The phase 3 DeLLphi-304 study evaluated tarlatamab, a bispecific T-cell engager immunotherapy, versus chemotherapy in patients with small cell lung cancer (SCLC) that progressed on or after platinum-based chemotherapy. A total of 509 patients were randomized 1:1 to receive tarlatamab (n=254) or standard chemotherapy (n=255) consisting of topotecan, lurbinectedin, or amrubicin.1
Patients were stratified on multiple factors, including prior programmed death-ligand 1 inhibitor use, chemotherapy-free interval, brain metastases, and intended chemotherapy. The primary endpoint was overall survival (OS), with progression-free survival (PFS) and patient-reported outcomes via the EORTC-QLQ-C30 and EORTC-QLQ-LC13 as key secondary endpoints. Other secondary endpoints included objective response rate (ORR), disease control rate, duration of response (DOR), and safety.
At a median follow-up of 11.2 months for tarlatamab and 11.7 months for chemotherapy, tarlatamab demonstrated a significant improvement in OS (median OS, 13.6 vs 8.3 months; hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.47-0.77; P<.001) and PFS (median, 4.2 vs 3.7 months; HR, 0.71; 95% CI, 0.59-0.86; P=.002) compared with chemotherapy. Tarlatamab also improved EORTC-QLQ-C30 scores in dyspnea after 18 weeks compared with chemotherapy (change from baseline, 1.94 vs –7.20; least-squares mean difference, –9.14; 95% CI, –12.64 - –5.64). A greater number of patients also demonstrated improvement in cough (16% vs 9%) and chest pain scores (9% vs 4%) on the EORTC-QLQ-LC13. ORR (35% vs 20%) and DOR (6.9 months vs 5.5 months) also favored tarlatamab compared with chemotherapy. Safety analysis revealed lower rates of grade ≥3 treatment-related adverse events (TRAEs) with tarlatamab compared with chemotherapy (27% vs 62%), with fewer discontinuations caused by TRAEs (3% vs 6%). Common grade ≥3 TRAEs with tarlatamab included neutropenia (4%) and lymphopenia (4%), while anemia (28%) and neutropenia (22%) were more frequent with chemotherapy. Cytokine release syndrome with tarlatamab was primarily low grade (grade 1, 42%) and manageable.
The results establish tarlatamab as a promising new treatment option. Tarlatamab offers significant survival and progression benefits and improved tolerability compared with standard chemotherapy, and has the potential to set a new standard of care in the second line for this patient population.
Source
- Rudin CM, Mountzios GS, Sun L, et al. Tarlatamab versus chemotherapy (CTx) as second-line (2L) treatment for small cell lung cancer (SCLC): primary analysis of Ph3 DeLLphi-304. Presented at: 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract LBA8008.