Phase 3 IMforte Trial Meets Primary Endpoints of OS and PFS in Extensive-Stage SCLC

The phase 3 IMforte trial has met its primary endpoints of overall survival (OS) and progression-free survival (PFS), demonstrating a “clinically meaningful benefit” of lurbinectedin plus atezolizumab as first-line maintenance treatment in patients with extensive-stage small cell lung cancer (ES-SCLC), according to the study investigators.

The study, which evaluated lurbinectedin plus atezolizumab as first-line maintenance treatment in patients with ES-SCLC, will be presented at the upcoming 2025 American Society of Clinical Oncology (ASCO) Annual Meeting by lead study author Luis G. Paz Ares, MD, PhD, of the 12 de Octubre University Hospital in Madrid, Spain.

“While the introduction of immunotherapy in first-line treatment has improved outcomes, advanced small cell lung cancer remains difficult to treat,” Dr. Paz Ares said in a statement provided by ASCO. “The phase 3 IMforte trial shows that the new treatment combination of lurbinectedin and atezolizumab given as maintenance therapy after first-line treatment helps people live longer and reduces the risk of disease progression or death. This outcome represents a major milestone and could provide a much-needed option for advancing the treatment of this aggressive disease.”

Lung Cancers Today Editorial Board Member Stephen Liu, MD, explained why he’s looking forward to the full presentation of IMforte data, which will take place at 5 p.m. CT on Monday, June 2.

“We’ll see the full data set and see how this could inform practice for patients with small cell lung cancer,” Dr. Liu told Lung Cancers Today. “This is an important strategy because as we know, 50% of people never receive second-line treatment.”

The IMforte trial included 660 patients with treatment-naïve ES-SCLC who had no history of metastases to the brain or spinal cord, and a good performance status.

All patients enrolled in the study received standard-of-care induction therapy of atezolizumab, carboplatin, and etoposide in four 21-cycles. Following induction therapy, eligible patients without disease progression were able to continue in the study if they had an ongoing tumor response or stable disease after four cycles. Study investigators randomly assigned patients 1:1 to receive lurbinectedin and atezolizumab (n=242) or atezolizumab alone (n=241) until disease progression, unacceptable toxicity, or withdrawal.

The participants were from 91 study sites in 13 different countries. Around 82% were White, 13% were Asian, 7% were Hispanic or Latino, and 5% had another racial origin. The median age of the participants was 66 years, and approximately 63% of the patients were men.

The researchers stratified patients by liver metastases at induction baseline, receipt of prophylactic cranial irradiation before randomization, performance status, and LDH at maintenance baseline. Crossover was not allowed in the phase 3 IMFORTE trial. The primary endpoints were independent review facility (IRF)–assessed PFS and OS assessed from randomization into the maintenance phase.

With a median follow-up of 15 months, the median progression-free survival (PFS) was 5.4 months in the patients receiving lurbinectedin and atezolizumab arm versus 2.1 months in those receiving atezolizumab alone. In addition, those who received the combination treatment had a 46% lower risk for cancer progression than those who received atezolizumab alone.

The median overall survival was 13.2 months for patients receiving lurbinectedin plus atezolizumab, compared to 10.6 months for patients receiving atezolizumab alone. In addition, those who received the combination treatment had a 27% lower risk for death than those who received atezolizumab alone.

Charu Aggarwal, MD, MPH, FASCO, Leslye M Heisler Professor of Lung Cancer Excellence at University of Pennsylvania – Abramson Cancer Center, and an ASCO Expert in lung cancer, weighed in on the findings in a statement provided by ASCO.

“Immunotherapy has improved survival outcomes for patients with extensive-stage small cell lung cancer (ES-SCLC), marking meaningful progress in a historically challenging disease. However, despite these advances, long-term outcomes remain suboptimal, underscoring the need for better strategies,” Dr. Aggarwal said. “The integration of lurbinectedin—a novel DNA-damaging agent—into the maintenance setting alongside atezolizumab following initial chemo-immunotherapy represents an important next step. This approach offers a way to extend disease control and may signal a shift toward more durable benefit[s] for patients.”

The median treatment duration was 4.1 months on lurbinectedin and 4.2 months on atezolizumab in the patients receiving the combination treatment, while it was 2.1 months in those receiving atezolizumab alone.

However, there was “a noted difference in adverse events between the two groups,” officials said in a press release about the findings, explaining that treatment-related adverse events occurred in 83.5% of patients receiving the combination treatment, compared to 40% of those receiving atezolizumab alone.

Grade 3 or grade 4 adverse events were reported in around one-quarter (25.6%) of patients receiving the combination treatment, with a grade 5 adverse event occurring in 0.8%. Among those receiving atezolizumab alone, grade 3 or 4 adverse events occurred in 5.8%, with a grade 5 adverse event occurring in 0.4%. Among patients receiving lurbinectedin and atezolizumab, 6.2% stopped treatment due to side effects compared to 3.3% of those receiving atezolizumab alone.

Based on these findings, the study investigators concluded that the combination treatment was “generally well tolerated, with no new or unexpected safety signals.” They emphasized that IMforte “is the first global Phase 3 study to show PFS and OS improvement, “first-line maintence treatment for ES-SCLC, and “supports maintenance [lurbinectedin plus atezolizumab] as a new option for [patients] with this aggressive disease.”