A Study of AN4035 in Advanced Cancers With RAS Mutations and High CEACAM5 Expression
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorAdlai Nortye Biopharma Co., Ltd.
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
18 years old at the time of informed consent.
Colorectal cancer (CRC)
Pancreatic ductal adenocarcinoma (PDAC)
Non-small cell lung cancer (NSCLC)
Disqualifiers
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.
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)
Trial design
Design model
Single group
Treatments tested in this trial
Intravenous AN4035
DrugAN4035 is a CAN4035 is a CEACAM5-targeting ADC designed to selectively deliver a proprietary pan-RAS(ON) inhibitor payload to tumor cells.
Intravenous AN4035 followed by intravenous EGFR Inhibitor.
DrugAN4035 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.
Treatment groups
228 Participants
are divided into 2 treatment groupsGroup A: Monotherapy AN4035 TreatmentExperimental treatment 1 intervention
Group B: Combination AN4035 + EGFR Inhibitor TreatmentExperimental treatment 1 intervention
Trial outcomes
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
Time frame
28 Days after first dose2
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.
Time frame
28 days after the first dose for a specified dose levelSecondary outcomes
1
Characterization of the PK profile of AN4035 following administration as an intravenous formulation
The assessment will include, but not limit to, the following PK parameters for AN4035 - AUC(inf) after single dose and multiple doses Maximum blood concentration (Cmax) is reached.
Time frame
At time points pre-dose, at End of Infusion (EOI), 2, 4, 6, 8, 24, 72, 168 hours post dose2
Characterization of the PK profile of AN9025 of AN4035 following administration as an intravenous formulation: steady state characterization
Accumulation ratio (AR) at steady-state.
Time frame
At time points pre-dose, at End of Infusion (EOI), 2, 4, 6, 8, 24, 72, 168 hours post dose3
Characterization of the PK profile of AN4035 following administration as an intravenous formulation: drug level characterization in blood
Apparent clearance (CL/F) after single and multiple doses
Time frame
At time points pre-dose, at End of Infusion (EOI), 2, 4, 6, 8, 24, 72, 168 hours post dose4
Characterization of the PK profile of AN4035 following administration as an intravenous formulation: blood concentration characteristics
Time to maximum blood concentration (Tmax)
Time frame
At time points pre-dose, at End of Infusion (EOI), 2, 4, 6, 8, 24, 72, 168 hours post doseSponsors and contacts
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Source ClinicalTrials.gov
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