Lungenkarzinom
DeLLphi-304 (ES-SCLC): Tarlatamab verbessert die intrakranielle Kontrolle
Beschreibung
Tarlatamab represents a new standard of care after platinum failure in end-stage small cell lung cancer (ES-SCLC). This substance is a bispecific T-cell engager that binds DLL3 (delta-like ligand 3) on tumor cells and CD3 on T cells. Tarlatamab was approved by the European Commission on June 1, 2026, as monotherapy for adult patients with ES-SCLC who require subsequent systemic therapy after progression on or following platinum-based first-line treatment. Tarlatamab is expected to be available in Germany by the end of July 2026. Furthermore, tarlatamab and other T-cell engagers, such as obrixtamig, are being evaluated in the first-line setting in combination with platinum-based chemotherapy in global phase III trials.
The central basis for the evaluation of tarlatamab after platinum failure is the randomized, open-label phase III trial DeLLphi-304 ( NCT05740566 ) [2] . This trial enrolled 509 patients with ES-SCLC after progression on platinum-based first-line therapy with or without programmed cell death (ligand) 1 (PD-[L]1) inhibition and randomized 1:1 to tarlatamab (n = 254) versus chemotherapy at the physician's choice (n = 255; topotecan, lurbinectedin, or amrubicin). The primary endpoint was overall survival (OS). In the primary analysis, tarlatamab demonstrated a significant survival benefit over standard therapy, with a median OS of 13.6 versus 8.3 months (hazard ratio: 0.60). Progression-free survival (PFS) was also improved. The published median values were 4.2 months versus 3.7 months.
At this year's ASCO meeting, a post-hoc analysis of the DeLLphi-304 trial of patients with brain metastases at baseline was presented [3] . These patients were asymptomatic and could be previously treated or untreated. After 6 months, 53.9% of patients treated with tarlatamab had no CNS progression (CNS = central nervous system), compared to 27.0% with chemotherapy (Fig. 2). The median CNS progression-free survival (PFS) was 6.5 versus 4.2 months. Furthermore, in the subgroup with initial brain metastases, the 12-month overall survival (OS) rate was 51.1% with tarlatamab compared to 26.0% with standard chemotherapy. In the overall cohort, the risk of CNS progression was reduced by 46%. Overall, these data suggest clinically relevant intracranial activity of tarlatamab.
Fig. 2: CNS-PFS with tarlatamab compared to standard in ES-SCLC patients with brain metastases in the DeLLphi-304 study (modified from [3] )
"In summary, the risk of CNS progression in the entire cohort, i.e., in patients with and without brain metastases at study enrollment, was reduced by 46% by tarlatamab." Dr. Michael Pogorzelski