Dendrimer-nanoparticle (DEP) delivery of topoisomerase I inhibitor, SN38 (DEP-SN38): safety, tolerability, and preliminary efficacy study in patients with advanced solid tumors
Liu, J. Minchom, A. R. Greystoke, A. Evans, T. R. J. Sarker, D. Joshua, A. M. Morton, C. Yau, W. Aktas, B. Y. Cosman, R.
Liu, J.
Minchom, A. R.
Greystoke, A.
Evans, T. R. J.
Sarker, D.
Joshua, A. M.
Morton, C.
Yau, W.
Aktas, B. Y.
Cosman, R.
Abstract
PURPOSE: This early-phase study evaluated safety/tolerability, pharmacokinetics, and preliminary efficacy of dendrimer-nanoparticle delivery platform (DEP)-SN38, a polylysine-based nanoparticle conjugate of the irinotecan active metabolite, SN38. METHODS: Adults with advanced solid tumors received DEP-SN38 intravenously once every 3 weeks (Q3W) or once every 2 weeks (Q2W) monotherapy, or Q2W combined with fluorouracil/leucovorin (FU/LV) to identify a recommended dose for each regimen. Primary end points were safety/tolerability. Secondary end points included efficacy (RECIST-v1.1) and pharmacokinetics. RESULTS: Heavily pretreated patients (N = 114; median 4 previous therapies) received DEP-SN38 (8-15-mg/m(2) SN38), with 12.5 mg/m(2) recommended for all regimens. Most DEP-SN38-attributed treatment-related adverse events (TRAEs) were mild/moderate (89.7%), with neutropenia the key dose-limiting toxicity and the most common grade 3/4 TRAE (48% of grade 3/4 events). Severe GI TRAEs were rare (grade 3 diarrhea and vomiting [0.9% of patients each]; nausea [1.8%]). Cholinergic symptoms were not observed. Efficacy signals were observed across several tumor types, particularly Q2W regimens and in patients with platinum-resistant ovarian cancer (PROC) and colorectal cancer (CRC). Among evaluable patients, objective response rates for Q3W or Q2W monotherapy and Q2W DEP-SN38/FU/LV were 1.8%, 21.4% (PROC 42.9%), and 12.5% (CRC 14.3%), respectively; disease control rates were 56.4%, 71.4%, and 81.3%, respectively. Median progression-free survival (PFS, all treated) was 2.1, 6.0, and 4.2 months for Q3W, Q2W, and Q2W DEP-SN38/FU/LV, respectively. Patients achieving PFS for at least 6 months included seven PROC (Q2W monotherapy, n = 5; > 12 months, n = 3), 12 CRC (DEP-SN38/FU/LV, n = 6, including four patients for >12 months), one pancreatic (10.2 months), one non-small cell lung (8.4 months), and two with breast cancer (16.6 months, 6 months). CONCLUSION: DEP-SN38 was clinically well tolerated with minimal severe GI TRAEs. Preliminary antitumor activity in heavily pretreated patients with cancer demonstrates the potential clinical utility of DEP-SN38 monotherapy and combination regimens.
Description
Date
2025
Publisher
Collections
Keywords
Type
Article
Citation
Liu J, Minchom AR, Greystoke A, Evans TRJ, Sarker D, Joshua AM, et al. Dendrimer-Nanoparticle (DEP) Delivery of Topoisomerase I Inhibitor, SN38 (DEP-SN38): Safety, Tolerability, and Preliminary Efficacy Study in Patients With Advanced Solid Tumors. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2025 Sep 10;43(26):2918-29. PubMed PMID: 40749148. Epub 2025/08/01. eng.