On December 4, 2024, the FDA announced two significant approvals in lung cancer treatment, including zenocutuzumab-zbco for non-small cell lung cancer (NSCLC) and durvalumab for limited-stage small cell lung cancer (SCLC), marking significant advances in the fight against both diseases.
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Zenocutuzumab for NRG1 Fusion-Positive NSCLC
The first approval granted was for zenocutuzumab-zbco, a HER2xHER3 bispecific antibodypy developed for adults with advanced, unresectable, or metastatic NSCLC harboring an neuregulin 1 (NRG1) gene fusion. This decision is the first FDA approval for a systemic therapy targeting NRG1 fusions, a rare and challenging genetic driver in lung cancer.
The approval is based on results from the eNRGy study, a multicenter, open-label trial evaluating patients with advanced or metastatic NRG1 fusion-positive cancers who had disease progression after prior therapies. Among the 64 patients with NSCLC, the study demonstrated an overall response rate (ORR) of 33% and a median duration of response (DOR) of 7.4 months. While adverse effects were observed, including diarrhea, fatigue, musculoskeletal pain, and nausea, the approval underscores the growing potential of precision oncology to improve outcomes for patients with rare genetic alterations.
At the same time, the FDA approved zenocutuzumab-zbco for advanced, unresectable, or metastatic pancreatic adenocarcinoma patients also harboring a NRG1 gene fusion with disease progression on or after prior systemic therapy.
Durvalumab for Limited-Stage SCLC
The FDA also approved durvalumab for adults with limited-stage small cell lung cancer (LS-SCLC) whose disease had not progressed following concurrent platinum-based chemotherapy and radiation therapy. This approval is based on data from the ADRIATIC trial, a randomized, double-blind, placebo-controlled study that evaluated the efficacy of durvalumab in extending survival for LS-SCLC patients.
Results showed that durvalumab significantly improved overall survival (OS), with a median OS of 55.9 months compared to 33.4 months for placebo. Progression-free survival (PFS) also improved, with a median of 16.6 months in the durvalumab group versus 9.2 months in the placebo group. Finally, the most common adverse effects included pneumonitis or radiation pneumonitis and fatigue, consistent with its known safety profile.
These approvals represent major steps forward in the treatment landscape for lung cancer. For NSCLC patients with rare NRG1 gene fusions, zenocutuzumab offers the first targeted systemic therapy addressing this genetic driver. Meanwhile, durvalumab’s demonstrated survival benefits bring new hope to those with limited-stage SCLC, emphasizing the transformative impact of immunotherapy.
References:
“FDA grants accelerated approval to zenocutuzumab-zbco for non-small cell lung cancer and pancreatic adenocarcinoma,” U.S. Food And Drug Administration, Dec. 04, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zenocutuzumab-zbco-non-small-cell-lung-cancer-and-pancreatic
A. M. Schram et al., “Efficacy and safety of zenocutuzumab, a HER2 x HER3 bispecific antibody, across advanced NRG1 fusion (NRG1+) cancers.,” Journal of Clinical Oncology, vol. 40, no. 16_suppl, p. 105, Jun. 2022, doi: 10.1200/jco.2022.40.16_suppl.105.
“FDA approves durvalumab for limited-stage small cell lung cancer,” U.S. Food And Drug Administration, Dec. 04, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-limited-stage-small-cell-lung-cancer
Y. Cheng et al., “Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer,” New England Journal of Medicine, vol. 391, no. 14, pp. 1313–1327, Sep. 2024, doi: 10.1056/nejmoa2404873.
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