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 or once a week 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.
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.
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, ) except for participants enrolled in the backfill cohorts who have experienced radiological or clinical disease progression on prior pan-RAS(ON) inhibitor therapy.
Gastrointestinal conditions that may interfere with drug absorption (e.g., malabsorption syndrome, chronic nausea/vomiting, active inflammatory bowel disease).
Single group
AN9025 oral capsule
DrugAN9025 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.
• 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
Preliminary anti-tumor activity:Objective response rate (ORR)
• Measure the Objective response rate (ORR)
• Characterization of the PK profile of AN9025 following administration as an oral capsule formulation
• The assessment will include, but not limit to, the following PK parameters for AN9025 \- AUC(inf) after single dose and AUC (0-τ) after single and multiple doses Maximum blood concentration (Cmax)
•Characterization of the PK profile of AN9025 following administration as an oral capsule formulation: steady state characterization
Accumulation ratio (AR) at steady-state
Characterization of the PK profile of AN9025 following administration as an oral capsule formulation: drug level characterization in blood
Apparent clearance (CL/F) after single and multiple doses
The identification of potential predictive biomarkers associated with response or resistance to AN9025
• Correlation of clinical outcomes with biomarkers to specific RAS mutation subtypes, and co-mutations in tumor tissue at baseline and progressive disease.
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