IMforte and DeLLphi-304: Dr. Stephen Liu Unpacks New Data in SCLC

Stephen Liu, MD, director of Thoracic Oncology at Georgetown University, joined Lung Cancers Today to discuss key developments in small cell lung cancer (SCLC) treatment from the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

“At ASCO 2025, we saw some major updates in small cell lung cancer, with two phase 3 trials meeting their primary end point and changing the standard of care,” Dr. Liu explained.

These two phase 3 trials were the IMforte trial, presented by Luis G. Paz-Ares, MD, PhD, of the Hospital Universitario 12 de Octubre, and the phase 3 DeLLphi-304 trial, presented by Charles M. Rudin, MD, PhD, of the Memorial Sloan Kettering Cancer Center.

The phase 3 IMforte trial evaluated lurbinectedin plus atezolizumab as first-line maintenance treatment for patients with extensive-stage SCLC, meeting its primary end points of overall survival (OS) and progression-free survival (PFS).

“A maintenance strategy introducing treatment earlier is a proactive one, rather than reacting to the relapse,” Dr. Liu explained. “But despite how logical a maintenance approach is, there’s never been a positive maintenance trial until this one.”

The median OS was 13.2 months for patients receiving lurbinectedin plus atezolizumab, compared with 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.

With a median follow-up of 15 months, the median PFS was 5.4 months in the patients receiving lurbinectedin and atezolizumab 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.

However, it’s important to recognize that “most patients do relapse and are in need of second-line therapy at progression,” Dr. Liu said.

The historical standard for second-line treatment has been chemotherapy, but the DeLLphi-304 study of tarlatamab versus chemotherapy in patients with SCLC who have had progression during or after platinum-based chemotherapy has “redefined that second-line option,” he said.

The DeLLphi-304 study results showed that patients receiving tarlatamab had a median OS of 13.6 months, which was significantly longer than the median OS of 8.3 months in those receiving chemotherapy (hazard ratio [HR], 0.60; 95% CI, 0.47-0.77; P<0.001).

“The OS hazard ratio of 0.60 is unrefutable,” Dr. Liu said. “This becomes our second-line option when available to patients.”

The median PFS was 4.2 months in those receiving tarlatamab, significantly longer than the median PFS of 3.2 months in those receiving chemotherapy (HR, 0.72; 95% CI, 0.59-0.88; P<0.001).

Dr. Liu concluded by reflecting on how these two studies are shaping standards of care and the treatment landscape.

“Our standard of care, in my opinion, for small cell lung cancer would be chemotherapy plus a PD-L1 inhibitor and then maintenance lurbinectedin plus atezolizumab; for those who do relapse, in the second-line setting, tarlatamab,” Dr. Liu said. “We have more agents to come: antibody-drug conjugates, trispecific T-cell engagers. The field continues to be redefined for the new standard of care after ASCO 2025.”