Phase Ib study evaluating safety and clinical activity of the anti-HER3 antibody lumretuzumab combined with the anti-HER2 antibody pertuzumab and paclitaxel in HER3-positive, HER2-low metastatic breast cancer
Purpose To investigate the safety and clinical activity of comprehensive human epidermal growth factor receptor (HER) family receptor inhibition using lumretuzumab (anti-HER3) and pertuzumab (anti-HER2) in combination with paclitaxel in patients with metastatic breast cancer (MBC). Methods This phas...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
19 January 2018
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| In: |
Investigational new drugs
Year: 2018, Jahrgang: 36, Heft: 5, Pages: 848-859 |
| ISSN: | 1573-0646 |
| DOI: | 10.1007/s10637-018-0562-4 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1007/s10637-018-0562-4
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| Verfasserangaben: | Andreas Schneeweiss, Tjoung-Won Park-Simon, Joan Albanell, Ulrik Lassen, Javier Cortés, Veronique Dieras, Marcus May, Christoph Schindler, Frederik Marmé, Juan Miguel Cejalvo, Maria Martinez-Garcia, Iria Gonzalez, Jose Lopez-Martin, Anja Welt, Christelle Levy, Florence Joly, Francesca Michielin, Wolfgang Jacob, Céline Adessi, Annie Moisan, Georgina Meneses-Lorente, Tomas Racek, Ian James, Maurizio Ceppi, Max Hasmann, Martin Weisser, Andrés Cervantes |
MARC
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| 245 | 1 | 0 | |a Phase Ib study evaluating safety and clinical activity of the anti-HER3 antibody lumretuzumab combined with the anti-HER2 antibody pertuzumab and paclitaxel in HER3-positive, HER2-low metastatic breast cancer |c Andreas Schneeweiss, Tjoung-Won Park-Simon, Joan Albanell, Ulrik Lassen, Javier Cortés, Veronique Dieras, Marcus May, Christoph Schindler, Frederik Marmé, Juan Miguel Cejalvo, Maria Martinez-Garcia, Iria Gonzalez, Jose Lopez-Martin, Anja Welt, Christelle Levy, Florence Joly, Francesca Michielin, Wolfgang Jacob, Céline Adessi, Annie Moisan, Georgina Meneses-Lorente, Tomas Racek, Ian James, Maurizio Ceppi, Max Hasmann, Martin Weisser, Andrés Cervantes |
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| 520 | |a Purpose To investigate the safety and clinical activity of comprehensive human epidermal growth factor receptor (HER) family receptor inhibition using lumretuzumab (anti-HER3) and pertuzumab (anti-HER2) in combination with paclitaxel in patients with metastatic breast cancer (MBC). Methods This phase Ib study enrolled 35 MBC patients (first line or higher) with HER3-positive and HER2-low (immunohistochemistry 1+ to 2+ and in-situ hybridization negative) tumors. Patients received lumretuzumab (1000 mg in Cohort 1; 500 mg in Cohorts 2 and 3) plus pertuzumab (840 mg loading dose [LD] followed by 420 mg in Cohorts 1 and 2; 420 mg without LD in Cohort 3) every 3 weeks, plus paclitaxel (80 mg/m2 weekly in all cohorts). Patients in Cohort 3 received prophylactic loperamide treatment. Results Diarrhea grade 3 was a dose-limiting toxicity of Cohort 1 defining the maximum tolerated dose of lumretuzumab when given in combination with pertuzumab and paclitaxel at 500 mg every three weeks. Grade 3 diarrhea decreased from 50% (Cohort 2) to 30.8% (Cohort 3) with prophylactic loperamide administration and omission of the pertuzumab LD, nonetheless, all patients still experienced diarrhea. In first-line MBC patients, the objective response rate in Cohorts 2 and 3 was 55% and 38.5%, respectively. No relationship between HER2 and HER3 expression or somatic mutations and clinical response was observed. Conclusions Combination treatment with lumretuzumab, pertuzumab and paclitaxel was associated with a high incidence of diarrhea. Despite the efforts to alter dosing, the therapeutic window remained too narrow to warrant further clinical development. Trial registration: on ClinicalTrials.govwith the identifier NCT01918254 first registered on 3rd July 2013. | ||
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