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