DeLLphi-303 Study: Tarlatamab's Impact on Small Cell Lung Cancer

In an interview with Targeted Oncology, Kelly Paulson, MD, Swedish Cancer Institute Medical Oncology, discusses the key takeaways for oncologists from the phase 1b DeLLphi-303 study presented at the IASLC 2025 World Conference on Lung Cancer.

Paulson highlights critical takeaways from the DeLLphi-303 study, which evaluated the combination of tarlatamab (Imdelltra) with checkpoint inhibitors in patients with small cell lung cancer. The first key finding was the confirmed safety and tolerability of this dual immunotherapy approach. Paulson notes that this is a particularly important result because it aligns with observations from other cancer types, where combining immunotherapies has demonstrated greater efficacy than a single-agent approach. The successful safety profile of this combination in the DeLLphi-303 study is a crucial step forward for how clinicians might approach immunotherapy in this patient population. The fact that the combination was well-tolerated opens the door for its potential integration into the treatment paradigm.

The second major takeaway from the study was the unprecedented survival outcomes observed, particularly for patients who received the combined immunotherapy early in their treatment and continued with it as a maintenance therapy. Paulson expresses excitement about these findings, noting that the outcomes were dramatically better than what had been previously observed. While this was a phase 1b study involving 88 patients—a substantial group, though not a large-scale trial—the results were highly encouraging. These promising findings have already paved the way for a phase 3 study, known as DeLLphi-305, which is designed to further investigate the long-term survival benefits in a randomized, controlled setting. However, Paulson also acknowledges that the widespread availability of tarlatamab may lead to a lot of real-world crossover, which could affect the trial's findings.

Finally, the third and most immediately applicable takeaway from the study was the demonstration of ongoing benefit from treatment with tarlatamab even beyond initial disease progression. Paulson emphasizes this as a paradigm-shifting concept for clinicians. The data showed that 29 out of the 88 patients in the study were able to continue treatment beyond progression. The spider plots from the study, available in the supplement of The Lancet Oncology article, visually confirmed that many of these patients continued to experience an ongoing therapeutic benefit. This stands in stark contrast to the historical approach to treating small cell lung cancer, where a failing treatment would immediately prompt a switch to a new one. The DeLLphi-303 study suggests that, unlike traditional chemotherapies, immune-based treatments like tarlatamab should be approached differently, and that continued treatment may be a viable and beneficial option for some patients, even after initial signs of progression. This insight, according to Paulson, is something that clinicians can and should apply to their practices right away.

Watch more with Dr Paulson.

Read the full interview with Dr Paulson.