In short
Trilaciclib dihydrochloride (trilaciclib) is a kinase inhibitor that blocks the enzymes CDK4 and CDK6. It is an authorised medicine in the United States under the trade name Cosela for reducing chemotherapy-induced bone marrow suppression in extensive-stage small cell lung cancer. One registered clinical trial is now evaluating trilaciclib in 112 people with limited-stage small cell lung cancer.
Key points
- Trilaciclib is a CDK4/6 inhibitor that temporarily pauses bone marrow cells during chemotherapy.
- It is approved in the US as Cosela for extensive-stage small cell lung cancer.
- The registered trial is a Phase 3 study in limited-stage small cell lung cancer.
- The trial plans to enrol 112 participants receiving chemoradiotherapy.
- The main measures are severe neutropenia and its duration in the first treatment cycle.
- The trial is currently authorised but not yet recruiting.
What is trilaciclib dihydrochloride?
Trilaciclib dihydrochloride, known by the short name trilaciclib, is a kinase inhibitor. It belongs to the class of medicines called cyclin-dependent kinase (CDK) inhibitors, specifically blocking CDK4 and CDK6. The substance is also known by the development code G1T28 and the trade name Cosela. In the United States, trilaciclib received initial approval from the Food and Drug Administration (FDA) in 2021. It is classified in the Anatomical Therapeutic Chemical system under code V03AF12, in the group of detoxifying agents for antineoplastic treatment.
How does trilaciclib work?
Trilaciclib is a short-acting inhibitor of the enzymes CDK4 and CDK6. These enzymes control the cell cycle, the process by which cells divide. Bone marrow cells that produce blood cells, called hematopoietic stem and progenitor cells, depend on CDK4 and CDK6 to divide. By temporarily blocking these enzymes, trilaciclib pauses bone marrow cells in a resting state while chemotherapy is active. Because chemotherapy mainly harms dividing cells, the paused bone marrow cells are protected from damage. This helps preserve the bone marrow's ability to produce white blood cells called neutrophils, reducing the severity and duration of neutropenia, a condition of low neutrophil counts. Trilaciclib is described as a first-in-class medicine because it is the first approved drug to work in this way.
Which conditions is trilaciclib used or studied for?
- Extensive-stage small cell lung cancer — trilaciclib is approved in the United States to reduce the incidence of chemotherapy-induced myelosuppression in adults receiving a platinum/etoposide-containing regimen or a topotecan-containing regimen for this type of lung cancer.
- Limited-stage small cell lung cancer — a Phase 3 trial is now investigating whether trilaciclib can prevent myelosuppression in people receiving chemoradiotherapy for this earlier-stage form of the disease.
How is trilaciclib given?
Trilaciclib is given by intravenous infusion only. The approved product, Cosela, comes as a powder that is reconstituted into a solution. Each single-dose vial contains 300 mg of trilaciclib. The recommended dose described in the product information is 240 mg per square metre of body surface area, given as a 30-minute intravenous infusion completed no more than four hours before the start of chemotherapy on each day chemotherapy is administered. The dose is reduced in patients with moderate or severe liver impairment.
What do the clinical trials show?
One registered clinical trial of trilaciclib is listed in the registries. It is a Phase 3 interventional study comparing trilaciclib with placebo in people with limited-stage small cell lung cancer who are undergoing chemoradiotherapy. The trial plans to enrol 112 participants. The status of the trial is authorised, meaning it has received regulatory approval to proceed but is not yet recruiting.
The main outcomes measured are the duration of severe neutropenia in the first treatment cycle and the occurrence of severe neutropenia. Severe neutropenia means a very low level of neutrophils, the white blood cells that fight bacterial infections. The trial compares trilaciclib with a placebo, a substance with no active medicine, to see whether trilaciclib reduces bone marrow suppression during chemoradiotherapy.
What side effects are known?
The prescribing information for Cosela warns about injection-site reactions, including inflammation of the vein (phlebitis) and blood clots in the vein (thrombophlebitis). These reactions are monitored during infusion, and the infusion is stopped and the medicine permanently discontinued if a severe or life-threatening reaction occurs. Acute drug hypersensitivity reactions are also a concern. Signs include swelling of the face, eyes and tongue, hives and itching. People with a history of serious hypersensitivity reactions to Cosela should not receive the medicine.