Phase 1b-2 Study of Safety and Preliminary Efficacy of LRK-4189 Alone or with Drug Combination in Patients with Solid Tumors

1 1 1 1

What is this study about?

The study focuses on patients with solid tumors, a type of cancer that forms a solid mass in organs, and includes a specific group with metastatic colorectal cancer, which is colon cancer that has spread to other parts of the body. The experimental medication being tested is an oral solution called LRK-4189. This drug may be given alone or together with standard chemotherapy combinations known as mFOLFOX6 and FOLFIRI. The mFOLFOX6 regimen contains the chemotherapy agents fluorouracil, oxaliplatin and folinic acid, while FOLFIRI includes fluorouracil, irinotecan and folinic acid. All of these medicines are given through an IV (a needle placed in a vein) and work by stopping cancer cells from growing.

The purpose of the study is to find a safe and effective dose of the new drug and to see how well it works against the cancers. This early‑stage trial uses a “dose‑escalation” approach, meaning the amount of the study drug is gradually increased in small groups of participants to identify the highest dose that can be given without unacceptable side effects. Participants will receive the medication in repeated treatment cycles, and doctors will monitor how the drug moves through the body (pharmacokinetics) and how it affects the cancer cells (pharmacodynamics).

After an initial screening, participants start treatment and return for regular visits where blood tests, imaging scans, and physical examinations are performed to track safety, side effects, and any changes in tumor size. The study continues through several cycles of treatment, with each cycle lasting a few weeks, until enough information is gathered to determine the appropriate dose for future larger trials.

1 baseline assessments

after enrollment, you undergo a series of baseline evaluations that include a physical examination, collection of medical history, laboratory tests, and imaging studies to document the status of the solid tumor before any study medication is given.

2 initiation of oral study medication

you begin taking the oral study drug lrk-4189 in solution form. the exact dose, frequency and length of each administration are defined by the study protocol and are provided by the trial staff. the medication is taken according to the schedule established for each treatment cycle.

3 administration of combination chemotherapy (if assigned)

if your treatment arm includes combination therapy, you receive intravenous chemotherapy that contains fluorouracil, oxaliplatin, and folinic acid (mFOLFOX6 regimen) or fluorouracil, folinic acid, and irinotecan (FOLFIRI regimen). each drug is given by IV injection or infusion as specified in the protocol. the dose and timing for each agent are determined by the study schedule and may be adjusted based on safety assessments.

4 safety and pharmacokinetic monitoring

throughout each treatment cycle you attend scheduled visits for safety monitoring. these visits include laboratory tests, assessment of adverse events, and collection of blood samples to measure drug levels (pharmacokinetics). the frequency of these visits follows the protocol and occurs before, during, and after each administration of study medication.

5 tumor response evaluation

imaging studies are performed at regular intervals to evaluate changes in tumor size according to the RECIST 1.1 criteria. the timing of each imaging assessment is defined by the study schedule and is used to determine objective response, disease control, and progression.

6 continuation of treatment cycles

you continue to receive the oral lrk-4189 and, if applicable, the intravenous chemotherapy in repeated cycles until one of the following occurs: disease progression, unacceptable toxicity, completion of the planned number of cycles, or a decision by the study team based on safety or efficacy considerations.

7 end‑of‑treatment visit

when treatment stops, a final assessment is performed. this includes a comprehensive physical exam, laboratory tests, imaging to document the final tumor status, and a review of all adverse events that occurred during the study.

8 post‑treatment follow‑up

after the end‑of‑treatment visit, you enter a follow‑up period during which periodic visits are scheduled to monitor long‑term safety and survival outcomes. the frequency of these follow‑up visits follows the protocol and may continue for several months after the last dose of study medication.

Who Can Join the Study?

Must be able and willing to sign the informed consent form, which explains the study and confirms your agreement to take part.
Must have adequate organ function at screening, meaning your liver, kidneys and other vital organs are working well enough for the trial.
Any side effects from previous cancer treatments, including nerve problems (peripheral neuropathy), must have improved to a mild level (Grade 1) or returned to baseline, except for hair loss (alopecia) and stable hormone problems caused by certain immune drugs (immune checkpoint inhibitors).
Female participants must either be unable to have children (non‑child‑bearing potential) or, if they could become pregnant, must agree not to try to become pregnant, not donate eggs, and use a highly effective birth‑control method from signing the consent until at least 6 months after the last study dose (9 months if they received oxaliplatin).
Male participants must agree not to donate sperm and, if they have sexual contact with a woman who could become pregnant, must use a condom and ensure the partner also uses a highly effective birth‑control method from signing the consent until at least 6 months after the last study dose (9 months if they received oxaliplatin).
Must be 18 years of age or older.
Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, indicating you are fully active or able to do light work.
Must have a tumor that is histologically proven (confirmed by a pathologist) to be locally advanced or metastatic (spread and not removable by surgery) and that has progressed after at least one standard treatment for advanced disease.
In the doctor’s view, you either cannot receive a benefit from standard therapy for medical reasons, or you have failed or could not tolerate one or more other cancer treatments.
Must have disease that can be measured using RECIST 1.1 criteria, a common method doctors use to track tumor size.
Must provide a sufficient sample of tumor tissue that is formalin‑fixed paraffin‑embedded (FFPE), taken after the last previous cancer treatment and before the first study dose, from a site that has not been previously irradiated.
Must agree to an on‑treatment biopsy if it is safe and feasible at the time of the biopsy.
Must have a QT interval corrected using the Fridericia method (QTcF) of 480 milliseconds or less, a heart electrical test that must be within a normal range.

