Adding tarlatamab-dlle to durvalumab maintenance extended survival in extensive-stage small cell lung cancer in the phase 3 DeLLphi-305 trial.
First-line maintenance therapy with tarlatamab-dlle (Imdelltra) plus durvalumab (Imfinzi) improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) vs durvalumab alone in patients with
In September 2026, Amgen announced that the trial had met its primary end point of OS at a planned interim analysis.2 The data were presented at the
The combination also improved progression-free survival (PFS), the key secondary end point. At a median follow-up of 13.9 months in both arms, the median PFS was 7.4 months (95% CI, 5.6-9.1) with tarlatamab plus durvalumab vs 1.9 months (95% CI, 1.9-2.0) with durvalumab alone (HR, 0.34; 95% CI, 0.28-0.42; P < .001). The 12-month PFS rates were 38% vs 10%, respectively.
“DeLLphi-305 outcomes support tarlatamab plus durvalumab as a new standard of care first-line maintenance therapy in ES-SCLC,” said Jacob Sands, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, in a presentation of the data during the Presidential Symposium.
DeLLphi-305 enrolled adults with ES-SCLC and an ECOG performance status of 0 or 1 whose disease had not progressed after 4 cycles of induction platinum/etoposide plus durvalumab; patients with asymptomatic untreated or treated brain metastases were eligible. Patients (n = 563) were randomly assigned 1:1 to tarlatamab at 10 mg every 2 weeks plus durvalumab at 1500 mg every 4 weeks, or durvalumab alone at 1500 mg every 4 weeks, until disease progression or unacceptable toxicity.
Randomization was stratified by brain and/or liver metastases (yes vs no), response to induction chemoimmunotherapy (complete or partial response vs stable disease), and prior platinum (cisplatin vs carboplatin). OS, PFS, and objective response were tested hierarchically, and the interim analysis was triggered at 243 deaths (61% information fraction).
The median age was 65.0 years in both arms; 19.5% vs 19.9% of patients had current or prior brain metastases, and 31.2% vs 33.8% had current or prior liver metastases. Patients were monitored on site for 1 to 2 hours after the first 2 tarlatamab doses, or for 6 to 8 hours in certain regions. In September 2026, the FDA shortened the labeled monitoring period after the first 2 doses of tarlatamab to 6 to 8 hours.4
The HR for death favored the combination in patients with current or prior brain metastases (n = 111; HR, 0.49; 95% CI, 0.26-0.93), patients with current or prior liver metastases (n = 183; HR, 0.41; 95% CI, 0.28-0.61), and patients with stable disease after induction therapy (n = 64; HR, 0.40; 95% CI, 0.19-0.85). In patients enrolled in the Americas (n = 75), the HR was 0.82 (95% CI, 0.39-1.71). PFS HRs ranged from 0.23 to 0.54 across prespecified subgroups with estimable HRs.
Among patients with measurable disease at randomization, the objective response rate per investigator-assessed RECIST 1.1 was 26.4% (95% CI, 20.9%-32.5%) with the combination (n = 235) vs 4.1% (95% CI, 2.0%-7.4%) with durvalumab alone (n = 244; P < .001). Confirmed complete responses occurred in 0.9% vs 0.4% of patients, respectively. The median duration of response (DOR) was 12.7 months (95% CI, 7.4-NE) vs 5.6 months (95% CI, 3.6-NE); the 6-month DOR rates in the respective arms were 70% vs 38%. At 12 months, the DOR rate in the tarlatamab/durvalumab arm was 52%.
Sands noted that response rate has limited interpretive value in the maintenance setting, where patients enter after already benefiting from induction therapy. He added that oligoprogression treated with radiation allowed some patients to remain on study therapy; at the data cutoff date of July 7, 2026, 43.6% vs 11.4% of patients remained on treatment.
OS follow-up is ongoing.
The median duration of treatment was 46.9 weeks (interquartile range [IQR], 16.4-65.6) with the combination (n = 282) vs 8.1 weeks (IQR, 4.1-20.1) with durvalumab alone (n = 278). Grade 3 or higher treatment-emergent adverse effects occurred in 46.8% vs 40.6% of patients. Treatment-related adverse effects (TRAEs) of any grade occurred in 95.0% vs 52.2%, and grade 3 or higher TRAEs were reported in 20.9% vs 10.8% of patients, respectively; those occurring in at least 1% of patients receiving the combination included neutrophil count decrease, neutropenia, and decreased appetite. TRAEs led to tarlatamab discontinuation in 3.2% of patients. No fatal TRAEs occurred with the combination vs 2 (0.7%) with durvalumab alone.
Cytokine release syndrome (CRS) occurred in 49.6% vs 1.4% of patients in the tarlatamab/durvalumab and durvalumab-alone arms, respectively. With the combination, grade 2 CRS occurred in 7.4% and grade 3 CRS in 1 patient (0.4%), with no grade 4 or fatal events. CRS interventions included corticosteroids (21.6%), tocilizumab (Actemra; 3.9%), and low-flow oxygen (1.4%). Immune effector cell–associated neurotoxicity syndrome occurred in 1.1% of patients receiving the combination, with no grade 3 or higher cases.
