Extended DeLLphi-304 Follow-Up Confirms Durable Survival Benefit With Tarlatamab in Previously Treated SCLC

Tarlatamab-dlle (Imdelltra) sustained an overall survival (OS) improvement vs chemotherapy in patients with small cell lung cancer (SCLC) whose disease progressed during or after first-line platinum-based therapy, with no new safety signals emerging, according to extended follow-up data from the phase 3 DeLLphi-304 trial (NCT05740566) presented at the 2026 ESMO Congress.¹

Benefits with tarlatamab extended across progression-free survival (PFS), response durability, and sustained disease control, and the separation of the Kaplan-Meier curves persisted over time.

Findings, which were published simultaneously in Annals of Oncology, showed that at a median follow-up of 23.3 months in the tarlatamab arm (n = 254) and 22.8 months in the chemotherapy arm (n = 255), the median OS was 13.6 months vs 8.4 months, respectively (HR, 0.62; 95% CI, 0.51-0.76). The 18-month OS rates were 42% with tarlatamab vs 24% with chemotherapy, and the 24-month OS rates were 30% vs 15%, respectively. The data cutoff was February 18, 2026.

"Extended follow-up of what we've seen here, and also in the [phase 3 ]DeLLphi-305 trial [NCT06211036], really reinforces tarlatamab as the standard-of-care choice after first-line platinum-based chemotherapy for patients with extensive-stage SCLC [ES-SCLC]," lead study author Charles M. Rudin, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, New York, said during the presentation of the data. "The DeLLphi-304 trial continues to demonstrate durable clinical benefit with tarlatamab vs chemotherapy, [with] a safety profile that I think continues to reassure us that this is safe and preferable, frankly, to chemotherapy."

What OS data were previously reported from DeLLphi-304?

In the previously reported primary analysis, which was conducted at the first planned interim analysis with a median follow-up of 11.2 months for tarlatamab and 11.7 months for chemotherapy, the median OS was 13.6 months vs 8.3 months (HR, 0.60; P < .001).²

Prior data from DeLLphi-304 supported the November 2025 traditional FDA approval of tarlatamab for the treatment of adult patients with ES-SCLC with disease progression on or following platinum-based chemotherapy.³

Notably, in the DeLLphi-305 trial, findings from which were also presented at ESMO 2026, tarlatamab plus durvalumab (Imfinzi) given as first-line maintenance therapy improved OS, PFS, and overall response rate (ORR) vs durvalumab alone in patients with ES-SCLC whose disease had not progressed after first-line chemoimmunotherapy with durvalumab.⁴

How was DeLLphi-304 designed?

The randomized, controlled, phase 3 DeLLphi-304 trial enrolled 509 patients at least 18 years of age with SCLC that progressed during or after first-line platinum-based therapy and an ECOG performance status of 0 or 1.¹ Patients with treated or untreated asymptomatic brain metastases were eligible.

Patients were randomly assigned 1:1 to receive tarlatamab or the investigator's choice of chemotherapy, which consisted of topotecan (n = 185), lurbinectedin (n = 47), or amrubicin (n = 23; Japan only), each given in 21-day cycles.

Randomization was stratified by prior anti–PD-1/PD-L1 therapy, chemotherapy-free interval (< 90 days vs ≥ 90 days to < 180 days vs ≥ 180 days), presence of brain metastases, and planned chemotherapy (topotecan/amrubicin vs lurbinectedin).

OS served as the primary end point. Secondary end points included PFS, objective response rate (ORR), disease control, duration of response (DOR), patient-reported outcomes, and safety.

What did the additional efficacy analyses show?

At a median follow-up of 22.2 months for tarlatamab and 21.9 months for chemotherapy, the median PFS was 4.2 months vs 3.2 months, respectively (HR, 0.69; 95% CI, 0.57-0.84). The respective 12-month PFS rates were 21% vs 6%, and the 18-month PFS rates were 16% vs 4%.

