Phase 3 Investigation of Lurbinectedin Plus Atezolizumab Underway in ES-SCLC

Luis Paz-Ares, MD, PhD

A clinical trial of the frontline combination of lurbinectedin (Zepzelca) and atezolizumab (Tecentriq) for the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) has enrolled its first subject, according to a press release by Jazz Pharmaceuticals.¹

"Small cell lung cancer can progress faster than most forms of lung cancer, although new treatment options can prolong life and improve long-term care options," said Luis Paz-Ares, MD, PhD, professor of medicine at Hospital Universitario 12 de Octubre in Madrid, Spain. "Jazz's collaborative research with Roche will provide much-needed insights into a potentially new small cell lung cancer therapeutic option in the first-line setting. With approximately a quarter million patients diagnosed globally with small cell lung cancer each year–including thousands in the [United States] alone–a new first-line maintenance combination treatment would be a welcome advancement for patients with extensive disease."

In the phase 3, randomized, open-label, multicenter IMforte study (NCT05091567), the coprimary end points are progression-free (PFS) and overall survival (OS). The secondary outcomes include investigator assessed PFS, confirmed objective response rate, duration of response, PFS rates at 12 and 24 months, OS rates at 12 and 24 months, the percentage of patients with adverse events, the percentage of patients with anti-drug antibodies, and the time to confirmed deterioration.²

To evaluate these end points, 600 patients will be enrolled to the study. In the experimental arm, patients will be treated with atezolizumab at a fixed dose of 1200 mg on day 1 of each 21-day cycle for 4 cycles in the induction phase. In the maintenance phase, atezolizumab treatment will also be a fixed dose of 1200 mg on day 1 of each 21-day cycle. Lurbinectedin in a 3.2 mg/m2 dose will be administered by intravenous infusion on day 1 of each 21-day cycle during the maintenance phase, and both carboplatin and etoposide will be administered as induction therapy.

In the comparator arm, patients with ES-SCLC will be treated with matching doses of atezolizumab induction and maintenance therapy as well as carboplatin and etoposide maintenance.

Patients are eligible to enroll in the induction phase of the study given they have an ECOG performance status of 0 or 1, have not received prior systemic therapy for ES-SCLC, have been treatment free for at least 6 months, have histologically or cytologically confirmed disease, have adequate hematologic and end-organ function, show measurable disease per RECIST v1.1, and are negative for HIV, and hepatitis B or C at the time of screening.

The study excludes patients who present with central nervous system metastases, have active or previous autoimmune disease, have a history of another malignancy within 5 years, or who show pulmonary diseases on CT scan.

Select patients with ES-SCLC may be able to continue to maintenance therapy including those with ongoing response or stable disease, resolved of grade 1 toxicities, and adequate hematologic and end-organ function.

"We've already witnessed strong clinical demand for Zepzelca as a therapy for metastatic small cell lung cancer patients in the second-line setting," said Rob Iannone, MD, MSCE, executive vice president, research and development, and chief medical officer at Jazz Pharmaceuticals, in the press release.¹ "This collaboration with Roche marks an opportunity to further study Zepzelca's safety and efficacy in combination with the PD-L1 inhibitor, Tecentriq, in a pivotal phase 3 clinical trial, as part of a first-line, standard-of-care, immunotherapy treatment option for patients with extensive-stage small cell lung cancer, a devastating disease for which novel treatments and strategies are needed."

_References:

_{1. Jazz Pharmaceuticals Announces first patient enrolled in IMforte phase 3 trial evaluating Zepzelca® (lurbinectedin) in combination with a PD-L1 inhibitor in small cell lung cancer. News release. Jazz Pharmaceuticals. December 1, 2021. Accessed December 1, 2021. https://bit.ly/3xH6d9w}

_{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. Accessed December 1, 2021.}