Background: Following progression on Temozolomide (TMZ) glioblastoma (GBM) is a therapeutic challenge with a 6 month survival rate of only ~20-30% and no well-established 2nd line treatments. Methods: We designed a phase II study to assess the efficacy of cabazitaxel, a second generation taxoid, in TMZ-refractory GBM pts (pts). Primary enpoint was response at 12 weeks of treatment. Secondary endpoints were overall survival (OS), quality of life, and pharmacokinetics. The study population were pts with progressive GBM during or within 6 months after TMZ treatment, in whom radiotherapy and surgery was no treatment options. Exclusion criteria were signs of inflammation, an ECOG performance score (PS) > 2, as well as impaired organ function. Patient characteristics: In total, between 2014 and 2016 8 female and 16 male pts were included with a median age of 55 years (range 32-76 years) and a median of 3 previous therapies (range 1-9). Treatment: Cabazitaxel was given at 25mg/m² q3w with G-CSF prophylaxis. Every two cycles response assessment was performed (MRI). Treatment was discontinued in case of i) progressive disease (RANO criteria), ii) PS≥3, or iii) persistent toxicity. Results: Five pts went off study prior to the first MRI assessment due to progressive disease, while 19 of 24 of pts could be evaluated for response after 2 cycles. We did not observe any objective response (i.e. complete or partial remission). In 7 pts a stable disease (SD) was obtained; 12 pts had progressive disease. Of the 7 SD pts, 4 progressed after 4 cycles of treatment and the remaining pts remained in SD for 6, 10 and 12 cycles, respectively. The median OS was 155 days. Toxicity was manageable by G-CSF application in pts with CTC grade 3/4 neutropenia/leukopenia in 12 pts. Non-hematological toxicity CTC grade 3/4 comprised infection (n = 2), diarrhea (n = 2), vaginal bleeding (n = 1) and hypokalemia (n = 1). Conclusions: Cabazitaxel shows only marginal activity in TMZ refractory GBM with a disease stabilization rate following 4 cycles of only 12.5% in heavily pretreated GBM pts and median OS of 155 days. Clinical trial information: NCT 01866449.