Tarlatamab versus chemotherapy (CTx) as second-line (2L) treatment for small cell lung cancer (SCLC): Primary analysis of Ph3 DeLLphi-304.

LBA8008 Background: Tarlatamab, a bispecific T-cell engager (BiTE) immunotherapy, demonstrated promising activity in patients (pts) with previously treated SCLC in phase 1/2 trials. We report results from the primary analysis of the randomized controlled, phase 3 DeLLphi-304 study, evaluating tarlatamab vs CTx in pts with SCLC following progression on or after platinum-based chemotherapy. Methods: Pts were randomized 1:1 to tarlatamab or CTx (topotecan, lurbinectedin or amrubicin), stratified by prior treatment with a PD-(L)1 inhibitor, chemotherapy-free interval, brain metastases, and intended CTx. Primary endpoint was overall survival (OS). Key secondary endpoints were progression-free survival (PFS) and patient-reported outcomes (PRO). Other secondary endpoints included objective response rate (ORR), duration of response (DOR), disease control rate (DCR), and safety. Results: 509 pts were randomized (254, tarlatamab; 255, CTx). At median follow-up of 11.2 months (mo) for tarlatamab and 11.7 mo for CTx, pts in the tarlatamab arm had significantly longer OS (median OS: 13.6 vs 8.3 mo; hazard ratio [HR], 0.60 [95% CI: 0.47, 0.77]; P < 0.001) and PFS (median PFS: 4.2 vs 3.2 mo; HR, 0.72 [95% CI: 0.59, 0.88]; P < 0.001) vs pts in the CTx arm. Tarlatamab improved cancer-related symptoms of dyspnea and cough compared to CTx (Table). Lower rates of grade (Gr) ≥3 treatment-related adverse events (TRAEs) occurred with tarlatamab vs CTx (27% vs 62%); discontinuations due to TRAEs were lower with tarlatamab (3% vs 6%). The most common Gr ≥3 TRAEs were neutropenia (4%) and lymphopenia (4%) with tarlatamab and anemia (28%) and neutropenia (22%) with CTx. Cytokine release syndrome with tarlatamab was primarily low grade (42% Gr1; 13% Gr2; 1% Gr3) and manageable. Conclusions: The DeLLphi-304 trial showed tarlatamab significantly improved OS, PFS, and PROs, with a favorable safety and tolerability profile compared to CTx in pts with SCLC that progressed on or after initial platinum-based CTx, defining a new standard of care for these patients. Clinical Trial Information: NCT05740566; Legal entity responsible: Amgen Inc.; Funding: Amgen Inc.; Editorial acknowledgement: Medical writing support for the development of this abstract was provided by Sukanya Raghuraman, PhD, of Cactus Life Sciences, part of Cactus Communications, and was funded by Amgen Inc. Clinical trial information: NCT05740566 . Tarlatamab (n=254) CTx*(n=255) Tarlatamab treatment effect ( P -value) Median OS, mo (95% CI) 13.6 (11.1-NE) 8.3 (7.0-10.2) HR = 0.60 ( P < 0.001) Median PFS, mo (95% CI) 4.2 (3.0-4.4) 3.2 (2.9-4.2) HR = 0.72 ( P < 0.001) ORR, % (95% CI) 35 (29-41) 20 (16-26) Odds ratio = 2.13 Median DOR, mo (95% CI) 6.9 (4.5-12.4) 5.5 (4.2-5.7) — DCR, % (95% CI) 68 (62-74) 64 (58-70) — Dyspnea score, change from baseline after18 wks † , mean (95% CI) -1.94 (-4.32, 0.45) 7.20 (4.58-9.81) MD = -9.14 ( P < 0.001) Cough score, pts with improvement 18 wks after baseline ‡ , n (%) 41 (16) 23 (9) OR = 2.04 ( P = 0.012) Chest pain score, pts with improvement 18 wks after baseline ‡ , n (%) 22 (9) 9 (4) OR = 1.84 ( P = 0.100 § ) MD: mean difference; NE: not estimable; wks, weeks. *Topotecan (n=185), lurbinectedin (n=47), or amrubicin (n=23).