"The message is not in the median. The message is in the tail [of the survival curves]. That's what people care about," Rudin said, noting that the tarlatamab PFS curve reached a plateau.

The ORR was 35% (95% CI, 30%-42%) with tarlatamab vs 20% (95% CI, 16%-26%) with chemotherapy. Among confirmed responders (tarlatamab, n = 90; chemotherapy, n = 52), the median DOR was 7.1 months (95% CI, 4.5-12.4) vs 5.5 months (95% CI, 4.2-5.7), respectively. The respective Kaplan-Meier–estimated DOR rates were 56% (95% CI, 45%-66%) vs 30% (95% CI, 18%-43%) at 6 months and 42% (95% CI, 31%-52%) vs 10% (95% CI, 4%-20%) at 12 months.

Sustained disease control lasting at least 52 weeks was achieved by 24% of patients in the tarlatamab arm vs 4% of those in the chemotherapy arm.

What did the safety analysis show?

In the safety population (tarlatamab, n = 252; chemotherapy, n = 244), the median duration of treatment was 18.2 weeks (range, 0.1-128.9) with tarlatamab vs 10.9 weeks (range, 0.1-118.1) with chemotherapy. Any-grade treatment-related adverse effects (TRAEs) occurred in 93.3% vs 91.4% of patients, respectively, and the respective rates of grade 3 or higher TRAEs were 27.8% vs 62.7%.

Serious TRAEs were reported in 28.6% of patients in the tarlatamab arm vs 31.1% of patients in the chemotherapy group. TRAEs led to dose interruption and/or reduction in 19.4% vs 55.3% of patients, respectively, and to treatment discontinuation in 3.2% vs 6.6%, respectively.. Fatal TRAEs occurred in 1 patient (0.4%) in the tarlatamab arm, which was attributed to immune effector cell–associated neurotoxicity syndrome (ICANS), and 4 patients (1.6%) in the chemotherapy arm.

Cytokine release syndrome (CRS) and ICANS occurred predominantly during the first 2 doses of tarlatamab and were primarily grade 1 or 2. At cycle 1 day 1, grade 1, grade 2, and grade 3 or higher CRS occurred in 27.8%, 10.7%, and 0.8% of patients, respectively; at cycle 1 day 8, these rates were 30.2%, 4.4%, and 0.4%. The cumulative incidence of CRS from cycle 3 onward was 1.2%, and no grade 4/5 CRS was reported. No ICANS events occurred after cycle 1 day 8.

When TRAEs were assessed by time on treatment, the most common TRAE with tarlatamab in the first 3 months was CRS (56.3%), which occurred in 0% of patients treated for 3 to 12 months and in 1.6% of those treated for at least 12 months. In contrast, hematologic toxicities with chemotherapy persisted with longer exposure; among the 10 patients who remained on chemotherapy for at least 12 months, rates of anemia and neutropenia were each 60.0%.

"There's no increase in toxicity with longer-term treatment on tarlatamab. In fact, probably the opposite," Rudin said. "The toxicities occur early and then tend to get better over time."

References

1. Rudin CM, Ahn MJ, Schuler M, et al. Tarlatamab in previously treated SCLC: extended follow-up of overall survival from the phase 3 DeLLphi-304 trial. Presented at: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract 3808O.
2. Mountzios G, Sun L, Cho BC, et al. Tarlatamab in small-cell lung cancer after platinum-based chemotherapy. N Engl J Med. 2025;393(4):349-361. doi:10.1056/NEJMoa2502099
3. FDA grants traditional approval to tarlatamab-dlle for extensive stage small cell lung cancer. FDA. November 19, 2025. Accessed October 26, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer
4. Sands J, Yoshida T, Ahn MJ, et al. Tarlatamab plus durvalumab vs durvalumab as first-line maintenance therapy following first-line durvalumab, platinum, and etoposide in extensive-stage small cell lung cancer: primary analysis of the phase 3 DeLLphi-305 trial. Presented at: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract LBA3.