A Phase I/II Trial of BNC105P with Everolimus in Metastatic Renal Cell Carcinoma

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Sumanta PalThomas Hutson

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

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Citations

May 18, 2016·Expert Opinion on Investigational Drugs·Kunal NepaliJing-Ping Liou
Sep 28, 2017·Expert Opinion on Investigational Drugs·Michele GhidiniSandro Barni
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
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Nov 27, 2019·Pharmacology Research & Perspectives·Michael J Parnham, Gerd Geisslinger
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