The Phase II trial is evaluating zepzelca as a monotherapy in patients with urothelial carcinoma, large cell neuroendocrine carcinoma of the lung and HRD tumors.
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Jazz Pharmaceuticals announced that the first patient in its EMERGE-201 Phase II clinical trial has been dosed. The trial is evaluating the therapeutic zepzelca (lurbinectedin) as a monotherapy in patients with urothelial carcinoma, large cell neuroendocrine carcinoma of the lung and homologous recombination deficient (HRD) tumors.
In June 2020, the U.S. Food and Drug Administration granted accelerated approval to zepzelca for the treatment of adult patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy. The approval was based on efficacy results from a clinical trial showcasing that the drug produced an overall response rate of 35% with a median duration of about 5 months in the 105 patients studied. Full approval for the drug in this oncological group may be granted after the conclusion of Jazz’s Phase III clinical trial titled LAGOON, initiated in December 2021.
Now, Jazz is looking to broaden the therapeutic horizons for zepzelca in several other oncological indications which represent patients with unmet needs with high burdens of morbidity and mortality. The EMERGE-201 Phase II trial is designed to assess the safety and efficacy of zepzelca in patients with solid tumors with diagnoses including urothelial carcinoma, neuroendocrine carcinoma of the lung and HRD tumors.
Patients enrolled in the trial will receive an intravenous dose of the drug on day one of an every-three-week dosing cycle. Primary endpoints of the test include disease control rate, time-to-response and overall survival.
Zepzelca is effective in controlling proliferative malignant cells because it is an alkylating drug that binds guanine receptors within DNA. By binding to these receptors, zepzelca can trigger a cascade of events that impact DNA binding proteins that disrupt the cell cycle in malignant cells, eventually causing cell death.
“This trial initiation is an exciting milestone for Zepzelca’s clinical development program, as we seek to evaluate its clinical utility beyond treating small cell lung cancer,” said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. “Given Zepzelca triggers a cascade of events that can affect the activity of DNA binding proteins – including transcription factors and DNA repair pathways – we look forward to analyzing Zepzelca’s activity in additional difficult-to-treat cancers where driver oncogenes are actively transcribed and DNA repair mechanisms are inefficient, such as urothelial carcinoma, large cell neuroendocrine carcinoma of the lung and HRD-positive tumors.”
Results from zepzelca clinical trials will be highly anticipated by those with urothelial carcinoma and large cell neuroendocrine carcinoma. Urothelial carcinoma is the fourth most common tumor type in the U.S., is highly aggressive and can be difficult to treat if it becomes more advanced. Progressive disease after chemotherapy is characterized by a short survival, leaving patients with limited options. Large cell neuroendocrine carcinoma is a rare type of cancer occurring in the lungs and colon, which currently has no standard care due to limited clinical research making it a high priority for oncological therapies.
Following its accelerated approval in June 2020, the National Comprehensive Cancer Network added zepzelca to its Clinical Practice Guidelines in Oncology for small cell lung cancer. In November 2021, zepzelca became the first new treatment for Stage III or metastatic small lung cell cancer in more than a decade when it reached commercial availability in Canada.
