Advanced Solid Tumor, Gall Bladder Cancer, Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Hepatocellular Carcinoma, Melanoma, Renal Cell Carcinoma, Thyroid Carcinoma, Medullary, Thyroid Carcinoma Primary Differentiated
Conditions
Keywords
Advanced Solid Tumors, Metastatic Cancer, Tyrosine Kinase Inhibitor, VEGFR, MET, RET, AXL, Multi-target TKI, ACC-1898
Brief summary
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.
Detailed description
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.
Interventions
DRUGACC-1898
ACC-1898 is an oral small-molecule tyrosine kinase inhibitor (TKI). Administered once daily by mouth in continuous 21-day cycles. Starting doses range from 80 mg to 300 mg QD, with possible intra-patient dose modifications. Arm(s)/Group(s): * Arm 1 - ACC-1898 Monotherapy * Arm 2 - ACC-1898 Monotherapy Route of Administration: Oral (tablet) Dose Form: Film-coated tablet (20 mg and 40 mg strengths) Treatment Duration: Up to 2 years or until disease progression or unacceptable toxicity.
Sponsors
AccSalus Biosciences, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study; no masking or blinding procedures are applied.
Intervention model description
Open-label, dose-escalation study followed by expansion at the recommended dose in participants with advanced solid tumors.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-Limiting Toxicities (DLTs) Part 1 (Dose Escalation) | Cycle 1 (each cycle = 21 days) | Occurrence of DLTs within the first treatment cycle to determine the maximum tolerated dose (MTD) and/or recommended Part 2 dose (OBD). |
| Treatment-Emergent Adverse Events (TEAEs) | From first dose through 28 days after last dose (up to 2 years) | Incidence, severity, and relationship of TEAEs graded per CTCAE v5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC₀-τ (steady-state interval) Part 1 (Pharmacokinetics) | Cycle 1 Day 15 (Cycle length = 21 days) | Exposure during one 24-hour dosing interval at steady state |
| AUC₀-∞ Part 1 (Pharmacokinetics) | Cycle 1 Day 1 (Cycle length = 21 days) | Total systemic exposure extrapolated to infinity after a single dose. |
| Terminal Half-Life (t½) Part 1 (Pharmacokinetics) | Cycle 1 Day 1 and Day 15 (Cycle length = 21 days) | Time for plasma concentration to decrease by 50 % during terminal phase. |
| Apparent Oral Clearance (CL/F) Part 1 (Pharmacokinetics) | Cycle 1 Day 15 (Cycle length = 21 days) | Dose/AUC representing systemic clearance after oral dosing. |
| Maximum Observed Plasma Concentration (Cmax) Part 1 (Pharmacokinetics) | Cycle 1 Day 1 and Day 15 (Cycle length = 21 days) | Maximum plasma concentration after oral dosing, derived from individual plasma concentration-time profiles. |
| Minimum Observed Plasma Concentration (Cmin) Part 1 (Pharmacokinetics) | Cycle 1 Day 15 (Cycle length = 21 days) | Trough plasma level within dosing interval at steady state. |
| Accumulation Ratio for AUC (AR-AUC) Part 1 (Pharmacokinetics) | Cycle 1 Day 15 vs Day 1 (Cycle length = 21 days) | Ratio of AUC after repeated versus single dosing. |
| Accumulation Ratio for Cmax (AR-Cmax) Part 1 (Pharmacokinetics) | Cycle 1 Day 15 vs Day 1 (Cycle length = 21 days) | Ratio of Cmax after repeated versus single dosing. |
| Apparent Volume of Distribution (Vz/F) Part 1 (Pharmacokinetics) | Cycle 1 Day 15 (Cycle length = 21 days) | Extent of drug distribution following oral administration. |
| Area Under the Concentration-Time Curve (AUC₀-last) Part 1 (Pharmacokinetics) | Cycle 1 Day 1 and Day 15 (Cycle length = 21 days) | Total drug exposure from dosing to last measurable concentration. |
Contacts
Primary ContactJaymes Holland
Backup ContactJaymes Holland
Outcome results
None listed