Recent SCLC Data May Impact How Patients Are Treated Day-to-Day

Various trials within the small cell lung cancer space were brought to light following recent data, impacting how patients will be treated in the future.

Various trials within the small cell lung cancer (SCLC) space were brought to light following data read outs for physicians at the 2025 ASCO Annual Meeting, ultimately impacting how patients will be treated in the near future.

Dr. Joshua K. Sabari sat down to interview Dr. Prantesh Jain on this topic, highlighting impactful trials such as the DELPHI-304 study, the IMforte trial, and more within the treatment space.

“SCLC is such a recalcitrant disease, so it's exciting to see so many hopeful therapeutic options now available,” Sabari emphasized in the interview with Jain.

To hear Dr. Sabari and Dr. Jain’s conversation on non-small cell lung cancer (NSCLC), be sure to watch more here!

Sabari is the editor in chief of CURE. He also serves as an assistant professor in the Department of Medicine at NYU Grossman School of Medicine and director of High Reliability Organization Initiatives at Perlmutter Cancer Center.

Moreover, Jain is a medical oncologist at Roswell Park Comprehensive Cancer Center, in Buffalo, New York, where he also serves as an assistant professor of Oncology in the Department of Medicine. He also works at the State University of New York at Buffalo as a clinical assistant professor.

Sabari: Hello. I'm Dr. Joshua K. Sabari, a thoracic medical oncologist at NYU Langone Health Perlmutter Cancer Center, in New York, and I'm also the editor in chief of CURE. I'm really excited today to be joined by Dr. Jain, a thoracic medical oncologist.

Dr. Jain, please introduce yourself.

Jain: Hi, thanks for having me. I'm Dr. Prantesh Jain, a thoracic oncologist at Roswell Park Cancer Center, and I'm excited to be here to share updates in lung cancer from ASCO this year.

Sabari: Thank you for joining us, and thank you to our readers and listeners for joining in today. Tell us, what was exciting to you at ASCO 2025? What should our readers to take away in the lung cancer space? There were so many exciting presentations, so I'll turn it to you.

Jain: There were a lot of exciting studies. A few that stood out for me were a couple of studies in the SCLC space, including the DELPHI-304 study. In NSCLC, the RESILIENT-1 study, NeoADAURA trial, and a five-year update on the CheckMate 816 study. I am excited to, you know, talk about that more.

Sabari: So, let's walk through those. SCLC is a very rare disease, with about 30,000 cases a year in the United States; it is also quite an aggressive disease. We know standard of care has been chemotherapy and immunotherapy in newly diagnosed patients.

Let's walk through some of the data that excited you in the SCLC space.

Jain: SCLC continues to pose a significant challenge due to its rapid progression and the limited availability of effective second-line therapies. Notably, nearly 60% of these patients never reach second-line treatment because of rapid clinical deterioration.

The phase 3 IMforte trial enrolled 483 patients with extensive-stage SCLC to investigate whether the addition of Zepzelca (lurbinectedin) to Tecentriq (atezolizumab) in the first-line maintenance setting provides a survival benefit compared to Tecentriq alone. Patients who achieved stable disease, partial response, or complete response after induction chemo-immunotherapy with carboplatin, etoposide, and Tecentriq were included. Patients with CNS metastasis were excluded. Approximately 3.2 months after induction, patients were randomized to receive maintenance therapy with either Zepzelca plus Tecentriq or Tecentriq alone. The primary endpoints were progression-free survival and overall survival, measured from the maintenance randomization.

Key results showed a significantly prolonged median progression-free survival with the combination arm at 5.4 months, compared to 2.1 months for the Tecentriq-alone arm… indicating both clinical and statistical significance. Median overall survival also improved to 13.2 months from 10.6 months. Furthermore, the 12-month overall survival rates increased from 44% to 56% in the patient population receiving the combination therapy.

