Nicolas Isambert

Nicolas Isambert
Centre Hospitalier Universitaire de Poitiers | CHU Poitiers · Pôle Régional de Cancérologie

MD, PhD

About

343
Publications
25,397
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8,700
Citations
Citations since 2016
165 Research Items
6679 Citations
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201620172018201920202021202202004006008001,0001,200
201620172018201920202021202202004006008001,0001,200

Publications

Publications (343)
Article
Introduction: Soft tissue sarcomas (STS) are a rare and heterogenous group of tumors, with poor prognostic, judging from their frequency to relapse. Few drugs are available after the conventional first line regimen. Since 2007, trabectedin got approval after failure of anthracyclines and ifosfamide, for advanced or metastatic STS. This led to a FD...
Article
Full-text available
Background BI 836880 is a humanized bispecific nanobody® that inhibits vascular endothelial growth factor and angiopoietin-2. Here, we report results from two phase I, nonrandomized, dose-escalation studies (NCT02674152 and NCT02689505; funded by Boehringer Ingelheim) evaluating BI 836880 in patients with confirmed locally advanced or metastatic so...
Article
Full-text available
Cancer progression is driven in part by genomic alterations¹. The genomic characterization of cancers has shown interpatient heterogeneity regarding driver alterations², leading to the concept that generation of genomic profiling in patients with cancer could allow the selection of effective therapies3,4. Although DNA sequencing has been implemente...
Article
Background: Preclinical studies showed that capmatinib reversibly inhibits cytochrome P450 (CYP) 3A4 and CYP1A2 in a time-dependent manner. In this study, we evaluated the effect of capmatinib on the exposure of sensitive substrates of CYP3A (midazolam) and CYP1A2 (caffeine), in patients with MET-dysregulated solid tumours. Besides pharmacokinetic...
Article
Full-text available
Background Palliative biliary drainage in patients with unresectable malignant biliary obstruction (MBO) frequently leads to biliary stent infection (BI), which could impact medical care. The aim of this study was to assess the risk factors for BI occurrence in patients after stenting procedure and the impact of BI on patient survival. Methods All...
Article
Background Metastatic leiomyosarcomas have a poor prognosis, and currently doxorubicin alone is used as the standard first-line treatment. Doxorubicin combined with trabectedin has shown promising results in phase 1 and 2 studies. We aimed to identify and compare the progression-free survival of patients with metastatic or unresectable uterine or s...
Article
Full-text available
Background Access to clinical trials and especially early-phase trials (ECT) is an important issue in geriatric oncology. As cancer can be considered an age-related disease because the incidence of most cancers increases with age, new drugs should also be evaluated in older patients to assess their safety and efficacy. The EGALICAN-2 study was prim...
Article
Background: Metastatic triple-negative breast cancer (mTNBC) is the most aggressive and heterogeneous breast cancer subtype, with limited therapeutic options. Immune-checkpoint inhibitors (ICI) with chemotherapy are approved as first-line therapy in mTNBC for patients with PD-L1+tumors. The generation of immunosuppressive extracellular adenosine in...
Article
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The phosphatidylinositol‐3‐kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is frequently activated in HER2‐negative breast cancer and may play a role in taxane resistance. The phase IB/II TAKTIC trial (NCT01980277) has shown that combining a dual AKT and p70 ribosomal protein S6 kinase (p70S6K) inhibitor (LY2780301) taken orally with...
Article
Full-text available
Background: Gynecological carcinosarcomas are rare and aggressive diseases, with a poor prognosis. The rarity of these tumors explains the lack of robust and specific data available in the literature. The objective of this study was to investigate the impact of initial adjuvant treatment and recurrent therapeutic strategies. Patients and methods:...
Article
Full-text available
Background Granulocyte colony‐stimulating factors (G‐CSF) are commonly given to limit chemotherapy‐induced neutropenia, but, in case of weekly chemotherapy such as eribulin, their administration schedules remain empirical. Objectives This pharmacokinetic/pharmacodynamic (PK/PD) study was conducted to establish the effect of different G‐CSF regimen...
Article
Full-text available
Background The phosphatidylinositol-3 kinase pathway is often altered in head and neck squamous cell carcinoma (HNSCC), and is involved in the resistance to EGFR inhibitors. Objective We investigated the dose-limiting toxicities (DLTs), maximum tolerated dose, pharmacokinetics, and preliminary efficacy of the combination of copanlisib, an intraveno...
