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ClinicalTrials.gov ID

NCT07686445

Lead Sponsor

Adlai Nortye Biopharma Co., Ltd.INDUSTRY

Overall Status

Not yet recruiting

Study Type

Interventional

Phase

Phase 1

Enrollment

228Estimated

Last Update Posted

Jul 14, 2026Actual

Start Date

Sep 23, 2026Estimated

Primary Completion Date

Dec 31, 2028Estimated

Completion Date

Dec 31, 2028Estimated

Official Title

A Multi-center, Open-label, Phase I Study Evaluating Safety, Tolerability, Pharmacokinetics and Antitumor Activity of AN4035 as Monotherapy or in Combination With Anticancer Agent(s) in Participants With Advanced or Metastatic Solid Tumors Harboring RAS Mutations and Enriched for CEACAM5 Expression

Brief Summary

The goal of this clinical trial is to determine whether AN4035 is safe and tolerable in people with advanced or metastatic solid tumors that have Rat Sarcoma oncogene (RAS) mutated solid tumors and high levels of the CEACAM5 protein. RAS genes help control how cells grow and divide. Mutations in RAS can cause cells to grow uncontrollably and contribute to cancer. CEACAM5 is a protein found on the surface of some cancer cells and may serve as a target for AN4035. This is the first time AN4035 is being tested in humans. The study will help identify the best dose(s) for future studies, understand how the body processes the drug, and evaluate whether AN4035 shows signs of fighting cancer.

The main questions to answer are:

• Which dose(s) of AN4035 are safe and tolerable for participants with RAS-mutated, CEACAM5-positive advanced solid tumors?
• What side effects or medical problems do participants experience while receiving AN4035 alone or in combination with cetuximab (Erbitux)?
• How does AN4035 move through and affect the body?
• Does AN4035 help slow, stop, or shrink tumors?

Participants will:

• Receive AN4035 by intravenous (IV) infusion every 2 weeks, either alone or in combination with commercially available drug cetuximab.
• Visit the clinic regularly for physical examinations, blood tests, safety assessments, and monitoring of their health and cancer status.
• Provide blood samples to measure drug levels and help researchers understand how the body processes AN4035.
• Undergo scans and other tests to evaluate how their tumors respond to treatment.
• Continue treatment until their cancer worsens, they experience unacceptable side effects, choose to leave the study, or their doctor recommends stopping treatment.
• Attend follow-up visits after treatment ends and may be contacted periodically to monitor their health and disease status.

The study has two parts. In the first part, researchers will gradually increase the dose of AN4035 to determine the highest dose that can be given safely and identify the recommended dose for future studies. This is done for just AN4035 and then for AN4035 + another Anti Cancer agent. In the second part, additional participants with selected tumor types will receive AN4035 at the chosen dose to further evaluate its safety and potential anti-cancer activity.

Detailed Description

This first-in-human (FIH) study aims to evaluate the safety, tolerability, Pharmacokinetics (PK), and preliminary anti-tumor activity of AN4035 administered as monotherapy or in combination with anticancer agent(s) in participants with advanced or metastatic solid tumors harboring RAS mutations and enriched for CEACAM5 expression. The study will identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) and establish proof of concept (PoC) for AN4035 monotherapy and combination therapy in selected tumor types. The study comprises a first-in-human dose escalation phase (Part 1) and a dose expansion phase (Part 2). The dose escalation phase is guided by A Bayesian Optimal Interval (BOIN) to determine the MTD and/or RDE.

• Part 1 Dose Escalation will identify the MTD and/or RDE of AN4035 as monotherapy or in combination with an EGFR inhibitor in participants with advanced or metastatic solid tumors that harbor RAS mutations and enriched for CEACAM5 expression. Part 1 has two parallel staggered escalation arms, with one arm of participants receiving escalating doses of AN4035 as monotherapy (Part 1a: AN4035 Monotherapy Dose Escalation) and one arm of participants receiving escalating doses of AN4035 in combination with standard dose of cetuximab (Part 1b: AN4035 + EGFR inhibitor Dose Escalation).
• Part 2 Dose Expansion will further optimize the AN4035 dose and evaluate the safety, tolerability, PK, and anti-tumor activity of AN4035 as monotherapy or in combination with an EGFR inhibitor in selected RAS-mutated and CEACAM5-enriched solid tumor types. Up to two dose levels may be explored in each arm (monotherapy and combination), with the specific doses selected based on the MTD and/or RDE established during Part 1 dose escalation.

Participants in Part 1a who experience progressive disease (PD), as determined by either clinical or radiographic evaluation during AN4035 monotherapy, will have the option to cross over into the backfill cohorts of Part 1b, provided that they meet the crossover eligibility criteria.

The trial will consist of a Screening period (up to 28 days prior to the initial study drug administration), a Treatment period, an End of Treatment (EoT) visit, a Safety Follow-up visit (within 30 days of last study drug) and a Survival Follow-up, up to 6 months after EoT or 12 months from Cycle 1 Day 1, whichever is longer.

• Solid Tumor (Phase I)
• RAS Mutation
• CEACAM5

• Intravenous AN4035
• Intravenous AN4035 followed by intravenous EGFR Inhibitor.

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria:

• 18 years old at the time of informed consent.

Able to provide informed consent voluntarily before any trial-related activities and according to local guidelines.

Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

Have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic with progression after treatment with available standard therapies or refuse standard therapies that are known to provide clinical benefit.

Documentation of KRAS/NRAS/HRAS mutation determined by a Sponsor-approved validated local testing of tumor tissue or cfDNA in a CLIA- or equivalently certified laboratory.

