The phase 3 EMERGE-201 for patients with advanced urothelial carcinoma, large cell neuroendocrine carcinoma of the lung, or homologous recombination deficient has begun.
Enrollment has begun in the phase 3 EMERGE-201 study of patients with advanced urothelial carcinoma, large cell neuroendocrine carcinoma of the lung, or homologous recombination deficient (HRD) tumors who have progressed on a platinum-containing regimen, according to an announcement by Jazz Pharmaceuticals.1
With the first patient now enrolled, the phase 2, multicenter, open-label study (NCT05126433) will explore treatment with single-agent lurbinectedin (Zepzelca) with a primary end point of objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST).2
"Even with the rapid advancements in medical technology and care delivery across many tumor types over the last decade, there still remain many patients who continue to face unmet needs and experience a high burden of morbidity and mortality," said Arielle Heeke, MD, breast medical oncologist at the Levine Cancer Institute and a primary investigator in the EMERGE-201 trial, in a press release.1 "With the EMERGE-201 trial now underway, we look forward to seeing the potential clinical impact of Zepzelca on advanced solid tumor cancers, including HRD cancers, that have limited approved treatment options other than traditional chemotherapy. The trial will evaluate if this treatment can elicit tumor response based upon the underlying biology of these cancers and Zepzelca's novel method of action."
In addition to ORR, EMERGE-201 is also evaluating investigator-assessed progression-free survival, time to response, duration of response, disease control rate, and overall survival as secondary end points.2
In all 3 disease cohorts, lurbinectedin will be administered at 3.2 mg/m2 by intravenous infusion every 3 weeks and continued until disease progression, withdrawal of patient consent, patient lost to follow-up, or unacceptable toxicity. Additionally, the study or individual cohort may be terminated by the sponsor for lack of efficacy signal or any other reason.
To be eligible for the study, patients must be 18 years or age or older with an ECOG performance status of 0 or 1, adequate organ and bone marrow function, measurable disease per RECIST v1.1, and have advanced urothelial carcinoma, large cell neuroendocrine carcinoma of the lung, or HRD tumor. Once enrolled, patients are required to use adequate contraception.
The study excludes patients who were previously treated with trabectedin or lurbinectedin within 4 weeks of study enrollment, a live vaccine within 4 weeks of the first dose of lurbinectedin, or prior allogeneic bone marrow and solid organ transplant. The study also excluded individuals based on disease history and present comorbidities including symptomatic central nervous system metastasis requiring steroids, clinical significant cardiovascular disease, active infection requiring systemic therapy, significant non-neoplastic liver disease, positive hepatitis V or C infection at screening, and positive human immunodeficiency virus infection at screening.
EMERGE-201 is recruiting patients who meet the study requirements at centers in Connecticut, New York, Pennsylvania, and South Carolina. Evidentially, 20 sites in the United States will participate in the trial.
"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, MD, MSCE, executive vice president, global head of research and development of Jazz Pharmaceuticals., in the press release.1 "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."
1. Jazz Pharmaceuticals announces first patient enrolled in EMERGE-201 phase 2 basket trial evaluating Zepzelca® (lurbinectedin) monotherapy in patients with select advanced or metastatic solid tumors. News release. March 24, 2022. Accessed March 24, 2022. https://prn.to/3tzHgMU
2. Lurbinectedin monotherapy in participants with advanced or metastatic solid tumors (EMERGE-201). Clincialtrials.gov. Updated March 24, 2022. Accessed March 24, 2022.