Article
Background Hormone-resistant HER2-negative or triple-negative advanced breast cancers (ABC) are routinely treated with paclitaxel chemotherapy. LY2780301 is a dual inhibitor of p70 ribosomal protein S6 kinase and AKT. The TAKTIC study aimed at exploring the combination of paclitaxel and LY2780301 in this population. Methods In this multicentric ph...
Article
Full-text available
Background Malignant pleural mesothelioma (MPM) is an aggressive malignancy without curative treatment. Standard of care (SOC) include pemetrexed/cisplatin and nivolumab/ipilimumab with median overall survival in unresectable disease of 12.1 months and 18.1 months respectively. 1 2 ONCOS-102 is a granulocyte-macrophage colony stimulating factor (GM...
Article
Full-text available
Background Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β ”trap”) fused to a human IgG1 mAb blocking PD-L1. Here we report cumulative safety and pharmacokinetic (PK) results from the global, phase 1b/2 INTR@PID LUNG 024 study ( NCT03840915 ), which evaluated bin...
Article
The benefit of chemotherapy (CT) in rare bone sarcomas is not documented in prospective studies. This retrospective study from the French sarcoma network for bone tumors ResOs was performed in adult patients (pts) from 1976 to 2014, with histologically verified diagnosis of leiomyosarcomas (LMS), undifferentiated pleomorphic (UPS), or radiation-ass...
Article
Full-text available
Purpose European Organisation for Research and Treatment of Cancer (EORTC) 90101 (CREATE) was a prospective, multicentric, non-randomised, open-label phase II basket trial to assess the efficacy and safety of crizotinib in patients with different types of cancers, including advanced inflammatory myofibroblastic tumour (IMT) with or without anaplast...
Article
Full-text available
Background Granulocyte colony-stimulating factors (G-CSF) are commonly given to limit chemotherapy-induced neutropenia. However, for weekly chemotherapy such as eribulin, their administration schedules remain empirical. A pharmacokinetic/pharmacodynamic (PK/PD) study was conducted to establish the effect of different G-CSF regimens on neutropenia’s...
Article
Treatment options for metastatic osteosarcomas are scarce. Following failure of standard first line therapy, patients who relapse present a challenging treatment dilemma, and have a poor prognosis. Surgical removal of all metastases is essential. A retrospective analysis of patients with metastatic osteosarcomas was conducted in 15 French Sarcoma G...
Article
Full-text available
Background Uterine leiomyosarcomas (U-LMSs) and soft tissue leiomyosarcomas (ST-LMSs) are rare tumours with poor prognosis when locally advanced or metastatic, and with moderate chemosensitivity. In 2015 we reported very encouraging results of the LMS-02 study (NCT02131480) with manageable toxicity. Herein, we report the updated and long-term resul...
Conference Paper
Background: Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1. The global, phase 1b/2 INTR@PID LUNG 024 (NCT03840915) study evaluates bintrafusp alfa in combination with chemotherapy (CT) in patients with stage IV NS...
Article
Background Retrospective analyses suggest that patients with advanced KIT exon 9-mutated gastrointestinal stromal tumors (GISTs) receiving imatinib 800 mg (rather than 400 mg) daily have better outcomes. In the adjuvant setting, the question of the optimal dose of imatinib remains unsettled.Objective We aimed to retrospectively assess the activity...
Preprint
Full-text available
Background The phosphatidylinositol-3 kinase pathway is often altered in head and neck squamous cell carcinoma (HNSCC), and is involved in the resistance to EGFR inhibitors. Objective We investigated the dose-limiting toxicities (DLTs), maximum tolerated dose, pharmacokinetics, and preliminary efficacy of the combination of copanlisib, an intraveno...
Article
TPS3616 Background: METamp is a secondary, or co-driving, genetic change in pts with mCRC and acquired resistance to anti-EGFR therapy, which can contribute to disease progression. In EGFR-resistant pts with mCRC and METamp, MET inhibition + an anti-EGFR agent may achieve disease control by targeting emerging MET pathway activation and maintaining...
Article
6020 Background: Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1. A previous report of an expansion cohort from a phase 1 study (NCT02517398) suggested that bintrafusp alfa had a manageable safety profile and early...
