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Phase Ib clinical trial of the anti-frizzled antibody vantictumab (OMP-18R5) plus paclitaxel in patients with locally advanced or metastatic HER2-negative breast cancer.
Diamond, Jennifer R; Becerra, Carlos; Richards, Donald; Mita, Alain; Osborne, Cynthia; O'Shaughnessy, Joyce; Zhang, Chun; Henner, Randall; Kapoun, Ann M; Xu, Lu; Stagg, Bob; Uttamsingh, Shailaja; Brachmann, Rainer K; Farooki, Azeez; Mita, Monica.
Afiliación
  • Diamond JR; University of Colorado Anschutz Medical Campus, University of Colorado Cancer Center, 12801 E 17th Ave, Mailstop 8117, Aurora, CO, 80045, USA. Jennifer.diamond@cuanschutz.edu.
  • Becerra C; Baylor Sammons Cancer Center, Texas Oncology, US Oncology, Dallas, TX, USA.
  • Richards D; Texas Oncology, US Oncology, Tyler, TX, USA.
  • Mita A; Samuel Oschin Comprehensive Cancer Institute, 8700 Beverly Blvd, SCCT Mezzanine MS 35, Los Angeles, CA, 90048, USA.
  • Osborne C; Baylor Sammons Cancer Center, Texas Oncology, US Oncology, Dallas, TX, USA.
  • O'Shaughnessy J; Baylor Sammons Cancer Center, Texas Oncology, US Oncology, Dallas, TX, USA.
  • Zhang C; OncoMed Pharmaceuticals, Redwood City, CA, USA.
  • Henner R; OncoMed Pharmaceuticals, Redwood City, CA, USA.
  • Kapoun AM; OncoMed Pharmaceuticals, Redwood City, CA, USA.
  • Xu L; OncoMed Pharmaceuticals, Redwood City, CA, USA.
  • Stagg B; OncoMed Pharmaceuticals, Redwood City, CA, USA.
  • Uttamsingh S; OncoMed Pharmaceuticals, Redwood City, CA, USA.
  • Brachmann RK; OncoMed Pharmaceuticals, Redwood City, CA, USA.
  • Farooki A; Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Mita M; Samuel Oschin Comprehensive Cancer Institute, 8700 Beverly Blvd, SCCT Mezzanine MS 35, Los Angeles, CA, 90048, USA. Monica.mita@cshs.org.
Breast Cancer Res Treat ; 184(1): 53-62, 2020 Nov.
Article en En | MEDLINE | ID: mdl-32803633
PURPOSE: Vantictumab is a monoclonal antibody that binds to frizzled (FZD) receptors and inhibits canonical WNT signaling. This phase Ib dose escalation study enrolled patients with locally recurrent or metastatic HER2-negative breast cancer who were treated with weekly paclitaxel in combination with escalating doses of vantictumab. METHODS: Patients were enrolled in dose escalation cohorts treated with weekly paclitaxel 90 mg/m2 on days 1, 8 and 15 in combination with vantictumab 3.5-14 mg/kg days 1 and 15 or 3-8 mg/kg day 1 of every 28-day cycle. Primary endpoints were safety, dose-limiting toxicities (DLTs). Secondary endpoints included pharmacokinetics, efficacy and an exploratory biomarker analysis. RESULTS: Forty-eight female patients with a mean age of 54 were enrolled. The majority (66.6%) received prior chemotherapy for recurrent or metastatic disease; 45.8% were hormone receptor (HR)-positive, HER2-negative and 54.2% triple-negative. The most frequent adverse events related to any study treatment were nausea (54.2%), alopecia (52.1%), fatigue (47.9%), and peripheral neuropathy (43.8%). No DLTs occurred; however, 6 patients experienced fractures outside of the DLT window. The overall response rate was 31.3% and the clinical benefit rate was 68.8%. A 6-gene WNT pathway signature showed significant association with progression-free survival (PFS) and overall survival (OS) for the biomarker high versus biomarker low groups (PFS: p = 0.029 and OS: p = 0.00045, respectively). CONCLUSIONS: The combination of vantictumab and weekly paclitaxel was generally well tolerated with promising efficacy; however, the incidence of fractures limits future clinical development of this particular WNT inhibitor in metastatic breast cancer. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov registration: NCT01973309.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Paclitaxel Límite: Female / Humans Idioma: En Revista: Breast Cancer Res Treat Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Paclitaxel Límite: Female / Humans Idioma: En Revista: Breast Cancer Res Treat Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos