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

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. 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. 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. 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.