NCT07252479

Evaluation of RAS Inhibitor Treatment in Participants With Advanced or Metastatic Solid Tumors Harboring RAS Mutations

A Multi-center, Open-label, Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of AN9025 in Participants With Advanced or Metastatic Solid Tumors Harboring RAS Mutations

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 91 (estimated)
• Sponsor: Adlai Nortye Biopharma Co., Ltd. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to learn determine if AN9025 is safe and tolerable to treat solid cancer tumors with specific genetic mutations. It will help identify doses for use in future testing and establish the safety profile of the drug. The main questions it aims to answer are: Which dose(s) of AN9025 are safe and tolerable for use in evaluating anti-tumor activity in participants with Rat Sarcoma oncogene (RAS) mutated solid tumors? What medical problems do participants have when taking AN9025? Participants will: Take AN9025 by mouth every day until their disease progresses, they experience severe ill side effects from taking the drug, or withdraw from the study due to their own choice or as recommended by their physician. Visit the clinic 3-4 times during the first 21 days of treatment for study testing, blood draws and tumor tissue sample collection (if needed). The blood draws will be used to check drug levels in the participants blood for research purposes. Visit the clinic every 21 days for checkups and tests and monitoring of participant progress. Return to the clinic at 14 and 30 days after AN9025 treatment is stopped. Participants will be contacted every 3 months to check on the participants disease status and general well being. Participants may also partake in a food effect study, where the effect of eating is studied to see if there is any effect on AN9025 in the body.

Detailed description

This is a first-in-human, open label, multi-center, multiple-ascending dose escalation, phase I study consisting of three parts: Part 1 Dose-Escalation, Part 2 Food Effect Assessment and Part 3 Dose-Expansion (See Figure 1, Figure 2, Figure 3 and Figure 4). The study is designed to evaluate the safety, tolerability, PK, and preliminary efficacy of AN9025, an oral pan-RAS (ON) inhibitor, in participants with advanced or metastatic solid tumors that harbor RAS mutations. In addition, the effect of food intake on the PK of AN9025 will be preliminarily investigated. The study will be conducted in the United States and China. Part 1 Dose-Escalation is designed to identify the Maximum Tolerated Dose (MTD) and/or Recommended Dose for Expansion (RDE) in participants with advanced or metastatic RAS-mutant solid tumors. Participants will be evaluated for Dose-limiting Toxicities (DLTs) in escalating dose and back fill cohorts. Participants enrolled in escalating dose cohorts will receive AN9025 with continuous once daily (QD) dosing in 21-day cycles. Participants enrolled in back fill cohorts will start with a single lead-in dose of AN9025 at least 5 days prior to initiating continuous QD dosing to enable PK sampling during the Single-Dose Lead-in period (Cycle 0). Following the Lead-in period, back fill participants will begin Cycle 1 Day 1 of the standard QD 21-day cycle treatment (Figure 3 A). Part 2 Food Effect Assessment will employ a single-sequence, two-period crossover design in at least 6 participants. Participants will begin with a Food Effect Lead-in period (Cycle 0), receiving a single-dose of AN9025 (at a selected dose level lower than the MTD) under fasting condition, followed by PK sample collection and a washout period. A second single-dose will then be administered under fed conditions, with additional PK sampling and another washout period. Upon completing this lead-in period, participants will transition to the main study treatment, initiating QD dosing from Cycle 1 Day 1 in 21-day cycles (Figure 3 B). Part 3 Dose-Expansion will evaluate the clinical activity of AN9025 in up to two RAS-mutated solid tumor indications using up to two dose levels selected based on the MTD/RDE established during dose escalation. This phase will further characterize the safety, tolerability, and PK of AN9025 in selected tumor types.

Conditions

• Solid Tumors (Phase 1)
• RAS Mutation

Interventions

Type	Name	Description
DRUG	AN9025 oral capsule	AN9025 is a novel, oral, small molecule pan-RAS (ON) inhibitor that binds cyclophilin A (CypA) with a slow dissociation rate, forming a tri-complex with guanosine triphosphate (GTP) bound state of both mutant and wild-type RAS proteins. AN9025 exhibits potent anti-proliferative activity in RAS-addicted cancer cell lines, demonstrates favorable pharmacokinetics (PK), pharmacodynamics and an acceptable tolerability profile in vivo.

Timeline

• Start date: 2026-01-28
• Primary completion: 2028-01-31
• Completion: 2028-06-01
• First posted: 2025-11-26
• Last updated: 2026-02-11

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study