ESMO Congress 2026

Tarlatamab is a bispecific T-cell engager (BiTE) targeting DLL3×CD3 that received US FDA approval for small cell lung cancer (SCLC) in 2024, one of the antibody new molecular entities approved that year, based on phase II data showing improved response rates and progression-free survival over standard of care in previously treated SCLC, with multiple phase III studies following ^[1][2][6]. SCLC is initially sensitive to platinum chemotherapy but develops resistance rapidly and carries a dismal prognosis, and the benefits of PD-(L)1 inhibitors and ADCs remain limited ^[4]. CRS is the main safety concern; the DeLLphi-300 substudy showed that with 6–8-hour outpatient monitoring in cycle 1, any-grade CRS was around 60%, comparable to 48-hour inpatient monitoring (62%), supporting feasibility for broader use ^[5].

The Presidential Symposium LBA3 at ESMO 2026 reported the phase III DeLLphi-305: after induction with first-line chemotherapy plus durvalumab in ES-SCLC, patients were randomized to tarlatamab plus durvalumab versus durvalumab alone as maintenance. Amgen announced on 8 September that the trial met its OS endpoint at an interim analysis; the figures presented were OS 21.1 vs 12.7 months (HR 0.42), PFS 7.4 vs 1.9 months (HR 0.34), CRS incidence 49.6% with grade ≥3 of only 0.4%. The presenter was Jacob Sands, 24 October (Saturday), 17:18, Hall 6.

Relative to prior knowledge, DeLLphi-305 advances tarlatamab's evidence from the previously treated setting ^[2][5] into first-line maintenance, directly combined with a PD-L1 inhibitor, and the OS HR 0.42 magnitude made it one of the three Presidential Symposium presentations. The live posts also discussed a second thread: an indirect contrast with IMforte (atezolizumab plus lurbinectedin maintenance, OS HR 0.73). The poster explicitly noted that cross-trial comparisons are inappropriate, though tarlatamab's OS benefit appeared numerically much greater; another post claimed tarlatamab enters the brain while the IMforte regimen does not — this reflects the poster's view, with no supporting data presented at the meeting, and remains to be confirmed.

As for limitations, only conference topline figures are available so far; OS maturity, subsequent lines of therapy, CNS efficacy, quality of life and the full safety profile await full publication. The durvalumab monotherapy arm's PFS was only 1.9 months, and whether the combination's benefit is durable requires longer follow-up.