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

NCT07252479 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: AN9025S0101
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Solid Tumors (Phase 1); RAS Mutation

Keywords

RAS; RAS (ON); RAS Solid Tumor; KRAS G12X(C/D/V); KRAS G13D; NRAS Q61X(L/K); Oral Pan RAS medication

Outcome Measures

Primary Outcomes (1)

• • Nature and frequency of dose limiting toxicities (DLTs)

  • Incidence, nature, and severity of adverse events according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  21 days after first dose

Secondary Outcomes (9)

• Preliminary anti-tumor activity:Objective response rate (ORR)

  Tumor assessments will occur at baseline and then every 6 weeks starting from Cycle 3, Day 1 up to Cycle 9, Day 1 and then every 12 weeks thereafter (± 1 week window), through study completion, for an average duration of 1 year

• • Characterization of the PK profile of AN9025 following administration as an oral capsule formulation

  At time points pre-dose, 1, 2, 4, 6, 8, 24 hours post dose

• •Characterization of the PK profile of AN9025 following administration as an oral capsule formulation: steady state characterization

  At time points pre-dose, 1, 2, 4, 6, 8, 24 hours post dose

• Characterization of the PK profile of AN9025 following administration as an oral capsule formulation: drug level characterization in blood

  At time points pre-dose, 1, 2, 4, 6, 8, 24 hours post dose

• Characterization of the PK profile of AN9025 following administration as an oral capsule formulation

  At time points pre-dose, 1, 2, 4, 6, 8, 24 hours post dose

Other Outcomes (1)

• The identification of potential predictive biomarkers associated with response or resistance to AN9025

  Measured at baseline and evaluated at study completion, estimated at 2 years of first enrolled participant.

Study Arms (1)

AN9025 Treatment

EXPERIMENTAL

Oral administration of AN9025 capsules

Drug: AN9025 oral capsule

Interventions

AN9025 oral capsule DRUG

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.

AN9025 Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥18 years old at the time of informed consent.
• Able to provide informed consent voluntarily before any study-related activities and according to local guidelines.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Have an estimated life expectancy ≥ 12 weeks, in the judgment of the Investigator.
• Have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic with progression after treatment with available standard therapies.
• Documentation of KRAS/NRAS/HRAS mutation determined by validated local testing of tumor tissue or circulating free DNA (cfDNA) in a certified laboratory.
• Have consented to provide archival tumor tissue collected within 5 years or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
• Part 1 Dose-Escalation and Part 2 Food Effect Assessment: cancers including, but not limited to:
• Pancreatic ductal adenocarcinoma (PDAC)
• Colorectal cancer (CRC)
• Non-small cell lung cancer (NSCLC)
• Cutaneous melanoma
• Biliary tract cancer (BTC)
• Part 3 Dose-Expansion:
• Cohort 3A: RAS-mutated solid tumors (2L/3L)

You may not qualify if:

• Participants meeting any of the following criteria will not be eligible for participation in the study.
• Are currently enrolled in a clinical study involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study.
• Have tumors previously tested positive for Class I BRAF mutations i.e. V600X.
• Prior treatment with a pan-RAS(ON) inhibitor.
• Gastrointestinal conditions that may interfere with drug absorption (e.g., malabsorption syndrome, chronic nausea/vomiting, active inflammatory bowel disease).
• Have a serious concomitant systemic disorder that, in the judgment of the Investigator, would compromise the participant's ability to adhere to the protocol, such as the following:
• Known human immunodeficiency virus (HIV) infection per HIV 1 and/or 2 antibodies.
• Participants with evidence of active Hepatitis B or Hepatitis C infections (positive for Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody)
• Active tuberculosis, fungal infection
• Active infection requiring intravenous antibiotic therapy. Use of oral antibiotics for minor infections (e.g., uncomplicated UTI or URI) is permitted if clinically stable, at the Investigator's discretion
• The participant has a serious pre-existing medical condition(s) that, in the judgment of the Investigator, would preclude participation in this study, including interstitial lung disease (ILD), severe dyspnea at rest, or requiring oxygen therapy.
• Prior or second concurrent primary malignancies that, in the judgment of the Investigator, may affect the interpretation of results. Participants with carcinoma in situ of any origin and participants with prior malignancies who are in remission and whose likelihood of recurrence is very low (such as basal cell carcinoma), as judged by the Investigator, or malignancies that don't need treatment (i.e., small renal cell carcinoma \[RCC\] and localized prostate cancer) are eligible for this study.
• Moderate or severe cardiovascular disease, such as the following:
• congestive heart failure
• New York Heart Association Class III/IV heart disease

Sponsors & Collaborators

• Adlai Nortye Biopharma Co., Ltd.: lead

Study Sites (2)

Sarah Cannon Research Institute at Florida Cancer Specialists

Orlando, Florida, 32827, United States

RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

NOT YET RECRUITING

Central Study Contacts

Clinical Trial Manager

CONTACT

848 230-7430; AN9025S0101@adlainortye.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: November 26, 2025
• Study Start: January 28, 2026
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: February 11, 2026

Record last verified: 2026-02

Locations

US (2)