A Study of AN4035 in Advanced Cancers With RAS Mutations and High CEACAM5 Expression

NCT07686445 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: AN4035S0101
• Study Type: interventional
• Target: 228
• Locations: 1 country
• Sites: 2

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.

Conditions

CEACAM5; Solid Tumor (Phase I); RAS Mutation

Keywords

AN4035; Metastatic Solid Tumors

Outcome Measures

Primary Outcomes (2)

• 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

  28 Days after first dose

• Determination of the Maximum Tolerated Dose (MTD) for AN4035 as monotherapy

  Determination of the MTD for AN4035 by understanding the nature and frequency of dose limiting toxicity.

  28 days after the first dose for a specified dose level

Secondary Outcomes (8)

• Characterization of the PK profile of AN4035 following administration as an intravenous formulation

  At time points pre-dose, at End of Infusion (EOI), 2, 4, 6, 8, 24, 72, 168 hours post dose

• Characterization of the PK profile of AN9025 of AN4035 following administration as an intravenous formulation: steady state characterization

  At time points pre-dose, at End of Infusion (EOI), 2, 4, 6, 8, 24, 72, 168 hours post dose

• Characterization of the PK profile of AN4035 following administration as an intravenous formulation: drug level characterization in blood

  At time points pre-dose, at End of Infusion (EOI), 2, 4, 6, 8, 24, 72, 168 hours post dose

• Characterization of the PK profile of AN4035 following administration as an intravenous formulation: blood concentration characteristics

  At time points pre-dose, at End of Infusion (EOI), 2, 4, 6, 8, 24, 72, 168 hours post dose

• Characterization of the PK profile of AN4035 following administration as an intravenous formulation: drug half life determination

  At time points pre-dose, at End of Infusion (EOI), 2, 4, 6, 8, 24, 72, 168 hours post dose

Study Arms (2)

Monotherapy AN4035 Treatment

EXPERIMENTAL

Part 1 dose escalation and back-fill cohorts of varying doses of AN4035 intravenously dosed and Part 2 MTD for expansion cohorts.

Drug: Intravenous AN4035

Combination AN4035 + EGFR Inhibitor Treatment

EXPERIMENTAL

Part 1: Dose escalation and back-fill cohorts of varying doses of AN4035 intravenously dosed followed by intravenous administration of an EGFR Inhibitor. Part 2 MTD dosing for AN4035 followed by intravenous administration of an EGFR Inhibitor.

Drug: Intravenous AN4035 followed by intravenous EGFR Inhibitor.

Interventions

Intravenous AN4035 DRUG

AN4035 is a CAN4035 is a CEACAM5-targeting ADC designed to selectively deliver a proprietary pan-RAS(ON) inhibitor payload to tumor cells.

Monotherapy AN4035 Treatment

Intravenous AN4035 followed by intravenous EGFR Inhibitor. DRUG

AN4035 is a CAN4035 is a CEACAM5-targeting ADC designed to selectively deliver a proprietary pan-RAS(ON) inhibitor payload to tumor cells. EGFR inhibition and RAS signaling is mechanistically complementary, as EGFR functions upstream of RAS activation and may enhance pathway suppression and overcome therapeutic resistance.

Combination AN4035 + EGFR Inhibitor Treatment

Eligibility Criteria

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

You may qualify if:

• 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
• Colorectal cancer (CRC)
• Pancreatic ductal adenocarcinoma (PDAC)
• 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.

You may not qualify if:

• 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.
• Have tumors previously tested positive for Class I BRAF mutations i.e. V600X
• 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.
• 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 or syphilis infection per treponema pallidum particle agglutination (TPPA) and rapid plasma reagin (RPR)
• 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
• 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 trial, 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. calized prostate cancer) are eligible for this trial.
• Moderate or severe cardiovascular disease, such as the following:
• Congestive heart failure
• New York Heart Association Class III/IV heart disease
• Unstable angina pectoris

Sponsors & Collaborators

• Adlai Nortye Biopharma Co., Ltd.: lead

Study Sites (2)

Linear

Perth, Australia

Location

Scientia Clinical Research

Sydney, Australia

Location

Central Study Contacts

Adlai Study Manager

CONTACT

848 230-743; AN4035S0101@adlainortye.com

Study Design

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

Study Record Dates

• First Submitted: June 23, 2026
• First Posted: July 7, 2026
• Study Start (Estimated): September 23, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: July 14, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2)