Article
Full-text available
Background Esophageal adenocarcinoma patients have limited treatment options. TGF-β can be upregulated in esophageal adenocarcinoma, and blocking this pathway may enhance clinical response to PD-(L)1 inhibitors. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “tr...
Article
Background The French Sarcoma Group assessed the efficacy, safety, and quality of life (QoL) of trabectedin vs best supportive care (BSC) in patients with advanced soft-tissue sarcoma (STS). Patients and Methods This randomized, multicenter, open-label, phase III study included adults with STS who progressed after 1-3 prior treatment lines. Patien...
Article
Full-text available
Background The phase I trial of the humanized anti-CD26 monoclonal antibody YS110 for CD26-expressing tumors was conducted recently. The present study identifies a potential prognostic biomarker for CD26-targeted therapy based on the phase I data. Methods Box and Whisker plot analysis, Scatter plot analysis, Peason product moment correlation/Spear...
Article
Full-text available
The impact of single-agent antibodies against programmed death-ligand 1 (PD-L1) as maintenance therapy is unknown in patients with metastatic breast cancer. The SAFIR02-BREAST IMMUNO substudy included patients with human epidermal growth factor receptor type 2 (Her2)-negative metastatic breast cancer whose disease did not progress after six to eigh...
Article
TPS149 Background: METamp is a secondary, or co-driving, genetic change in pts with mCRC and acquired resistance to anti-EGFR therapy, which can contribute to disease progression. In EGFR-resistant pts with mCRC and METamp, MET inhibition + an anti-EGFR agent could achieve disease control by targeting emerging MET pathway activation and maintaining...
Article
329 Background: Tepotinib, a potent and highly selective MET inhibitor, showed promising activity in advanced HCC with MET overexpression in two Phase Ib/II trials, which both met their primary endpoints. One trial enrolled Asian patients (pts) without prior systemic therapy (first line [1L]; NCT01988493) and one enrolled US/European pts with prior...
Preprint
Full-text available
Background The phase I trial of the humanized anti-CD26 monoclonal antibody YS110 for CD26-expressing tumors was conducted recently. The present study identifies a potential prognostic biomarker for CD26-targeted therapy based on the phase I data. Methods Box and Whisker plot analysis, Scatter plot analysis, Peason product moment correlation/Spear...
Article
Full-text available
Hepatotoxicity is an important concern for nearly 40% of the patients treated with trabectedin for advanced soft tissue sarcoma (ASTS). The mechanisms underlying these liver damages have not yet been elucidated but they have been suggested to be related to the production of reactive metabolites. The aim of this pharmacogenetic study was to identify...
Poster
Full-text available
Immune activation was hallmarked by an increase in intra-tumoral cytotoxic T-cells and upregulation of adaptive immunity and cytotoxicity related gene expression along with polarization from M2 to M1 macrophage phenotype and upregulation of PD-L1 expression, indicating that ONCOS-102 is driving a favorable remodeling of the tumor microenvironment....
Article
Full-text available
Background Malignant pleural mesothelioma (MPM) is a rare, aggressive malignancy without curative treatment. Majority of patients receive pemetrexed/cisplatin as standard of care (SoC). Median overall survival in unresectable disease is 12 months. ONCOS-102 is a granulocyte-macrophage colony stimulating factor (GM-CSF) expressing oncolytic adenovir...
Article
Purpose: Lysine-specific demethylase 1 (LSD1) is implicated in multiple tumor types and its expression in cancer stem cells is associated with chemoresistance. CC-90011 is a potent, selective, and reversible oral LSD1 inhibitor. We examined CC-90011 in advanced solid tumors and relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL). Experimental des...
Article
Purpose: Lysine-specific demethylase 1 (LSD1) is implicated in multiple tumor types and its expression in cancer stem cells is associated with chemoresistance. CC-90011 is a potent, selective, and reversible oral LSD1 inhibitor. We examined CC-90011 in advanced solid tumors and relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL). Experimental de...
Article
OBJECTIVE. The response of desmoid tumors (DTs) to chemotherapy is evaluated with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) in daily practice and clinical trials. MRI shows early change in heterogeneity in responding tumors due to a decrease in cellular area and an increase in fibronecrotic content before dimensional res...
