Phase 1/1B trial of the heat shock protein 90 inhibitor NVP-AUY922 as monotherapy or in combination with bortezomib in patients with relapsed or refractory multiple myeloma

Ruth Seggewiss-Bernhardt, Ralf C Bargou, Yeow Tee Goh, A Keith Stewart, Andrew Spencer, Adrian Alegre, Joan Blade, Oliver G Ottman, Cristina Fernandez-Ibarra, Hong Lu, Scott Pain, Mikhail Akimov, Swaminathan Padmanabhan Iyer

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    Abstract

    BACKGROUND NVP-AUY922 (AUY; Luminespib) with or without bortezomib showed preclinical activity against multiple myeloma (MM) cells. This phase 1/1B study assessed NVP-AUY922 alone and with bortezomib in patients with relapsed or refractory MM. METHODS Dose escalation was guided by an adaptive Bayesian logistic regression model. In phase 1, patients who progressed after 2 to 4 prior therapies received NVP-AUY922 intravenously once weekly. In phase 1B, patients who progressed after 2 or fewer prior therapies received NVP-AUY922 plus bortezomib. The primary objective was to determine the maximum tolerated dose (MTD) of NVP-AUY922. RESULTS Twenty-four patients received NVP-AUY922 monotherapy at doses of 8 to 70 mg/m2. One dose-limiting toxicity (DLT) was observed (grade 3 blurred vision at 70 mg/m2); no MTD was reached. The recommended phase 2 dose was 70 mg/m2. The most frequent drug-related adverse events (AEs) were diarrhea, nausea, and ocular toxicities. Grade 3/4 AEs were uncommon (
    Original languageEnglish
    Pages (from-to)2185 - 2192
    Number of pages8
    JournalCancer
    Volume121
    Issue number13
    DOIs
    Publication statusPublished - 2015

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