Lurbinectedin/Atezolizumab Combination Improves Survival in ES-SCLC

Lurbinectedin (Zepzelca) plus atezolizumab (Tecentriq) produced statistically significant overall survival (OS) and progression-free survival (PFS) benefits vs atezolizumab monotherapy when used as frontline maintenance therapy in adult patients with extensive-stage small cell lung cancer (ES-SCLC) who had received induction therapy with carboplatin, etoposide, and atezolizumab, according to topline findings from the ongoing phase 3 IMforte trial (NCT05091567).¹

The combination was generally well tolerated, according to a news release from Jazz Pharmaceuticals, the developer of lurbinectedin. The release noted that the preliminary safety data from IMforte were consistent with the known safety profiles of lurbinectedin and atezolizumab, and no new safety signals were reported in the combination arm of the trial.

Jazz Pharmaceuticals and Roche, the developer of atezolizumab, plan to submit the topline data from IMforte for presentation at an upcoming medical meeting.

“Each year, approximately 30,000 new cases of SCLC are reported in the United States [US]. A majority of these patients are diagnosed with extensive-stage disease, which is aggressive and often difficult to treat, with poor prognosis,” Luis Paz-Ares, MD, PhD, chair of the Medical Oncology Department at the Hospital 12 de Octubre in Madrid, Spain, and the principal investigator of IMforte, stated in the news release. “These trial results demonstrate the efficacy of lurbinectedin, the most widely used agent in second-line SCLC in the US, in combination with standard-of-care atezolizumab for patients in first-line maintenance treatment, a much-needed advancement for patients with extensive disease.”

The randomized, multicenter IMforte trial is enrolling patients at least 18 years of age with histologically or cytologically confirmed ES-SCLC.² The trial consists of 2 phases: an induction phase and a maintenance phase. To be eligible for the induction phase, patients need to have an ECOG performance status (PS) of 0 or 1; be naive to prior therapy for ES-SCLC; be treatment free for at least 6 months since the last dose of chemotherapy or radiotherapy for limited-stage LSCLC; have adequate hematologic and end-organ function to receive 4 cycles of induction therapy with carboplatin, etoposide, and atezolizumab; and have measurable disease per RECIST 1.1 criteria.

To be eligible for the maintenance phase of the trial, patients need to have an ECOG PS of 0 or 1, an ongoing response or stable disease per RECIST 1.1 criteria following the induction phase of the trial, and adequate hematologic and end-organ function.

In the induction phase, patients are receiving 4 cycles of carboplatin, etoposide, and atezolizumab. Atezolizumab is administered at 1200 mg on day 1 of each 21-day cycle in combination with a standard dose of carboplatin on day 1 of each cycle and a standard dose of etoposide on days 1, 2, and 3 of each cycle. In the maintenance phase, patients are randomly assigned 1:1 to receive either lurbinectedin plus atezolizumab or atezolizumab monotherapy. Atezolizumab is administered at the same dose and schedule as in the induction phase. Lurbinectedin is administered at 3.2 mg/m2 on day 1 of each 21-day cycle.

OS and independent review facility–assessed PFS serve as the trial’s primary end points. Key secondary end points include investigator-assessed PFS, ORR, DOR, and safety.

“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. These results demonstrate the potential of this regimen to delay disease progression and extend survival for patients with this aggressive disease," Rob Iannone, MD, MSCE, executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals, added in the news release.¹ “We are pleased with these clinically meaningful results and plan to submit a supplemental new drug application 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.”

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 plc. October 15, 2024. Accessed October 15, 2024. https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-announces-statistically-significant-overall
2. A phase III, open-label study of maintenance lurbinectedin in combination with atezolizumab compared with atezolizumab in participants with extensive-stage small-cell lung cancer (IMforte). ClinicalTrials.gov. Updated October 8, 2024. Accessed October 15, 2024. https://clinicaltrials.gov/study/NCT05091567