This exposure-response analysis explored the relationship between belantamab mafodotin cycle 1 exposure and efficacy/safety and predicted the benefit-risk profile of belantamab mafodotin at an initial dose of 1.9 versus 2.5 mg/kg using DREAMM-8 data.</p><p><strong>Patients and methods: </strong>In the BPd arm of DREAMM-8, belantamab mafodotin was dosed at 2.5 mg/kg intravenously in cycle 1, then at 1.9 mg/kg every 4 weeks from cycle 2 onward. Cycle 1 belantamab mafodotin and free payload exposures derived from population pharmacokinetic analysis were used to perform exposure-efficacy/exposure-safety analyses for probability of/time to first event. Selected covariate effects were evaluated.</p><p><strong>Results: </strong>Higher belantamab mafodotin cycle 1 exposure was associated with deeper response (higher probabilities of complete response or better [≥ CR] and minimal residual disease negativity), but not with grade ≥ 3 ocular adverse events (oAEs)/ophthalmic exam findings. Benefit-risk assessment showed that an initial belantamab mafodotin dose of 1.9 mg/kg instead of 2.5 mg/kg would result in reduction in probability of ≥ CR without reduction in oAEs/ophthalmic exam findings.</p><p><strong>Conclusions: </strong>An initial belantamab mafodotin dose of 2.5 mg/kg for BPd yields deeper responses versus 1.9 mg/kg with minimal change in safety outcomes in RRMM. DREAMM-8 (NCT04484623) was registered at clinicaltrials.gov (21 July 2020).</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"833-845"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elranatamab Fixed Dosing: A Safe, Effective, and Convenient Dosing Approach.","authors":"Mohamed Elmeliegy, Pooneh Soltantabar, Jennifer Hibma, Olivia Ashman, Diane Wang, Hoi-Kei Lon","doi":"10.1007/s11523-025-01170-4","DOIUrl":"10.1007/s11523-025-01170-4","url":null,"abstract":"<p><strong>Background: </strong>Bispecific T-cell engagers (TCEs) are a promising modality for cancer treatment, and evaluation of dosing strategies, including utilization of body weight-based versus fixed dosing, is essential to ensure optimal therapeutic outcomes. Elranatamab is a bispecific TCE that targets B-cell maturation antigen (BCMA) on multiple myeloma cells and CD on T cells. Elranatamab is approved for relapsed or refractory multiple myeloma (RRMM).</p><p><strong>Objective: </strong>Evaluate the impact of body weight on the pharmacokinetics (PK), safety, and efficacy of elranatamab.</p><p><strong>Patients and methods: </strong>Data from the phase 2 MagnetisMM-3 trial (NCT04649359) were used to evaluate the impact of body weight on the PK, safety, and efficacy of elranatamab. This trial comprised two cohorts: cohort A included patients who had not previously received BCMA-directed therapy and cohort B included patients who had received prior BCMA-directed therapies. All patients received a 76-mg fixed dose of subcutaneous elranatamab once weekly after a two-step priming dose regimen. Blood samples were collected from MagnetisMM-3 trial patients for PK analysis. This study analyzed the PK, efficacy, and safety of elranatamab across body weight quartiles.</p><p><strong>Results: </strong>The results demonstrated that when elranatamab was given at a fixed dose, the predose concentrations showed overlapping distributions with comparable medians, especially across the lowest three body weight quartiles, with a lower median for quartile 4, which was not considered clinically relevant. There were no clinically relevant differences in the safety profile between different body weight quartiles. With respect to efficacy, the overall response and complete response rates were comparable across body weight quartiles. A clinically meaningful objective response rate benefit with overlapping confidence intervals was observed across all four quartiles, consistent with the primary efficacy analysis. No trend was identified between body weight and progression-free survival and the duration of response on the basis of the Kaplan-Meier curves.</p><p><strong>Conclusions: </strong>Concerns with flat dosing include the potential for overdosing those with lower body weights and underdosing individuals with higher body weights. However, this study provides evidence that fixed dosing of elranatamab is effective and demonstrated a consistent and manageable safety profile across a broad range of body weights. There is no significant impact of body weight on the PK, safety, or efficacy of elranatamab. These findings support the approved fixed dosing of elranatamab in patients with RRMM.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov identifier: </strong>NCT04649359.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"821-831"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}