Zepzelca Plus Tecentriq Significantly Improves Survival in Extensive-Stage Small Cell Lung Cancer

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The combination of Zepzelca (lurbinectedin; Jazz Pharmaceuticals) with Tecentriq (atezolizumab; Roche) produced significant improvements in overall survival (OS) and progression-free survival (PFS) in patients with extensive-stage small cell lung cancer (ES-SCLC) compared to Tecentriq alone as a maintenance therapy following induction treatment, according to preliminary data from the Phase III IMforte trial (NCT05091567).^1,2 Zepzelca was previously granted accelerated approval by the FDA in June 2020 for the treatment of adults with metastatic SCLC who experienced disease progression on or following platinum-based chemotherapy.³

"Each year, approximately 30,000 new cases of small cell lung cancer (SCLC) are reported in the US. A majority of these patients are diagnosed with extensive stage disease, which is aggressive and often difficult to treat, with poor prognosis," IMforte trial principal investigator Luis Paz-Ares, MD, PhD, head of medical oncology at the Hospital Universitario 12 de Octubre in Madrid, Spain, said in a press release. "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."¹

Zepzelca is an alkylating medication that binds to guanine residues within DNA, which triggers a response that can impact the activity of DNA-binding proteins, including some transcription factors and DNA repair pathways, to cause a disruption of the cell cycle and eventual cell death.

The ongoing, randomized, multicenter IMforte maintenance trial is comparing the efficacy, safety, and pharmacokinetics of Zepzelca combined with Tecentriq vs. standard-of-care first-line maintenance with Tecentriq monotherapy following induction treatment with carboplatin, etoposide, and Tecentriq in adult patients aged 18 years and above with ES-SCLC. The trial’s primary endpoints are OS and PFS as assessed by independent review facility.

The trial includes both an induction phase and a maintenance phase. For patients to be considered for eligibility screening to enter the maintenance phase, requirements included having ongoing response or stable disease as per RECIST v1.1 criteria following the induction phase comprised of four cycles of carboplatin, etoposide, and Tecentriq. Those eligible for the maintenance phase were randomly assigned in a 1:1 ratio to receive either Zepzelca plus Tecentriq or Tecentriq monotherapy.

The results showed a statistically significant improvement for the primary endpoints of OS and independent review facility-assessed PFS compared to Tecentriq monotherapy.

In terms of safety, no new signals were reported with the Zepzelca plus Tecentriq combination, which was well-tolerated and consistent with the previously established safety profiles for both drugs, according to the investigators. The most common adverse events associated with Zepzelca in prior trials (≥20%) include laboratory abnormalities; leukopenia; lymphopenia; fatigue; anemia; neutropenia; elevated creatinine; elevated alanine aminotransferase; elevated glucose; thrombocytopenia; nausea; reduced appetite; musculoskeletal pain; reduced albumin; constipation; dyspnea; reduced sodium; elevated aspartate aminotransferase; vomiting; cough; reduced magnesium; and diarrhea.³

Jazz and Roche stated they will submit deeper data from the trial for presentation at a future medical meeting. Jazz stated it will submit a supplemental New Drug Application to the FDA in first half of 2025 for the combination as a first-line maintenance treatment for ES-SCLC.

"The results of the Phase III IMforte trial are highly encouraging and showed a statistically significant benefit for the Zepzelca and atezolizumab combination for extensive-stage small cell lung cancer patients 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, Jazz Pharmaceuticals executive vice president, global head of research and development, and chief medical officer, said in a press release."¹

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://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?intr=NCT05091567&rank=1

3. Jazz Pharmaceuticals Announces U.S. FDA Accelerated Approval of Zepzelca™ (lurbinectedin) for the Treatment of Metastatic Small Cell Lung Cancer. Jazz Pharmaceuticals; June 15, 2020. Accessed October 15, 2024. https://www.prnewswire.com/news-releases/jazz-pharmaceuticals-announces-us-fda-accelerated-approval-of-zepzelca-lurbinectedin-for-the-treatment-of-metastatic-small-cell-lung-cancer-301077082.html