On October 2, the U.S. Food and Drug Administration (FDA) approved lurbinectedin (Zepzelca) in combination with atezolizumab (Tecentriq) or atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza) for maintenance treatment of adults with extensive-stage small cell lung cancer (SCLC) whose disease has not progressed after first-line induction therapy with atezolizumab or atezolizumab and hyaluronidase-tqjs, carboplatin, and etoposide.
IMforte
Efficacy was evaluated in IMforte (ClinicalTrials.gov identifier NCT05091567), a randomized, multicenter, open-label trial in patients receiving first-line treatment for extensive-stage SCLC. In IMforte, 483 patients with extensive-stage SCLC whose disease had not progressed after completion of four cycles of atezolizumab, carboplatin, and etoposide (induction treatment) were randomly assigned 1:1 to receive either lurbinectedin in combination with atezolizumab administered intravenously (IV) or IV atezolizumab alone until disease progression or unacceptable toxicity.
The major efficacy outcome measures were overall survival and progression-free survival assessed by an independent review facility according to Response Evaluation Criteria in Solid Tumors version 1.1, measured from the time of randomization after completion of induction therapy. Median overall survival was 13.2 months (95% confidence interval [CI] = 11.9–16.4 months) in the lurbinectedin with atezolizumab arm and 10.6 months (95% CI = 9.5–12.2 months) in the atezolizumab arm (hazard ratio [HR] = 0.73, 95% CI = 0.57, 0.95; two-sided P = .0174). Median progression-free survival was 5.4 months (95% CI = 4.2–5.8 months) and 2.1 months (95% CI = 1.6–2.7 months) in the respective arms (HR = 0.54, 95% CI = 0.43–0.67; two-sided P < .0001).
The prescribing information for lurbinectedin includes warnings and precautions for myelosuppression, hepatotoxicity, extravasation resulting in tissue necrosis, rhabdomyolysis, and embryofetal toxicity. The prescribing information for atezolizumab and for atezolizumab and hyaluronidase-tqjs includes warnings and precautions for severe and fatal immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity.
The recommended lurbinectedin dose is 3.2 mg/m2 by IV infusion every 21 days until disease progression or unacceptable toxicity. The recommended atezolizumab dose is 840 mg every 2 weeks, 1,200 mg every 3 weeks, or 1,680 mg every 4 weeks by IV infusion until disease progression or unacceptable toxicity. The recommended dosage of atezolizumab and hyaluronidase-tqjs is 1,875 mg of atezolizumab and 30,000 units of hyaluronidase administered subcutaneously every 3 weeks until disease progression or unacceptable toxicity.
Expedited Programs
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence, which provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with Australia’s Therapeutic Goods Administration, Health Canada, Israel’s Ministry of Health, and Switzerland’s Swissmedic. The application reviews are ongoing at these agencies.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted Priority Review. Lurbinectedin and atezolizumab received Orphan Drug designation.
