Intracranial efficacy of tarlatamab versus chemotherapy as second-line treatment for small cell lung cancer: DeLLphi-304 phase 3 post hoc analysis

Background:

Brain metastases (BM) are common in patients with small cell lung cancer (SCLC) and are associated with poor outcomes. Tarlatamab, a bispecific T-cell engager (BiTE®) immunotherapy, demonstrated superior overall survival (OS) versus chemotherapy (CTx) in patients with SCLC following progression on or after platinum-based chemotherapy in the DeLLphi-304 study, including patients with a history of BM (prior or current) at baseline (OS hazard ratio [HR], 0.45 [95% confidence interval (CI): 0.31–0.65]). Here, we compare the intracranial efficacy of tarlatamab versus CTx.

Objectives:

Evaluate the intracranial efficacy of tarlatamab compared with chemotherapy in patients with SCLC and baseline BM.

Purpose:

To determine whether tarlatamab improves intracranial efficacy outcomes compared with CTx in previously treated patients with SCLC and BM.

Methods:

Patients were randomized 1:1 to receive tarlatamab or CTx (topotecan, lurbinectedin, or amrubicin) as second-line (2L) treatment for SCLC. Patients with stable, asymptomatic BM were eligible; prior central nervous system (CNS) treatment was required until protocol amendment 3. Baseline brain imaging by contrast-enhanced magnetic resonance imaging (MRI) was mandatory for all patients at screening and repeated at all subsequent imaging assessments for patients with a history of BM at baseline. A post hoc analysis of intracranial efficacy was performed by blinded independent central review (BICR) per modified Response Assessment in Neuro-Oncology Brain Metastases (mRANO-BM) criteria. Given that most patients had received prior CNS treatment, specified outcomes were complete response (CR), non-CR/non-progressive disease (PD), and PD.

Results:

BM at baseline were present in 98 of 254 patients (39%) in the tarlatamab arm and 99 of 255 (39%) in the CTx arm, of whom 75 of 98 (77%) and 69 of 99 (70%) had received prior CNS treatment, respectively. A CNS full analysis set (FAS) was specified to include patients who had both a baseline scan and ≥1 postbaseline scan (tarlatamab, n=67; CTx, n=56). Among patients in the FAS, treatment with tarlatamab resulted in longer CNS progression-free survival (PFS) than CTx (median, 6.5 months versus 4.2 months; HR, 0.40 [95% CI: 0.24–0.66]). CNS tumor shrinkage of ≥30% was observed in 56% of patients with tarlatamab versus 38% with CTx. CNS CR was observed in 15% of patients with tarlatamab versus 5% with CTx, with longer CNS duration of complete response (DOCR) (not estimable [NE] versus 3.6 months) and longer CNS duration of disease control (DODC) (8.2 versus 5.2 months) for patients in the tarlatamab arm. Patients with BM at baseline had longer OS with tarlatamab versus CTx (median OS, 13.9 versus 6.8 months; HR, 0.51 [95% CI: 0.34–0.74]). In patients with BM at baseline, treatment-emergent adverse events (TEAEs) of any grade/grade 3/grade 4/grade 5 occurred in 99%/38%/9%/7% with tarlatamab versus 100%/38%/40%/10% with CTx. In patients treated with tarlatamab, the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) was 54% and 9% in patients with BM at baseline versus 58% and 4% in patients without BM at baseline, respectively.

Conclusion:

Tarlatamab demonstrated increased intracranial efficacy with longer CNS PFS and OS versus CTx in patients with stable, treated or untreated asymptomatic BM. These results affirm tarlatamab as the 2L standard of care for SCLC, even in patients with BM.

Funding: Amgen Inc.

Prior Presentations:

Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2026, May 29–June 2, 2026, in Chicago, IL, USA.

© 2026 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2026 ASCO Annual Meeting. All rights reserved.