8006 Background: Brain metastases (BM) are common in patients (pts) with SCLC and are associated with poor outcomes. Tarlatamab, a bispecific T-cell engager (BiTE) immunotherapy, demonstrated superior overall survival versus CTx in pts with SCLC following progression on or after platinum-based CTx in the DeLLphi-304 study, including pts with history of BM (prior or current) at baseline (OS HR 0.45 95% CI: 0.31–0.65). Here we compare the intracranial efficacy of tarlatamab vs CTx. Methods: Pts were randomized 1:1 to receive tarlatamab or CTx (topotecan, lurbinectedin or amrubicin) as 2L treatment for SCLC. Pts with stable asymptomatic brain metastases were eligible; prior CNS treatment was required until protocol amendment 3. Baseline brain imaging by contrast enhanced MRI was mandatory for all pts at screening and repeated at all subsequent imaging assessments for pts with a history of BM at baseline. A post hoc analysis on intracranial efficacy was performed by BICR per mRANO-BM. Given that most pts had prior CNS treatment, specified outcomes were CR, non-CR/non-PD, and PD. Results: BM at baseline were present in 98/254 pts (39%) in the tarlatamab arm and 99/255 (39%) in the CTx arm, of whom 75/98 (77%) and 69/99 (70%) had prior CNS treatment, respectively. A CNS full analysis set (FAS) was specified to include pts who had both a baseline scan and ≥ 1 postbaseline scan (tarlatamab-67; CTx-56 pts). In pts in FAS, treatment with tarlatamab resulted in longer CNS PFS than CTx (median: 6.5 mos vs 4.2 mos; HR, 0.40 95% CI: 0.24–0.66; Table). CNS tumor shrinkage of ≥30% was observed in 56% of pts with tarlatamab vs 38% with CTx. CNS complete response was observed in 15% of pts with tarlatamab vs 5% with CTx, with longer CNS duration of complete response (DOCR) (not estimable NE vs 3.6 mo) and longer CNS duration of disease control (DODC) (8.2 vs 5.2 mo) for pts in the tarlatamab arm. Pts with BM at baseline had longer OS with tarlatamab vs CTx (median OS: 13.9 vs 6.8 mos; HR, 0.51 95% CI: 0.34–0.74). In pts with BM at baseline, treatment-emergent adverse events (TEAEs) of any grade (gr)/gr 3/gr 4/gr 5 occurred in 99%/38%/9%/7% for tarlatamab vs 100%/38%/40%/10% for CTx. In pts treated with tarlatamab, the incidence of CRS and ICANS was 54% and 9% in pts with BM at baseline vs 58% and 4% in pts without BM at baseline, respectively. Conclusions: Tarlatamab demonstrated increased intracranial efficacy with longer CNS PFS and OS vs CTx in pts with stable, treated and untreated asymptomatic BM. These results affirm tarlatamab as the 2L standard of care for SCLC, even in pts with BM. Clinical trial information: NCT05740566 . Tarlatamabn = 67 CTxn = 56 CNS PFS, mos (95% CI) 6.5 (4.3, 13.7) 4.2 (2.9, 5.5) CNS Complete Response, n (%) 10 (15%) 3 (5%) CNS DOCR, mos (95% CI) NE (2.9, NE) 3.6 (3.1, NE) CNS DODC, mos (95% CI) 8.2 (6.3, NE) 5.2 (4.2, 6.2) CNS tumor shrinkage of ≥30%, % (n/N) a 56% (9/16) 38% (5/13) a Assessed in pts with ≥1 lesion that was ≥ 10 mm.
Mountzios et al. (2026) studied this question.