دورية أكاديمية
A Phase I Trial of Nab-Paclitaxel/Bevacizumab (AB160) Nano-Immunoconjugate Therapy for Gynecologic Malignancies.
| العنوان: | A Phase I Trial of Nab-Paclitaxel/Bevacizumab (AB160) Nano-Immunoconjugate Therapy for Gynecologic Malignancies. |
|---|---|
| المؤلفون: | Kalogera E; Division of Gynecologic Surgery, Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota., Nevala WK; Department of Immunology, Mayo Clinic, Rochester, Minnesota., Finnes HD; Department of Pharmacy, Mayo Clinic, Rochester, Minnesota., Suman VJ; Division of Biomedical Statistics and Bioinformatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota., Schimke JM; Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota., Strand CA; Division of Biomedical Statistics and Bioinformatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota., Kottschade LA; Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota., Kudgus RA; Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota., Buhrow SA; Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota., Becher LR; Department of Immunology, Mayo Clinic, Rochester, Minnesota., Geng L; Department of Immunology, Mayo Clinic, Rochester, Minnesota., Glaser GE; Division of Gynecologic Surgery, Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota., Grudem ME; Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota., Jatoi A; Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota., Klampe CM; Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota., Kumar A; Division of Gynecologic Surgery, Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota., Langstraat CL; Division of Gynecologic Surgery, Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota., McWilliams RR; Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota., Wahner Hendrickson AE; Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota., Weroha SJ; Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota., Yan Y; Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota., Reid JM; Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota., Markovic SN; Department of Immunology, Mayo Clinic, Rochester, Minnesota.; Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota., Block MS; Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota. |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Jun 14; Vol. 30 (12), pp. 2623-2635. |
| نوع المنشور: | Journal Article; Clinical Trial, Phase I |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : The Association, c1995- |
| مواضيع طبية MeSH: | Paclitaxel*/administration & dosage , Paclitaxel*/adverse effects , Paclitaxel*/pharmacokinetics , Albumins*/administration & dosage , Albumins*/adverse effects , Genital Neoplasms, Female*/drug therapy , Genital Neoplasms, Female*/pathology , Bevacizumab*/administration & dosage , Antineoplastic Combined Chemotherapy Protocols*/adverse effects , Antineoplastic Combined Chemotherapy Protocols*/therapeutic use , Antineoplastic Combined Chemotherapy Protocols*/pharmacokinetics , Antineoplastic Combined Chemotherapy Protocols*/administration & dosage, Humans ; Female ; Middle Aged ; Aged ; Adult ; Immunoconjugates/administration & dosage ; Immunoconjugates/adverse effects ; Immunoconjugates/pharmacokinetics ; Immunoconjugates/therapeutic use ; Treatment Outcome ; Maximum Tolerated Dose |
| مستخلص: | Purpose: AB160 is a 160-nm nano-immunoconjugate consisting of nab-paclitaxel (ABX) nanoparticles noncovalently coated with bevacizumab (BEV) for targeted delivery into tissues expressing high levels of VEGF. Preclinical data showed that AB160 resulted in greater tumor targeting and tumor inhibition compared with sequential treatment with ABX then BEV. Given individual drug activity, we investigated the safety and toxicity of AB160 in patients with gynecologic cancers. Patients and Methods: A 3+3 phase I trial was conducted with three potential dose levels in patients with previously treated endometrial, cervical, and platinum-resistant ovarian cancer to ascertain the recommended phase II dose (RP2D). AB160 was administered intravenously on