Dendrimer-nanoparticle (DEP) delivery of cabazitaxel (DEP-cabazitaxel): A first-in-human phase 1/2 trial in patients with advanced solid tumours

Jones, Robert H. ORCID: https://orcid.org/0000-0003-3576-9496, Pinato, David J., Forster, Martin D., Joshua, Anthony M., Korolewicz, James, Aboud, Karam, Morton, Cienne, Liu, Jia, Cosman, Rasha, Benafif, Sarah, Edmondson, Stephanie R., Paull, Jeremy R.A., Main, Nicola J., Angeles, Julia and Spicer, James 2026. Dendrimer-nanoparticle (DEP) delivery of cabazitaxel (DEP-cabazitaxel): A first-in-human phase 1/2 trial in patients with advanced solid tumours. European Journal of Cancer 242 , 116821. 10.1016/j.ejca.2026.116821

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Abstract

Background This phase 1/2 trial evaluated safety, tolerability, pharmacokinetics, and antitumour activity of DEP-cabazitaxel (CTX-SPL9111), a dendrimer-cabazitaxel nanoparticle, in solid tumours. Methods Adult patients received DEP-cabazitaxel once every 3 weeks. The primary phase 1 objective was to establish the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs). Secondary objectives were to assess safety and tolerability, define the recommended phase 2 dose (RP2D), and evaluate pharmacokinetics and preliminary efficacy. Results Eighty-nine patients enrolled; most phase 2 patients had metastatic castrate-resistant prostate cancer (mCRPC; n = 25), platinum-resistant ovarian cancer (PROC; n = 22), or esophago-gastric cancer (EGC; n = 15). No DLTs were observed at the MTD and RP2D of 20 mg/m2 cabazitaxel. Most common treatment-emergent adverse events attributed to DEP-cabazitaxel were fatigue, peripheral neuropathy, nausea, anaemia, neutropenia, diarrhoea, and vomiting. In 75 phase 2 patients, Grade 3/4 neutropenia occurred in 22.7% and febrile neutropenia in 1.3%. In RECIST-evaluable phase 2 patients, the objective response rate (ORR) was 20% (9/45 measurable) and disease control rate (DCR) was 70.6% (36/51). By tumor type, ORRs were 16.7%, 17.6%, 30.0%, and 100% for mCRPC, PROC, EGC, and a thymic cancer patient, respectively. In evaluable phase 2 patients, 90.5% with mCRPC had PSA reductions (52.4% by >50%) and 86.7% had stable or improved bone metastases, and 75% with PROC had reduced CA‑125 or CEA. Median progression-free and overall survival were 3.8 and 9.0 months, respectively. Conclusion DEP-cabazitaxel was well tolerated and showed durable antitumour activity across advanced solid tumours, with reduced bone marrow toxicity compared to that reported for conventional cabazitaxel.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Publisher:	Elsevier BV
ISSN:	0959-8049
Date of Acceptance:	15 May 2026
Last Modified:	27 Jul 2026 21:15
URI:	https://orca.cardiff.ac.uk/id/eprint/187457

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