Tarlatamab Displays Overall Survival Benefit in Relapsed SCLC

Approval continuation of tarlatamab in relapsed SCLC may be contingent upon verification and description of clinical benefit in confirmatory trials, including the phase 3 DeLLphi-304 trial.

Tarlatamab-dlle (Imdelltra) significantly enhanced overall survival (OS) vs standard-of-care (SOC) chemotherapy in patients with small cell lung cancer (SCLC) who experienced disease progression on or following a single line of platinum-based chemotherapy in the phase 3 DeLLphi-304 trial (NCT05740566), according to a news release from the drug’s developer, Amgen.¹

The OS improvement marked the primary end point of the DELLphi-304 trial being met.

Currently, tarlatamab is approved in patients with extensive-stage SCLC (ES-SCLC) following progression on or after platinum-based chemotherapy under accelerated approval based on prior findings revealing enhanced response rate and duration of response. Approval continuation may be contingent upon verification and description of clinical benefit in confirmatory trials, including the phase 3 DeLLphi-304 trial.

The safety profile for tarlatamab was consistent with its known profile in patients with relapsed SCLC. DeLLphi-304 data will be presented at an upcoming medical congress.

"[SCLC] is one of the most aggressive malignancies, with a high unmet need for more effective therapies. The topline results from DeLLphi-304 demonstrate an overwhelming clinical benefit for [patients] living with this devastating disease and affirm [tarlatamab] as the standard of care," Jay Bradner, MD, executive vice president of Research and Development at Amgen, stated in the news release.¹ "We look forward to sharing these results with the scientific community and health authorities as we continue our efforts to bring [tarlatamab] to patients worldwide."

The phase 3 DeLLphi-304 trial randomly assigned patients to receive either tarlatamab or local SOC chemotherapy, which regionally included topotecan in all countries except Japan, lurbinectedin in the US, Canada, Australia, Singapore, and Korea, and amrubicin in Japan. Tarlatamab was received via intravenous infusion.

The primary end point was OS up to approximately 4 years.² Secondary end points included progression-free survival (PFS), change in quality-of-life score from baseline, overall response rate, disease control rate, duration of response, and safety.

Patients were eligible for enrollment if they were 18 years and older or legal adult age, whichever is older; had cytologically or histologically confirmed SCLC with progression or relapse demonstrated following 1 platinum-based chemotherapy regimen; had measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 within the 21-day screening period; had an ECOG performance status score of 0 or 1; and a minimum life expectancy of 12 weeks.

Those ineligible for enrollment had symptomatic central nervous system metastases; diagnosis or evidence of leptomeningeal disease, prior history of immune checkpoint inhibitors resulting in protocol-defined events; active autoimmune disease requiring systemic treatment within the past 2 years or other diseases requiring immunosuppressive therapy; a history of solid organ transplantation; or a history of other malignancy within the past 2 years.

Tarlatamab previously received priority reviewas a treatment for patients with ES-SCLC and progression following platinum-based chemotherapy in December 2023.³ Additionally, tarlatamab received accelerated approval in this indication based on data from the phase 2 DeLLphi-301 trial (NCT05060016) published in the New England Journal of Medicine in May 2024.^4,5

Topline data from the phase 2 trial revealed that among patients who received either 10 mg or 100 mg of tarlatamab, the ORR was 40.0% (97.5% CI, 29.1%-51.7%) and 31.8% (97.5% CI, 21.1%-44.1%), respectively. Additionally, the median OS was 14.3 months (95% CI, 10.8-not evaluable [NE]) and NE (95% CI, 12.4-NE) with respective doses, and the median PFS was 4.9 months (95% CI, 2.9-6.7) and 3.9 months (95% CI, 2.6-4.4). The most common treatment-emergent adverse effects (TRAEs) included cytokine release syndrome in 51.1% and 60.9% of respective groups.

References

1. Imdelltra® demonstrated superior overall survival in small cell lung cancer. News release. Amgen. April 11, 2025. Accessed April 14, 2025. https://tinyurl.com/33aay3u3
2. Study comparing tarlatamab with standard of care chemotherapy in relapsed small cell lung cancer (DeLLphi-304). ClinicalTrials.gov. Updated August 28, 2024. Accessed April 14, 2025. https://tinyurl.com/4pr74jmr
3. FDA grants priority review to Amgen's tarlatamab application for advanced small cell lung cancer. News release. Amgen. December 13, 2023. Accessed April 14, 2025. https://prn.to/47X7yu7
4. FDA grants accelerated approval to tarlatamab-dlle for extensive stage small cell lung cancer. News release. FDA. May 16, 2024. Accessed April 14, 2025. https://tinyurl.com/48k34rw5
5. Ahn MJ, Cho BC, Felip E, et al. Tarlatamab for patients with previously treated small-cell lung cancer. N Engl J Med. 2023;389:2063-2075. doi:10.1056/NEJMoa2307980