General Information

Zepzelca (lurbinectedin) is an alkylating drug that binds guanine residues within DNA.

Zepzelca is specifically indicated for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.

Zepzelca is supplied as an injection for intravenous infusion. The recommended dosage of Zepzelca is 3.2 mg/m2 by intravenous infusion over 60 minutes every 21 days until disease progression or unacceptable toxicity. Initiate treatment with Zepzelca only if absolute neutrophil count (ANC) is at least 1,500 cells/mm3 and platelet count is at least 100,000/mm3 .

Mechanism of Action

Zepzelca (lurbinectedin) is an alkylating drug that binds guanine residues in the minor groove of DNA, forming adducts and resulting in a bending of the DNA helix towards the major groove. Adduct formation triggers a cascade of events that can affect the subsequent activity of DNA binding proteins, including some transcription factors, and DNA repair pathways, resulting in perturbation of the cell cycle and eventual cell death.

Side Effects

Adverse effects associated with the use of Zelzelca may include, but are not limited to, the following:

leukopenia

lymphopenia

fatigue

anemia

neutropenia

increased creatinine

increased alanine aminotransferase

increased glucose

thrombocytopenia

nausea

decreased appetite

musculoskeletal pain

decreased albumin

constipation

dyspnea

decreased sodium

increased aspartate aminotransferase

vomiting

cough

decreased magnesium

diarrhea

Clinical Trial Results

Zepzelca for SCLC was approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The FDA approval of Zelzelca for SCLC was based a Phase 2 open-label, single-arm study, which enrolled a total of 105 SCLC patients at 26 hospitals in six European countries and the U.S. In the trial, platinum-sensitive and platinum-resistant patients were treated with Zepzelca 3.2 mg/m2, administered as a 60-minute IV infusion repeated every 21 days until disease progression or unacceptable toxicity. The primary endpoint, overall response rate (ORR), was 35 percent and the median duration of response was 5.3 months as measured by investigator assessment (30 percent and 5.1 months respectively, as measured by an IRC).