Tarlatamab Improves Overall Survival in Extensive-Stage SCLC

Tarlatamab-dlle (Imdelltra; Amgen) significantly improved overall survival (OS) among patients with small cell lung cancer (SCLC) compared with local standard-of-care chemotherapy in the phase 3 DeLLphi-304 trial (NCT05740566), according to a press release from Amgen.1 OS was the primary end point in the trial, and data from the planned interim analysis will be presented at an upcoming scientific meeting.

Last year, the FDA granted accelerated approval to tarlatamab for patients with extensive-stage SCLC who experience progression while on or after receiving platinum-based chemotherapy.2 The approval was based on a phase 2 trial that showed a 40% objective response rate (97.5% CI, 29-52) among previously treated patients with SCLC.3

OS was the primary end point in the trial, and data from the planned interim analysis will be presented at an upcoming scientific meeting. | Image credit: Crystal light - stock.adobe.com

The DeLLphi-304 trial recruited patients who had experienced progression on or after a single line of platinum-based therapy.1 Patients in several countries were randomized to receive either tarlatamab or chemotherapy with lurbinectedin or topotecan. At the interim analysis, patients in the tarlatamab treatment group experienced a statistically significant and clinically meaningful improvement in OS compared with chemotherapy.

“Small cell lung cancer is one of the most aggressive malignancies, with a high unmet need for more effective therapies,” said Jay Bradner, MD, the company’s vice president of research and development, in a press release. “The topline results from DeLLphi-304 demonstrate overwhelming clinical benefit for people living with this devastating disease and affirm Imdelltra as standard of care.”

Tarlatamab is a bispecific T-cell engager that binds to delta-like ligand 3 (DLL3) on tumor cells and CD3 on T cells, activating T cells to attack DLL3-expressing cancer cells. The DLL3 protein is expressed on the surface of SCLC cells in approximately 85-96% of patients with SCLC but is “minimally expressed” on healthy cells.

In the interim analysis, the safety profile for tarlatamab was consistent with previous trials. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have both been reported in patients receiving the therapy. CRS occurred in 55% of patients who received the therapy, though only 1.1% of patients had grade 3 CRS and 0.5% of patients had grade 4 CRS, the press release noted. In the phase 2 DeLLphi-301 trial, grade 3 CRS was less common in patients receiving a 10 mg dose compared with those receiving a 100 mg dose. Overall, 47% of patients who received tarlatamab experienced neurologic toxicities, including ICANS; 10% experienced grade 3 events.

SCLC accounts for about 15% of the 2.4 million newly diagnosed cases of lung cancer each year, and the 5-year survival rate is just 5-10% across all stages combined, the press release noted. The new OS data affirm tarlatamab as the standard of care for eligible patients, according to Bradner.

“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,” he said in the press release.

Several tarlatamab trials are currently underway, including a phase 1b trial evaluating tarlatamab in combination with standard-of-care therapies in first-line extensive-stage SCLC, a phase 3 trial comparing tarlatamab in combination with durvalumab (Imfinzi; AstraZeneca) to durvalumab alone as first-line maintenance therapy in extensive-stage SCLC, and a phase 3 placebo-controlled trial examining tarlatamab following concurrent chemoradiotherapy in limited-stage SCLC, among others.

References

1. Amgen. Imdelltra demonstrated superior overall survival in small cell lung cancer. Published April 11, 2025. Accessed April 12, 2025.https://www.amgen.com/newsroom/press-releases/2025/04/imdelltra-demonstrated-superior-overall-survival-in-small-cell-lung-cancer
2. U.S. Food and Drug Administration. FDA grants accelerated approval to tarlatamab-dlle for extensive stage small cell lung cancer. FDA News Release. Published May 16, 2024. Accessed April 12, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer
3. Ahn MJ, Cho BC, Felip E, et al. Tarlatamab for patients with previously treated small-cell lung cancer. N Engl J Med. 2023;389(22):2063-2075. doi:10.1056/NEJMoa2307980