The confirmed objective response rate, measured from baseline after induction chemo-immunotherapy, nearly doubled from 10.4% in the Tecentriq-alone arm to 19.4% in the experimental arm. Toxicities were consistent with what would be expected from the combination of Zepzelca and immunotherapy, primarily being hematologic and more frequent in the combination arm, but manageable with appropriate supportive care.

In terms of clinical implications, I believe this study is practice-changing. It is the first phase 3 trial to demonstrate a clear survival benefit in the first-line maintenance setting for extensive-stage SCLC. This study was presented by Dr. Luis Paz-Ares at ASCO this year. I feel that this will become the new standard of care, moving Zepzelca from the second-line to the first-line setting. It will be interesting to see how the efficacy balances with the toxicity, and to explore the optimal sequencing with other emerging agents like Imdelltra (tarlatamab-dlle).

Sabari: I couldn't agree more. In those who are diagnosed with extensive stage SCLC who start with chemotherapy and immunotherapy, this was practice changing data. But, as you mentioned, it is the first study to be positive in the first line maintenance setting after four cycles of chemo and immunotherapy. I agree with you, there is real rationale now to add Zepzelca, a novel chemotherapy, to the Tecentriq, a PD-L1 inhibitor.

You mentioned the second-line setting. We also saw very exciting data from the DELPHI-304 study of Imdelltra. Tell us a little bit about Imdelltra, and what those results were. Why are they so practice-changing in the second line setting?

Jain: The DELPHI-304 is a phase 3 randomized controlled trial that built upon the initial promising results from the DELPHI-301 study. It tests Imdelltra, a novel bispecific T-cell engager that targets DLL3. DLL3 is an aberrantly expressed protein found in 85% to 90% of SCLC tumors. The drug essentially redirects cytotoxic T cells to create an immunologic synapse to kill DLL3-positive cancer cells.

To briefly describe the study, it's an open-label, randomized phase 3 trial that compared the efficacy of Imdelltra in the second-line setting against a physician's choice chemotherapy, which included either topotecan, amrubicin, or Zepzelca. These patients had received at least one prior line of platinum-based chemotherapy, with or without an anti-PDL1 inhibitor. Patients enrolled had a PS (performance status) of 0 to 1, and the study also included patients with asymptomatic brain metastases. The study randomized the groups in a 1:1 fashion to receive either Imdelltra or investigator's choice chemotherapy.

The results in the second-line setting were very significant. The median overall survival was 13.6 months with Imdelltra versus 8.3 months with chemotherapy, resulting in a hazard ratio of 0.60, indicating a 40% risk reduction with a P-value less than 0.001. This was both clinically and statistically significant. The median progression-free survival was 4.2 months versus 3.7 months, with a hazard ratio of 0.71. The overall objective response rate doubled to 35% versus 20% in the control arm. The duration of response was longer with Imdelltra, at 6.9 months versus 5.5 months with chemotherapy, with nearly half of the responders ongoing at the data cutoff.

Importantly, patient-reported outcomes favored Imdelltra, showing significant improvement in dyspnea and cough, which are common symptoms SCLC patients face as the disease progresses and grows, especially centrally. Even the safety profile was manageable, with grade 3 or greater treatment-related adverse events being lower in the Imdelltra arm (27% versus 62% in the chemotherapy arm). Furthermore, adverse events of interest, such as cytokine release syndrome, occurred in 60% of patients but were mostly grade 1 or 2. Crucially, immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in only 6% of patients, and all cases were grade 1 or 2.

In terms of clinical implications for the study, it's the first phase 3 trial demonstrating an overall survival benefit with this novel DLL3 T-cell engager. It represents a practice-changing option in the second-line setting for our patients.

Sabari: I couldn't agree more. As you mentioned, SCLC is such a recalcitrant disease, so it's exciting to see so many hopeful therapeutic options now available. Imdelltra currently has an accelerated approval in the second line. I am sure we'll see a confirmed, full approval based on this very impressive phase 3 study.

Transcript has been edited for clarity and conciseness.

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