A5070373312- Cancer Genomics and Diagnostics
- Nuclear Structure and Function
- HER2/EGFR in Cancer Research
- Cancer therapeutics and mechanisms
- Peptidase Inhibition and Analysis
- Lung Cancer Research Studies
- Lung Cancer Treatments and Mutations
- Monoclonal and Polyclonal Antibodies Research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer Immunotherapy and Biomarkers
- Neuroendocrine Tumor Research Advances
- Glioma Diagnosis and Treatment
- Gastric Cancer Management and Outcomes
- Cancer Treatment and Pharmacology
- Advanced Breast Cancer Therapies
- Radiopharmaceutical Chemistry and Applications
- Colorectal Cancer Treatments and Studies
- Genetic factors in colorectal cancer
- Pancreatic and Hepatic Oncology Research
- Synthesis and biological activity
- CAR-T cell therapy research
- RNA Research and Splicing
- PARP inhibition in cancer therapy
- Cancer, Hypoxia, and Metabolism
- Multiple Myeloma Research and Treatments
Rigshospitalet
2016-2025
Copenhagen University Hospital
2016-2025
University of Copenhagen
1997-2023
Johns Hopkins Medicine
2023
Johns Hopkins University
2023
West Cancer Center
2019
Peter MacCallum Cancer Centre
2019
Dana-Farber Cancer Institute
2019
Memorial Sloan Kettering Cancer Center
2005-2019
Sorbonne Université
2019
Selective sequencing or in silico analysis for differences DNA fragment size can improve the detection of circulating tumor DNA.
Purpose This trial evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of selinexor (KPT-330), a novel, oral small-molecule inhibitor exportin 1 (XPO1/CRM1), determined recommended phase II dose. Patients Methods In total, 189 patients with advanced solid tumors received (3 to 85 mg/m 2 ) in 21- or 28-day cycles. Pre- post-treatment levels XPO1 mRNA patient-derived leukocytes were by reverse transcriptase quantitative polymerase chain reaction, tumor biopsies examined...
The aim of this clinical trial was to investigate safety and efficacy when combining cetuximab with bevacizumab irinotecan in patients recurrent primary glioblastoma multiforme (GBM). Patients were included GBM progression within 6 months ending standard treatment (radiotherapy temozolomide). Bevacizumab administered IV every 2 weeks. first 10 received 5 mg/kg, but increased mg/kg after interim analysis. Irinotecan dose based on whether taking enzyme-inducing antiepileptic drugs or not: 340...
Abstract HER2 mutations define a subset of metastatic breast cancers with unique mechanism oncogenic addiction to signaling. We explored activity the irreversible pan-HER kinase inhibitor neratinib, alone or fulvestrant, in 81 patients HER2-mutant cancer. Overall response rate was similar without estrogen receptor (ER) blockade. By comparison, progression-free survival and duration appeared longer ER+ receiving combination therapy, although study not designed for direct comparison....
Abstract Background This open-label, phase 1 trial (NCT02316197) aimed to determine the maximum-tolerated dose (MTD) and/or recommended 2 (RP2D) of peposertib (formerly M3814), a DNA-dependent protein kinase (DNA-PK) inhibitor in patients with advanced solid tumours. Secondary/exploratory objectives included safety/tolerability, pharmacokinetic/pharmacodynamic profiles and clinical activity. Methods Adult tumours received 100–200 mg once daily or 150–400 twice (BID) 21-day cycles. Results...
Abstract Purpose: We evaluated the clinical benefit of tumor molecular profiling to select treatment in phase I setting. Experimental Design: Patients with advanced solid cancers and exhausted options referred a unit were included prospective, single-center, single-arm open-label study (NCT02290522). Tumor biopsies obtained for comprehensive genomic analysis including whole-exome sequencing RNA sequencing. When possible, patients treated regimen matched profile. Primary endpoint was...
