Tarlatamab Yields OS Improvement in SCLC After Platinum Progression

Tarlatamab in SCLC After Platinum Progression

| Image Credit: © Sebastian Kaulitzki – stock.adobe.com

Treatment with tarlatamab-dlle (Imdelltra) led to a statistically significant and clinically meaningful improvement in overall survival (OS) vs standard-of-care (SOC) chemotherapy in patients with small cell lung cancer (SCLC) whose disease progressed on or after 1 line of platinum-based chemotherapy, meeting the primary end point of the phase 3 DeLLphi-304 trial (NCT05740566).1

Safety data for tarlatamab were consistent with the known profile of the DLL3- and CD3-directed bispecific antibody.

Full data from DeLLphi-304 will be presented at an upcoming medical conference.

"SCLC is one of the most aggressive malignancies, with a high unmet need for more effective therapies. The topline results from DeLLphi-304 demonstrate overwhelming clinical benefit for people living with this devastating disease and affirm [tarlatamab] as SOC," Jay Bradner, MD, executive vice president of Research and Development at Amgen, stated in a news release. "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."

In May 2024, the FDA granted accelerated approval to tarlatamab for the treatment of patients with extensive-stage SCLC (ES-SCLC) with disease progression on or after platinum-based chemotherapy.2 That regulatory decision was based on data from phase 2 DeLLphi-301 trial (NCT05060016).

Findings from DeLLphi-301 supporting the accelerated approval showed that evaluable patients with relapsed/refractory ES-SCLC with disease progression following platinum-based chemotherapy (n = 99) achieved an overall response rate (ORR) of 40% (95% CI, 31%-51%). The median duration of response (DOR) was 9.7 months (range, 2.7 to 20.7+). The ORR was 52% (95% CI, 32% -71%) in patients with platinum-resistant SCLC (n = 27) and 31% (95% CI, 18%-47%) in patients with platinum-sensitive SCLC (n = 42).

DeLLphi-304 Background

The multicenter, randomized, open-label, phase 3 study enrolled patients at least 18 years of age with histologically or cytologically confirmed SCLC who experienced disease progression or recurrence following 1 platinum-based regimen.3 Other key inclusion criteria comprised measurable disease per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, a life expectancy of at least 12 weeks, and adequate organ function.

Patients were excluded if they had symptomatic central nervous system (CNS) metastases (with some exceptions); a diagnosis or suspicion of leptomeningeal disease; active autoimmune disease requiring systemic therapy within 2 years of enrollment; a history of solid organ transplantation; and myocardial infarction and/or symptomatic congestive heart failure within 12 months of first study treatment.

Prior treatment with tarlatamab or any chemotherapy agent utilized in the study was not permitted, and only 1 line of prior systemic therapy for SCLC was allowed.

Patients were randomly assigned 1:1 to receive tarlatamab or chemotherapy per local SOC with lurbinectedin (Zepzelca), topotecan, or amrubicin.

Along with the primary end point of OS, secondary end points included progression-free survival (PFS), ORR, disease control rate, DOR, landmark PFS and OS rates, safety, quality of life, and pharmacokinetics.

The prescribing information for tarlatamab includes warnings for cytokine release syndrome (CRS) and neurological toxicity, including immune effector cell–associated neurotoxicity syndrome (ICANS).1

Previously reported pooled safety data showed that CRS was reported in 55% of patients treated with tarlatamab at grade 1 (34%), grade 2 (19%), grade 3 (1.1%), and grade 4 (0.5%). Recurrent CRS occurred in 24% of patients at grade 1 (18%) and grade 2 (6%).

Neurological toxicity—including ICANS—was reported in 47% of patients, and 10% of patients experienced grade 3 or higher events. The most common neurological toxicities included headache (14%), peripheral neuropathy (7%), dizziness (7%), insomnia (6%), muscular weakness (3.7%), delirium (2.1%), syncope (1.6%), and neurotoxicity (1.1%).

References

1. Imdelltra demonstrated superior overall survival in small cell lung cancer. News release. Amgen. April 11, 2025. Accessed April 11, 2025. https://www.prnewswire.com/news-releases/imdelltra-demonstrated-superior-overall-survival-in-small-cell-lung-cancer-302426291.html
2. FDA grants accelerated approval to tarlatamab-dlle for extensive stage small cell lung cancer. FDA. May 16, 2024. Accessed April 11, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer
3. Study comparing tarlatamab with standard of care chemotherapy in relapsed small cell lung cancer (DeLLphi-304). ClinicalTrials.gov. Updated August 28, 2024. Accessed April 11, 2025. https://www.clinicaltrials.gov/study/NCT05740566