677P - Preliminary findings from a phase I, open-label, dose-finding study of SNB-101 in patients with advanced solid tumors

Background

SNB-101 is a nanoparticle lyophilized injection of SN-38 (active metabolite of irinotecan), using polymer micelle technology, that is being developed to treat advanced solid tumors. The aim of this phase 1, dose-escalation study (SNB-101 101; NCT04640480) is to determine maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of SNB-101 in patients (pts) with advanced solid tumors.

Methods

SNB-101 101 is a 6-cohort, open-label, dose-escalation study with an estimated enrollment of up to 36 pts. Key eligibility criteria: age ≥18y; histologically/cytologically confirmed, locally advanced/metastatic disease progressing after standard systemic treatment; not suitable for complete surgical resection; measurable/evaluable disease (RECIST 1.1); ECOG PS 0/1. Pts receive SNB-101 i.v. (5/8 to 50/80 mg/m² SN-38/irinotecan HCl) d1&15 q28d, until progressive disease, unacceptable toxicity, death or consent withdrawal. An independent safety review committee determines dose escalation/de-escalation/modification and MTD/RP2D. Key efficacy outcomes: objective response rate (ORR); disease control rate (DCR); progression-free survival (PFS); overall survival (OS). Pharmacokinetic (PK) analysis of SN-38 and irinotecan is also performed.

Results

As of April 28, 2023, 21 pts have been enrolled/are evaluable. Most common treatment-related AEs: neutropenia (61.9%); white blood cell decreased (28.6%); nausea (23.8%); anemia (19.0%); platelet count decreased (19.0%). Most frequent grade 3/4 AEs: neutropenia (33.3%); white blood cell decreased (14.3%); platelet count decreased (9.5%). MTD was not reached after dose escalation at all planned doses. ORR is 14.3% and DCR is 42.9%, with 3 partial responses (SCLC, NSCLC, rectal) and 6 pts with stable disease (NSCLC, SCLC, tonsil, gastric x2, rectal). Median PFS and OS are 1.9 and 6.1 months, respectively. PK of SN-38 and irinotecan appears dose dependent.

Conclusions

SNB-101 was well tolerated; despite relatively high rates of hematological AEs, neutropenia was manageable. SNB-101 demonstrated antitumor efficacy, which appeared to be dose dependent. A phase 1b/2a trial combining SNB-101 with immunotherapy is planned.

Clinical trial identification

NCT04640480.

Editorial acknowledgement

Editorial assistance for this abstract was provided by Lee Miller (Miller Medical Communications Ltd.).

Legal entity responsible for the study

SN BioScience.

Funding

This work was funded by SN BioScience.

Disclosure

Y.H. Park, D. Heo, A. Kim, J. Kim: Financial Interests, Personal, Full or part-time Employment: SN BioScience. All other authors have declared no conflicts of interest.