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

An Open-Label, Phase 1 Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of ACC-1898 (Tyrosine Kinase Inhibitor) in Adult Participants With Advanced Solid Tumors.

This is a research study of an experimental drug called ACC-1898. ACC-1898 is an oral tyrosine kinase inhibitor (TKI) that blocks several proteins kinases which may help cancer cells grow and spread.

The purpose of this Phase 1 clinical trial is to find a safe dose of ACC-1898 and to understand how the body absorbs, distributes, and eliminates the drug (pharmacokinetics / PK). The study will also look for early signs that ACC-1898 may slow or shrink tumors and explore possible biological markers related to drug activity.

Adults with advanced or metastatic solid tumors who have no remaining standard treatment options may take part.

All participants will receive ACC-1898 tablets by mouth once daily in repeating 21-day cycles. Treatment may continue for up to two years if the cancer does not worsen and side effects are manageable.

Safety information, laboratory results and imaging scans (CT or MRI) will be collected regularly.

The study will first test different dose levels (dose-escalation phase) and may later expand enrollment in selected tumor types once a recommended dose is found.

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.

Inclusion Criteria (highlights):

Adults (≥ 18 years) with histologically confirmed advanced or metastatic solid tumors that have progressed after standard therapy or for which no effective standard option exists.

At least one measurable lesion per RECIST v1.1.

ECOG (Eastern Cooperative Oncology Group) Performance Status 0-1 (2 may be allowed with Medical Monitor approval).

Resolved acute effects from prior therapy to ≤ Grade 1 per CTCAE v5.0.

Adequate organ function (hematologic, hepatic, renal).

Able to swallow oral medication and comply with study requirements.

Signed informed consent.

Women of childbearing potential must have a negative pregnancy test and use highly effective contraception during and for 180 days after treatment; men must use condoms and avoid sperm donation for 120 days post-treatment.

Exclusion Criteria (highlights):

Known primary CNS (central nervous system) malignancy or symptomatic brain metastases requiring supraphysiologic steroids (unless stable ≥ 3 months after therapy).

Active or uncontrolled infection (including HBV, HCV, HIV) not meeting protocol control criteria.

HBV: Hepatitis B Virus HCV: Hepatitis C Virus HIV: Human Immunodeficiency Virus

Significant GI disease that could impair oral drug absorption (e.g., unresolved Grade > 1 nausea/diarrhea).

Active liver or biliary disease (except stable metastases or Gilbert's syndrome).

Baseline QTcF (QT Interval Corrected Using Fridericia Formula) > 450 msec (men) or > 470 msec (women), clinically significant ECG abnormalities, or heart rate < 45 bpm unless approved by cardiology review.

Pregnant or breastfeeding women.

Any other medical condition that, in the investigator's judgment, would interfere with study participation or pose unacceptable risk.