Abstract
BNC105P inhibits tubulin polymerization, and preclinical studies suggest possible synergy with everolimus. In this phase I/II study, efficacy and safety of the combination were explored in patients with metastatic renal cell carcinoma (mRCC). A phase I study in patients with clear cell mRCC and any prior number of therapies was conducted using a classical 3 + 3 design to evaluate standard doses of everolimus with increasing doses of BNC105P. At the recommended phase II dose (RP2D), patients with clear cell mRCC and one to two prior therapies (including ≥ 1 VEGF-TKI) were randomized to BNC105P with everolimus (arm A) or everolimus alone (arm B). The primary endpoint of the study was 6-month progression-free survival (6MPFS). Secondary endpoints included response rate, PFS, overall survival, and exploratory biomarker analyses. In the phase I study (N = 15), a dose of BNC105P at 16 mg/m(2) with everolimus at 10 mg daily was identified as the RP2D. In the phase II study, 139 patients were randomized, with 69 and 67 evaluable patients in arms A and B, respectively. 6MPFS was similar in the treatment arms (arm A: 33.82% vs. arm B: 30.30%, P = 0.66) and no difference in median PFS was observed (arm A: 4.7 mos vs. arm B: 4.1 mos; P = 0...Continue Reading
References
Feb 13, 2001·The American Journal of Pathology·J W SlatonC P Dinney
Nov 2, 2002·International Journal of Urology : Official Journal of the Japanese Urological Association·Xianghua ZhangYoshiyuki Kakehi
Sep 19, 2006·Urology·Nozomu KawataSatoru Takahashi
Oct 4, 2006·Nature Reviews. Drug Discovery·Scott WilhelmSusan Kelley
Jul 20, 2007·Cancer Chemotherapy and Pharmacology·Fanying MengCharles P Hart
Mar 12, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Anne O'DonnellIan Judson
Jul 26, 2008·Lancet·Robert J MotzerUNKNOWN RECORD-1 Study Group
Jun 3, 2010·Molecular Cancer Therapeutics·Gabriel KremmidiotisBernard Flynn
Jun 10, 2010·British Journal of Cancer·S L WoodR E Banks
Jun 22, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Danny RischinJayesh Desai
Nov 8, 2011·Lancet·Brian I RiniRobert J Motzer
Nov 16, 2011·Molecular Cancer Therapeutics·Leigh EllisRoberto Pili
Aug 18, 2012·Journal of Translational Medicine·Kiana KeyvanjahWilliam Carley
Mar 8, 2013·Oncology Reports·Inka ZoernigNiels Halama
Sep 12, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rachel E BeardRichard A Morgan
Dec 4, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Brian I RiniBernard Escudier
Dec 7, 2013·Cancer Biology & Therapy·Paul Dent
Mar 7, 2014·PloS One·Jeeyun LeeSung Kim
May 16, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·T K ChoueiriJ P Dutcher
Jul 25, 2014·International Journal of Molecular Sciences·Ilaria MarechGirolamo Ranieri
Citations
May 18, 2016·Expert Opinion on Investigational Drugs·Kunal NepaliJing-Ping Liou
Sep 28, 2017·Expert Opinion on Investigational Drugs·Michele GhidiniSandro Barni
Sep 9, 2017·PloS One·Billy AmzalHelene Karcher
Oct 29, 2018·Cancer Chemotherapy and Pharmacology·Kristina LindemannUNKNOWN For ANZGOG and HCRN Collaborative Groups
Sep 12, 2015·The Journal of Pharmacology and Experimental Therapeutics·Lisa M GreeneDaniela M Zisterer
Feb 20, 2018·Molecular Cancer·Khushwant S BhullarH P Vasantha Rupasinghe
Nov 27, 2019·Pharmacology Research & Perspectives·Michael J Parnham, Gerd Geisslinger
Dec 5, 2018·European Journal of Medicinal Chemistry·Florian SchmittThomas Mueller
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Li LiuRalph P Mason
Oct 16, 2020·The Cochrane Database of Systematic Reviews·Fabian HofmannBörje Ljungberg
Jun 11, 2021·Molecular Cancer Therapeutics·Eddy S YangGuru P Sonpavde