Article
Full-text available
Background We report the clinical activity and safety of bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of the transforming growth factor β (TGF-β)RII receptor (a TGF-β ‘trap’) fused to a human IgG1 monoclonal antibody blocking programmed death-ligand 1 (PD-L1), in patients with heavily pretreated...
Article
Full-text available
Exosomes are nanovesicles released by all cells that can be found in the blood. A key point for their use as potential biomarkers in cancer is to differentiate tumour-derived exosomes from other circulating nanovesicles. Heat shock protein-70 (HSP70) has been shown to be abundantly expressed by cancer cells and to be associated with bad prognosis....
Article
11506 Background: U-LMS and ST-LMS are rare tumors with poor prognosis when locally advanced or metastatic, and with moderate chemosensitivity. Overall response rates (ORR) given in the 1 st -line setting do not exceed 50% for U-LMS and 35% for ST-LMS with a mean response duration of 3- 6 months without impact on overall survival (OS). In 2015 we r...
Article
Full-text available
Background Uterine sarcomas are a group of rare tumors that include different subtypes. Patients with histopathological high-grade diseases are at high-risk of recurrence or progression, and have a poor prognosis. We aim to explore the most appropriate management in patients with uterine high-grade sarcomas. Primary objective To assess the efficac...
Article
Full-text available
Background: Cancer is the second leading cause of death globally. Early detection and disease management lead to a better survival rate. Consequently, discovery of novel methods in cancer early diagnosis is a field of active research. Minimally invasive liquid biopsies are generating growing interest. Circulating tumour cells (CTCs) have been iden...
Article
Background and purpose: Olaparib, a potent oral poly (ADP-ribose) polymerase inhibitor, is partially hepatically cleared. We investigated the pharmacokinetics (PK) and safety of olaparib in patients with mild or moderate hepatic impairment to provide dosing recommendations. Experimental approach: This Phase I open-label study assessed the PK, sa...
Conference Paper
Background: Approximately 10%-20% of breast cancers (BCs) are classified as triple-negative breast cancer (TNBC). TNBC lacks targeted treatment options and has a poor prognosis. Bintrafusp alfa (M7824) is an innovative first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to...
Article
Full-text available
Background: Brain metastases from sarcomatous lesions pose a management challenge owing to their rarity and the histopathological heterogeneity. Prognostic indices such as the Graded Prognostic Assessment (GPA) index have been developed for several primary tumour types presenting with brain metastases (e.g. lung, breast, melanoma), tailored to the...
Article
Background: Options in second-line therapy after doxorubicin-based chemotherapy for metastatic/advanced leiomyosarcoma include gemcitabine (G), trabectedin and pazopanib (P) monotherapy. Currently, no combination therapy is better than monotherapy. LMS03 is an open-label multicentre single-group phase II study designed to assess the efficacy and t...
Article
Background Metastatic phyllodes tumors have poor prognosis with median overall survival of 11.5 months. The objective of this study is to identify prognostic factors and the best options for management of metastatic malignant phyllode tumors (MMPTs). Patients and Methods A multicentric retrospective study, including cases of MMPT from 10 sarcoma c...
Article
Background CC-90011, a potent, selective, and reversible oral inhibitor of lysine-specific demethylase 1A, has shown antiproliferative activity against cancer cells in vitro and in patient (pt)-derived xenografts. Methods CC-90011-ST-001 is a phase I, first-in-human study of CC-90011 in ptswith advanced unresectable STs and R/R NHL. Pts received o...
Article
Background Genomically-guided clinical trials began to evaluate the efficacy of molecularly-targeted therapies across different tumor types sharing genetic mutations, but trial organisation remains complex. Here we address the feasibility and utility of routine somatic and constitutional exome analysis in a prospective cohort of metastatic cancer p...
Article
Background Epithelioid sarcoma (ES) is a rare soft-tissue sarcoma (STS) (1%). Few recent studies describe pathological and clinical characteristics of ES. Little is known about management and outcomes of patients with localized diseases. The objectives are to study tumor characteristics and clinical management of ES patients with local and locally-...
Article
Full-text available
Background Response of desmoid tumors (DT) to chemotherapy (CT) is evaluated according to RECIST criteria in daily practice and clinical trials. However, MRI demonstrates early change in heterogeneity in responding tumor, due to decrease in cellular area and increase in fibro-necrotic content, before dimensional response. Heterogeneity can be quant...