We retrospectively determined the efficacy and safety of a combination bevacizumab irinotecan in consecutive series 52 heavily pre-treated patients with recurrent high-grade brain tumours. Patients received (10 mg/kg) [340 mg/m(2) for those receiving enzyme-inducing antiepileptic drugs (EIAEDs) 125 not EIAEDs] every 2 weeks. Fifty-two were included 47 evaluable response.Complete or partial response was observed 25% all cases (30% grade IV glioma 15% III glioma). Estimated median...
Purpose: The high fatality-to-case ratio of ovarian cancer is directly related to platinum resistance. Exportin-1 (XPO1) a nuclear exporter that mediates export multiple tumor suppressors. We investigated possible clinicopathologic correlations XPO1 expression levels and evaluated the efficacy inhibition as therapeutic strategy in platinum-sensitive -resistant cancer.Experimental Design: were analyzed define correlates using both TCGA/GEO datasets tissue microarrays (TMA). effect inhibition,...
Abstract Background: Larotrectinib, a selective TRKi, is now FDA approved for pediatric and adult TRK-fusion solid tumors, regardless of tumor origin. Emergent TRK kinase mutations are common mechanism resistance to TRKis. LOXO-195, was developed maintain potency against multiple domain mutations. Methods: Patients (pts) received LOXO-195 via Phase I study (NCT03215511, n=20) or expanded access single patient protocol (SPP, n=11). Eligible pts were ≥4-weeks old with locally identified fusion...
Abstract Genomic screening of cancer patients for predisposing variants is traditionally based on age at onset, family history and type cancer. Whereas the clinical guidelines have proven efficient in identifying families exhibiting classical attributes hereditary cancer, frequency with alternative presentations unclear. We identified characterized germline 636 advanced solid using whole exome sequencing. Pathogenic likely pathogenic among 168 genes associated were considered. These 17.8%...
Abstract Purpose: Selinexor is an oral selective inhibitor of exportin-1 (XPO1) with efficacy in various solid and hematologic tumors. We assessed intratumoral penetration, safety, selinexor monotherapy for recurrent glioblastoma. Patients Methods: Seventy-six adults Karnofsky Performance Status ≥ 60 were enrolled. undergoing cytoreductive surgery received up to three doses (twice weekly) preoperatively (Arm A; n = 8 patients). not 50 mg/m2 B, 24), or mg C, 14) twice weekly, 80 once weekly...
Purpose: Simlukafusp alfa [fibroblast activation protein α–targeted IL2 variant (FAP-IL2v)], a tumor-targeted immunocytokine, comprising an moiety with abolished CD25 binding fused to human IgG1, is directed against fibroblast α. This phase I, open-label, multicenter, dose-escalation, and extension study (NCT02627274) evaluated the safety, pharmacokinetics, pharmacodynamics, antitumor activity of FAP-IL2v in patients advanced/metastatic solid tumors. Patients Methods: Participants received...
This phase I study assessed the maximum tolerated dose, dose-limiting toxicity (DLT) and pharmacokinetics of belinostat with carboplatin paclitaxel anti-tumour activity combination in solid tumours. Cohorts three to six patients were treated escalating doses administered intravenously once daily, days 1–5 q21 days; on day 3, (area under curve (AUC) 5) and/or (175 mg m−2) 2–3 h after end infusion. In all 23 received 600–1000 m−2 per paclitaxel. No DLT was observed. The maximal dose 1000 for...
A first-in-human phase I study was conducted to characterize safety, efficacy, and pharmacokinetic (PK) pharmacodynamic (PD) properties of lumretuzumab, a humanized glycoengineered anti-HER3 monoclonal antibody, in patients with advanced cancer.Twenty-five histologically confirmed HER3-expressing tumors received lumretuzumab (100, 200, 400, 800, 1,600, 2,000 mg) every two weeks (q2w) 3+3 dose-escalation phase. In addition, 22 were enrolled into an extension cohort at mg q2w.There no...