Who Cannot Join the Study?

Cannot swallow or absorb the study drug because of other treatments you are taking or because of unusual anatomy that makes oral intake difficult.
Having an active infection that needs treatment through an IV (intravenous) line. If you are on oral antibiotics, you must have been without fever (afebrile) for at least three days before starting the study.
Taking strong medicines that affect drug metabolism (the way the body processes medication) that cannot be stopped at least 14 days before the study begins.
Being on therapeutic anticoagulation (blood thinners) that cannot be paused, because the study may require tissue samples (biopsies) to be taken safely.
Having a past or current surgical or medical condition that the doctor believes could interfere with the study results, increase your risk, or make it hard for you to attend study visits and follow instructions.
Being unable to follow the study schedule because of a psychiatric condition (mental health disorder) or substance abuse.
Being pregnant, breastfeeding, or planning to become pregnant or father a child during the study period and for three months afterward.
Having a medical reason that prevents you from receiving the chemotherapy regimens mFOLFOX6 or FOLFIRI, which are required for certain study groups.
Receiving the cancer drugs capecitabine or fluorouracil and having a known or test‑positive DPD deficiency (a condition where the body cannot break down these drugs properly).
Having a known allergic reaction (hypersensitivity) to the study drug LRK-4189 or any of its inactive ingredients (excipients).
Having a medical reason that makes repeated tissue sampling (serial biopsies) unsafe or impossible.
Having fluid buildup that causes symptoms (ascites in the abdomen or pleural effusion around the lungs) that required a therapeutic fluid removal procedure (paracentesis for abdomen or thoracentesis for chest) within the past six weeks.
Having active cancer spread to the brain or spinal fluid (central nervous system metastases or carcinomatous meningitis), or brain tumors that need treatment with steroids.
For the expansion part of the study only: having any other active cancer that needs systemic (whole‑body) treatment besides the colorectal cancer being studied.
Receiving any other anti‑cancer therapy at the same time as the study drug.
Having an active infection with HIV, hepatitis B, or hepatitis C as shown by a detectable amount of virus in the blood (viral load). Testing for these infections is not required for eligibility.
Using systemic corticosteroids (steroid medicines that affect the whole body) for inflammation or autoimmune problems within the past two weeks, or using other immune‑suppressing drugs within the past 30 days.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

No sites found in this category

Other Sites

Site Name	City	Country	Status
Centre Antoine Lacassagne	Nice	France
Les Hôpitaux Universitaires de Strasbourg	STRASBOURG, Alsace	France

Trial status

Country	Status	Recruitment Start
France	Not yet recruiting	30.06.2026

Trial locations

Investigated drugs:

LRK-4189 is an experimental oral medicine being studied for its ability to treat solid tumors, including metastatic colorectal cancer. In this trial the drug is given as a liquid you swallow, and researchers are looking at how safe it is, how the body handles it, and whether it can shrink tumors when used by itself or together with standard chemotherapy.

Fluorouracil is a chemotherapy drug that is delivered through an IV line. It works by stopping cancer cells from making the DNA they need to grow and divide. In this study it is part of the standard chemotherapy combinations that are given alongside LRK-4189.

Oxaliplatin is a platinum‑based chemotherapy drug given by IV infusion. It attaches to the DNA of cancer cells and prevents them from copying themselves, helping to kill the tumor. In the trial it is used as part of the mFOLFOX6 regimen that is combined with LRK-4189.

Folinic acid (also called leucovorin) is a vitamin‑like medication given by IV. It does not kill cancer cells directly, but it makes fluorouracil work better by helping it stay inside the cancer cells longer. It is included in both the mFOLFOX6 and FOLFIRI chemotherapy regimens used in the study.

Irinotecan is a chemotherapy drug administered through an IV infusion. It blocks an enzyme that cancer cells need to unwind their DNA, which stops the cells from growing and leads to their death. In this trial it is a key component of the FOLFIRI regimen that is tested together with LRK-4189.

Investigated diseases:

Colorectal cancer

Metastatic colorectal cancer – It begins as a cancer in the colon or rectum and later spreads to other parts of the body. The original tumor grows as a lump that can cause changes in bowel habits, bleeding, or weight loss. When cancer cells travel to organs such as the liver or lungs, new tumors form in those locations. The disease moves forward as both the original and new tumors become larger. Symptoms may become more noticeable as more organs are involved.

Solid tumor – A solid tumor is an abnormal mass of tissue that is not filled with fluid. These masses can arise in many organs, including the breast, lung, and colon. The tumor grows as cells divide, creating a lump that can be felt or seen on scans. Over time the mass may enlarge and press on nearby structures. If cancer cells break away, they can travel and create additional solid tumors in other parts of the body.

Trial ID:

2026-525629-20-00

Protocol code:

LRK-4189-102

NCT ID:

NCT07498725

Trial Phase:

Human Pharmacology (Phase I) – Other

Other Trials to Consider

#1 Clinical Trials Search in Europe

Phase 1b-2 Study of Safety and Preliminary Efficacy of LRK-4189 Alone or with Drug Combination in Patients with Solid Tumors

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?