Dose Escalation: from cancers enriched for CEACAM5 expression

1. Colorectal cancer (CRC)
2. Pancreatic ductal adenocarcinoma (PDAC)
3. Non-small cell lung cancer (NSCLC)

Expansion Cohorts:

Histologically or cytologically confirmed advanced or metastatic CRC

Have failed two or more standard therapies regardless of prior use of targeted drugs such as cetuximab or bevacizumab.

Participants with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) must have also received prior treatment with immune checkpoint inhibitors or are ineligible for these therapies.

Prior treatment with a KRAS G12C inhibitor is permitted.

For a participant who has received neoadjuvant or adjuvant chemotherapy and had recurrence during or within 6 months of completion of therapy, the neoadjuvant or adjuvant chemotherapy should be counted as a regimen in the advanced setting.

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.

Have at least one measurable lesion as defined per RECIST v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

Adequate hematopoietic function per local laboratory

Have adequate organ functions prior to enrollment:

renal function per local laboratory glucose control per local laboratory (Part 1 only) liver function per local laboratory coagulation parameters pulmonary function cardiac function Total bilirubin (TBL) ≤ 1.5 × ULN Albumin ≥ 3 g/dL PT or aPTT ≤ 1.5 × ULN, or INR < 1.5 (unless on anticoagulants and values are within therapeutic range)

Have discontinued all previous treatments for cancer with resolution of any adverse events (AEs) to ≤ Grade 1 (except for alopecia, and endocrinopathies that are managed with replacement therapy) prior to enrollment

Fertile men and women of childbearing potential must agree to use an effective method of birth control from providing signed consent and for 180 days after the last trial intervention administration. Women of childbearing potential must have a negative pregnancy test ≤ 14 days prior to the first dose of the trial intervention.

Exclusion Criteria:

1. Are currently enrolled in a clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this trial.

2. Have tumors previously tested positive for Class I BRAF mutations i.e. V600X

3. Prior treatment with a pan-RAS(ON) inhibitor and pan-RAS(ON) inhibitor-based ADC are not permitted, except for participants enrolled in the backfill cohorts of Part 1a and Part 1b.

4. 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:

   1. Known human immunodeficiency virus (HIV) infection per HIV 1 and/or 2 antibodies or syphilis infection per treponema pallidum particle agglutination (TPPA) and rapid plasma reagin (RPR)

   2. Participants with evidence of Hepatitis B or Hepatitis C infections (positive for Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody) must fulfill the following criteria in order to be eligible for the trial:

      Hepatitis B virus (HBV) viral load ≤ 2500 copies or ≤ 500 IU/mL before trial enrollment, and participants with active HBV need to be on anti-HBV suppression ≥ 3 months, throughout treatment and for 6 months after. Hepatitis C virus (HCV) viral load ≤ lower limits of detection, participants with curable or controllable HCV infection are eligible. Participants with detectable HCV ribonucleic acid (RNA) can remain on continuous, effective antiviral therapy during the trial

   3. Active tuberculosis, fungal infection

   4. 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

5. The participant has a serious pre-existing medical condition(s) that, in the judgment of the Investigator, would preclude participation in this trial, including interstitial lung disease (ILD), severe dyspnea at rest, or requiring oxygen therapy.

6. Prior or second concurrent primary malignancies that, in the judgment of the Investigator, may affect the interpretation of results. calized prostate cancer) are eligible for this trial.

7. Moderate or severe cardiovascular disease, such as the following:

   1. Congestive heart failure
   2. New York Heart Association Class III/IV heart disease
   3. Unstable angina pectoris
   4. Myocardial infarction or cardiovascular event within the last 6 months before enrollment
   5. Valvulopathy that is severe, moderate, or deemed clinically significant
   6. Arrhythmias that are symptomatic or require treatment, except for rate-controlled supraventricular tachycardia and atrial fibrillation receiving anticoagulation
   7. A history of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of Long QT syndrome)
   8. Require the use of concomitant medications that prolong the QT/QTc interval

8. Uncontrolled pleural effusion, pericardial effusion or ascites requiring drainage. Participants who received drainage within 3 months of first dose should be excluded.

9. Have active central nervous system (CNS) malignancy or metastasis (e.g., new and/or progressive brain metastases). Participants with treated CNS metastases are eligible for this trial if they are not requiring concurrent treatment, including but not limited to surgery, radiation, corticosteroids and/or anticonvulsants to treat CNS metastases, and without evidence of progression for at least 30 days by repeat imaging.

10. Are pregnant or planning to become pregnant during trial or within 6 months following the last dose of AN4035. Plan to be breastfeeding from the initial dose of trial intervention or within 6 months following the last dose of AN4035.

11. Have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator.

12. Use of other herbal supplements, traditional medicines, or prescription medications that are known or suspected to interact with the investigational product or effect disease treatment/side effect management, as determined by the trial Investigator.

13. Known allergic reaction against any of the components of the trial interventions.

14. Use of drugs known to be strong inhibitors or inducers of isoenzyme cytochrome P450 3A4 (CYP3A4), or P-glycoprotein (P-gp) inhibitors, including herbal medications within 14 days (or 5 half-lives, whichever is longer) prior to the first dose of AN4035.

15. Participant is likely to not be available to complete all protocol-required trial visits or procedures, and/or to comply with all required trial procedures to the best of the participant and Investigator's knowledge.

Primary Purpose

Treatment

Allocation

Non-Randomized

Interventional Model

Single Group Assignment

Masking

None (Open Label)

Lead Sponsor

Adlai Nortye Biopharma Co., Ltd.INDUSTRY

contactus@scientiaclinicalresearch.com.au+61 2 9382 5800