In short
Entrectinib is an innovative targeted therapy drug being studied in clinical trials for the treatment of various solid tumors and non-small cell lung cancer (NSCLC), particularly in patients with specific genetic alterations. These trials aim to evaluate the safety, efficacy, and potential benefits of entrectinib in different patient populations and treatment scenarios.
At a glance
- Drug Name
- Entrectinib (also known as RXDX-101)
- Mechanism of Action
- Inhibitor of tyrosine kinases TrkA, TrkB, TrkC, ROS1, and ALK
- Target Patient Population
- Patients with solid tumors harboring NTRK1/2/3, ROS1, or ALK gene rearrangements
- Key Cancer Types Studied
- NSCLC, colorectal cancer, brain tumors, and various other solid tumors
- Administration
- Oral (capsules or tablets), typically daily dosing
- Primary Outcomes Measured
- Objective response rate, progression-free survival, safety and tolerability
- Secondary Outcomes
- Duration of response, overall survival, CNS efficacy in patients with brain metastases
- Special Considerations
- Efficacy in patients with CNS metastases, comparison with other targeted therapies (e.g., crizotinib)
- Patient Age Groups
- Studies include adult, pediatric, and adolescent patients
- Quality of Life Assessments
- Included in some trials using standardized questionnaires
What is Entrectinib?
Entrectinib is an oral medication used in the treatment of certain types of cancer. It is also known by its brand name Rozlytrek. Entrectinib belongs to a class of drugs called tyrosine kinase inhibitors, which work by targeting specific proteins in cancer cells to slow down or stop their growth.
How Does Entrectinib Work?
Entrectinib specifically targets and inhibits three types of proteins in cancer cells:
- TrkA, TrkB, and TrkC: These proteins are coded by genes called NTRK1, NTRK2, and NTRK3.
- ROS1: This protein is coded by the ROS1 gene.
- ALK: This protein is coded by the ALK gene.
When these proteins are altered or fused with other genes, they can cause uncontrolled cell growth, leading to cancer. By blocking the action of these proteins, entrectinib can help slow down or stop the growth of cancer cells.
What Conditions Does Entrectinib Treat?
Entrectinib is used to treat several types of cancers that have specific genetic alterations. These include:
- Non-small cell lung cancer (NSCLC) with ROS1 gene fusions
- Solid tumors with NTRK gene fusions, including:
- Colorectal cancer
- Salivary gland cancers
- Thyroid cancer
- Pancreatic cancer
- Brain tumors
- Sarcomas
Entrectinib is particularly effective in treating cancers that have spread to the brain (brain metastases) because it can cross the blood-brain barrier, a protective layer that prevents many drugs from reaching the brain.
Clinical Trials and Research
Several clinical trials have been conducted or are ongoing to evaluate the effectiveness and safety of entrectinib:
- STARTRK-2 Study: This global Phase 2 trial investigated entrectinib in patients with solid tumors harboring NTRK1/2/3, ROS1, or ALK gene fusions.
- STARTRK-NG Study: This Phase 1/2 trial evaluated entrectinib in children and adolescents with recurrent or refractory solid tumors and primary CNS tumors.
- ALKA-372-001 and STARTRK-1 Studies: These Phase 1 trials assessed the safety and efficacy of entrectinib in adult patients with locally advanced or metastatic solid tumors.
These trials have shown promising results, particularly in patients with ROS1-positive NSCLC and NTRK fusion-positive solid tumors.
How is Entrectinib Administered?
Entrectinib is taken orally in the form of capsules. The typical dosage for adults is 600 mg (three 200 mg capsules) once daily. For children and adolescents, the dosage is based on body surface area. The medication can be taken with or without food.
Potential Side Effects
Like all medications, entrectinib can cause side effects. Common side effects may include:
- Fatigue
- Constipation
- Altered sense of taste
- Swelling (edema)
- Dizziness
- Diarrhea
- Nausea
- Shortness of breath
- Muscle pain
- Cognitive changes
It's important to report any side effects to your healthcare provider. They can help manage these effects and may adjust your dosage if necessary.
Special Considerations
There are some special considerations to keep in mind when taking entrectinib:
- Genetic Testing: Before starting entrectinib, patients typically undergo genetic testing to confirm the presence of NTRK, ROS1, or ALK gene fusions in their tumors.
- Liver Function: Entrectinib is processed by the liver, so patients with liver problems may need dose adjustments.
- Pregnancy and Breastfeeding: The effects of entrectinib on unborn babies and breastfed infants are not well known. Patients who are pregnant, planning to become pregnant, or breastfeeding should discuss this with their doctor.
- Drug Interactions: Entrectinib may interact with other medications. It's important to inform your healthcare provider about all medications, supplements, and herbal products you are taking.