Study of ACC-1898 in Adult Participants With Advanced Solid Tumors

Study Design: ACC-1898-101 is an open-label, multicenter, interventional Phase 1 study sponsored by AccSalus Biosciences Inc. (IND #177222). The trial evaluates the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of ACC-1898 in adults with advanced solid tumors that are unresponsive to or ineligible for standard therapies. Rationale: Aberrant activation of receptor tyrosine kinases (RTKs) drives tumor proliferation, angiogenesis, and resistance to therapy. ACC-1898 (also known as ST-1898) is a small-molecule inhibitor designed to block several RTK pathways simultaneously. Nonclinical studies demonstrated broad antitumor activity and favorable oral bioavailability, while early clinical experience (≈ 100 patients in prior Asian trials) showed a manageable safety profile with preliminary efficacy. Objectives: Primary - determine the maximum tolerated dose (MTD) and/or optimal biologic dose (OBD) and characterize safety. Secondary - define PK parameters (Cmax, AUC, t½, CL/F, Vz/F) after single and repeated dosing. AUC: Area Under the Plasma Concentration-Time Curve t½: Terminal Elimination Half-Life CL/F: Apparent Oral Clearance Vz/F: Apparent Volume of Distribution Exploratory - evaluate objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and biomarker or PK/PD correlations. Methods: Approximately 40 participants will be enrolled during the dose-escalation part (Part 1) using an Accelerated Titration → Bayesian Optimal Interval (ATD (Accelerated Titration Design) -BOIN) design with planned dose levels of 80-300 mg once daily. Treatment continues in 21-day cycles until disease progression, unacceptable toxicity, withdrawal, or study completion. After identification of an MTD or recommended Part 2 dose, expansion cohorts may be opened for selected tumor types Assessments: Safety evaluations include adverse events (AEs), clinical laboratory tests, vital signs and imaging per RECIST (Response Evaluation Criteria in Solid Tumors) 1.1. PK sampling occurs intensively on Cycle 1 Day 1 and 15 and at steady-state in subsequent cycles. Duration: Each participant's involvement includes up to 28 days for screening, treatment for up to 2 years, and safety follow-up approximately 28 days after the last dose. Data Oversight: A Cohort Review Committee (CRC) serves as the data-monitoring body to review emerging safety and PK data before escalation or expansion decisions. Benefit-Risk Consideration: For patients with no remaining standard therapy, ACC-1898 offers a rational mechanism to target multiple oncogenic RTKs in a single oral agent. Known class-related risks are proactively managed through eligibility criteria, close monitoring, and prespecified dose-modification rules.