days 1, 8, and 15 of a 28-day cycle (ABX 75-175 mg/m2, BEV 30-70 mg/m2). Pharmacokinetic analyses were performed. Results: No dose-limiting toxicities (DLT) were seen among the three dose levels tested. Grade 3/4 toxicities included neutropenia, thromboembolic events, and leukopenia. DL2 (ABX 150 mg/m2, BEV 60 mg/m2) was chosen as the RP2D. Seven of the 19 patients with measurable disease (36.8%) had confirmed partial responses (95% confidence interval, 16.3%-61.6%). Pharmacokinetic analyses demonstrated that AB160 allowed 50% higher paclitaxel dosing and that paclitaxel clearance mirrored that of therapeutic antibodies. Conclusions: The safety profile and clinical activity of AB160 supports further clinical testing in patients with gynecologic cancers; the RP2D is DL2 (ABX 150 mg/m2, BEV 60 mg/m2). (©2024 The Authors; Published by the American Association for Cancer Research.) |
| References: | Am J Obstet Gynecol. 1994 Jun;170(6):1666-70; discussion 1670-1. (PMID: 7911273) Lancet Oncol. 2021 May;22(5):609-619. (PMID: 33845034) Lancet. 2017 Oct 7;390(10103):1654-1663. (PMID: 28756902) Curr Pharm Biotechnol. 2019;20(11):955-963. (PMID: 31322068) Sci Rep. 2017 Nov 3;7(1):14476. (PMID: 29101359) J Clin Oncol. 2011 Jun 1;29(16):2259-65. (PMID: 21537039) MAbs. 2014 Jan-Feb;6(1):34-45. (PMID: 24423619) Gynecol Oncol. 2006 Jun;101(3):436-40. (PMID: 16325893) J Clin Oncol. 2001 Oct 15;19(20):4048-53. (PMID: 11600606) Nat Rev Clin Oncol. 2010 Nov;7(11):653-64. (PMID: 20838415) Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):11982-7. (PMID: 23818604) Lab Invest. 1996 Jun;74(6):1105-15. (PMID: 8667614) Melanoma Res. 1997 Aug;7 Suppl 2:S19-26. (PMID: 9578413) J BUON. 2014 Oct-Dec;19(4):958-64. (PMID: 25536602) Anticancer Drugs. 1997 Aug;8(7):657-61. (PMID: 9311440) Ann Oncol. 2021 Jun;32(6):757-765. (PMID: 33667670) J Clin Oncol. 2014 May 1;32(13):1302-8. (PMID: 24637997) Cancer Res. 2016 Jul 1;76(13):3954-64. (PMID: 27197186) Gynecol Oncol. 2003 Mar;88(3):277-81. (PMID: 12648575) Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6152-7. (PMID: 19369214) Vasc Health Risk Manag. 2006;2(2):97-108. (PMID: 17319453) Clin Cancer Res. 2005 Jun 1;11(11):4136-43. (PMID: 15930349) Gynecol Oncol. 2012 Dec;127(3):451-5. (PMID: 22986144) Clin Cancer Res. 2011 Oct 15;17(20):6389-97. (PMID: 22003066) Gynecol Oncol. 2013 Feb;128(2):221-8. (PMID: 22960352) J Clin Oncol. 2007 Nov 20;25(33):5165-71. (PMID: 18024863) ChemMedChem. 2022 Jun 3;17(11):e202200032. (PMID: 35384350) Sci Rep. 2017 Apr 05;7:45682. (PMID: 28378801) Int J Oncol. 1999 Sep;15(3):595-9. (PMID: 10427146) Br J Cancer. 2000 Jul;83(2):196-203. (PMID: 10901370) J Clin Oncol. 2007 Nov 20;25(33):5180-6. (PMID: 18024865) Cancer Res. 1986 Aug;46(8):3751-5. (PMID: 3731053) Cancer Chemother Pharmacol. 2012 Feb;69(2):457-65. (PMID: 21853310) Br J Cancer. 2016 Feb 16;114(4):362-7. (PMID: 26742008) Nat Rev Drug Discov. 2006 Feb;5(2):147-59. (PMID: 16424916) J Clin Oncol. 2003 Sep 1;21(17):3194-200. (PMID: 12860964) Gynecol Oncol. 2011 Jul;122(1):111-5. (PMID: 21497382) Int J Clin Oncol. 2008 Feb;13(1):62-5. (PMID: 18307021) J Clin Oncol. 2023 May 1;41(13):2436-2445. (PMID: 36716407) Drug Discov Today. 2014 Jul;19(7):869-81. (PMID: 24239727) Melanoma Res. 1993 Feb;3(1):5-14. (PMID: 7682462) J Clin Oncol. 2004 Jun 1;22(11):2159-66. (PMID: 15169803) Clin Pharmacol Ther. 2008 Nov;84(5):548-58. (PMID: 18784655) J Clin Oncol. 2009 Oct 1;27(28):4649-55. (PMID: 19720909) |
| معلومات مُعتمدة: | P30 CA015083 United States CA NCI NIH HHS; Mayo Foundation for Medical Education and Research (MFMER) |
| المشرفين على المادة: | P88XT4IS4D (Paclitaxel) 0 (130-nm albumin-bound paclitaxel) 0 (Albumins) 2S9ZZM9Q9V (Bevacizumab) 0 (Immunoconjugates) |
| تواريخ الأحداث: | Date Created: 20240326 Date Completed: 20240614 Latest Revision: 20240726 |
| رمز التحديث: | 20240727 |
| مُعرف محوري في PubMed: | PMC11176914 |
| DOI: | 10.1158/1078-0432.CCR-23-3196 |
| PMID: | 38530846 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-3265 |
|---|---|
| DOI: | 10.1158/1078-0432.CCR-23-3196 |