Lurbinectedin Combo Yields Significant OS/PFS in ES-SCLC

Developers plan to submit a supplemental NDA for this combination as a first-line maintenance therapy for ES-SCLC in the first half of 2025.

Lurbinectedin (Zepzelca) combined with atezolizumab (Tecentriq) produced statistically significant overall survival (OS) and progression-free survival (PFS) benefits compared with atezolizumab alone for the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) following induction therapy, according to a news release from the drug’s developer, Jazz Pharmaceuticals, on results from the phase 3 IMforte trial (NCT05091567).¹

The positive interim results from the trial support the developer’s plan to submit a supplemental new drug application (sNDA) for the combination as a first-line maintenance therapy for patients with ES-SCLC in the first half of 2025.

"Each year, approximately 30,000 new cases of SCLC are reported in the [United States]. A majority of these patients are diagnosed with extensive-stage disease, which is aggressive and often difficult to treat, with poor prognosis," lead trial investigator Luis Paz-Ares, MD, PhD, head of medical oncology at the Hospital Universitario 12 de Octubre in Madrid, Spain, said in the news release on the findings.¹ "These trial results demonstrate the efficacy of lurbinectedin, the most widely used agent in second-line SCLC in the United States, in combination with standard-of-care atezolizumab for patients in first-line maintenance treatment, a much-needed advancement for patients with extensive disease."

Investigators of the open-label, multi-center phase 3 IMforte trial randomly assigned patients with ES-SCLC 1:1 to receive either 1200 mg of intravenous atezolizumab once every 3 weeks plus 3.2 mg/m2 of intravenous lurbinectedin every 3 weeks or 1200 mg of intravenous atezolizumab alone once every 3 weeks.² Prior to receiving either maintenance therapy, all patients were initially treated with four 21-day cycles of atezolizumab at 1200 mg intravenously plus carboplatin and etoposide as induction therapy. Patients with ongoing responses or stable disease were then randomly assigned to the investigational or control groups.

The study’s co-primary end points were independent review facility–assessed PFS and OS. Secondary end points included investigator-assessed PFS, confirmed objective response rate (ORR), duration of response (DOR) for patients with confirmed responses, and incidence and severity of adverse events (AEs).

Preliminary safety data showed that the tolerability of the lurbinectedin combination was consistent with the known safety profiles of lurbinectedin and atezolizumab. No new safety signals were found.

Key inclusion criteria for the induction phase included histologically or cytologically confirmed ES-SCLC, adequate hematologic and end-organ function, and a treatment-free period of 6 or more months since prior chemotherapy/radiotherapy with curative intent for limited-stage SCLC. Additional criteria included no prior systemic therapy for ES-SCLC and an ECOG performance status of 0 or 1.

Key exclusion criteria for the induction phase included having any central nervous system metastases, active or prior autoimmune disease or deficiency, and prior treatment with CD137 agonists or immune checkpoint blockade therapies, among other criteria.

Of note, inclusion criteria for the maintenance phase included a resolution of toxicities attributed to prior induction therapy to grade 1 or less. Additionally, patients were excluded from the maintenance phase if they received consolidative chest radiation or if they had lesions requiring management with palliative radiotherapy.

"The results of the phase 3 IMforte trial are highly encouraging and showed a statistically significant benefit for the [lurbinectedin] and atezolizumab combination for [patients with ES-SCLC] receiving this treatment in the first-line maintenance setting,” Rob Iannone, MD, MSCE, executive vice president, global head of research and development, and chief medical officer at Jazz Pharmaceuticals, said in the news release.1 “We are pleased with these clinically meaningful results and plan to submit an sNDA in the first half of 2025 to support this combination in the first-line maintenance setting. We thank the investigators and patients who are involved in this trial, along with our partners at Roche."

Jazz and Roche plan to submit the study data for presentation at a future medical meeting.

References

1. Jazz Pharmaceuticals announces statistically significant overall survival and progression-free survival results for Zepzelca® (lurbinectedin) and atezolizumab combination in first-line maintenance therapy for extensive-stage small cell lung cancer. News release. Jazz Pharmaceuticals. October 15, 2024. Accessed October 15, 2024. https://tinyurl.com/3nss29jt
2. Paz-Ares L, Reck M, Peters S, et al. IMforte: a phase III study of lurbinectedin and atezolizumab versus atezolizumab as maintenance therapy in ES-SCLC. Presented at: World Conference on Lung Cancer (WCLC) 2022; August 6-9, 2022. Vienna, Austria. Abstract 2350.