OnCo
trialsTrialPositive

DeLLphi-304

DeLLphi-304 was the first trial in which a T-cell engager improved survival in a common solid tumour.

OS 13.6 vs 8.3 months (HR 0.60). Presented ASCO 2025 plenary; NEJM.

Setting
Second-line small-cell lung cancer: tarlatamab vs chemotherapy
Phase
Phase 3
Sponsor
Amgen
Registry
NCT05740566
Headline result
OS HR 0.60.
Reported
2025
Enrolled
509
Replication
Confirms the single-arm DeLLphi-301 result (ORR 40%) that supported accelerated approval; first-line data (DeLLphi-305) pending.

Outcomes

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In plain words
What these results mean for people, not percentages
509 people took part
Overall survivalprimarysurvival endpoint
  • Median 13.6 vs 8.3 months with Tarlatamab compared with Chemotherapy (topotecan, lurbinectedin, or amrubicin); about 5.3 months longer for half the group.
  • A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
  • Put another way, the treated group had about 40 percent lower chance of the event at any given time (hazard ratio 0.6, likely range 0.47 to 0.77).
  • Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
Progression-free survivalsurrogate endpoint
  • Median 4.2 vs 3.7 months with Tarlatamab compared with Chemotherapy; about 0.5 months longer for half the group.
  • A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
  • Put another way, the treated group had about 29 percent lower chance of the event at any given time (hazard ratio 0.71, likely range 0.59 to 0.86).
  • This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
Objective response rateresponse endpoint
  • 35 vs 20 out of 100 had their tumour shrink with Tarlatamab compared with Chemotherapy; 15 more per 100.
  • Roughly one extra person helped for every 7 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
  • A response rate counts how many people had their tumours shrink by a set amount; shrinking is encouraging but does not by itself show that people live longer or feel better.
Be careful
  • These results apply to the people the trial enrolled: Second-line small-cell lung cancer: tarlatamab vs chemotherapy. People in a different situation may not see the same effect.

Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.

509 participants enrolled.

Overall survivalprimary
HR 0.6 (0.47–0.77) · p <0.001
Tarlatamab
13.6 mo
Chemotherapy (topotecan, lurbinectedin, or amrubicin)
8.3 mo
Source
Progression-free survival
HR 0.71 (0.59–0.86)
Tarlatamab
4.2 mo
Chemotherapy
3.7 mo
Source
Objective response rate
Tarlatamab35 of 100
Chemotherapy20 of 100
EndpointArmnValueHR (95% CI)pSource
Overall survivalprimaryTarlatamab25413.6 months0.6 (0.47–0.77)<0.001link
Chemotherapy (topotecan, lurbinectedin, or amrubicin)2558.3 months
Progression-free survivalTarlatamab—4.2 months0.71 (0.59–0.86)—link
Chemotherapy—3.7 months
Objective response rateTarlatamab—35%———
Chemotherapy—20%
Replication
Confirms the single-arm DeLLphi-301 result (ORR 40%) that supported accelerated approval; first-line data (DeLLphi-305) pending.

Key papers

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rctNew England Journal of Medicine 2023changed practice
DeLLphi-301: tarlatamab, a DLL3-targeting T-cell engager, in previously treated small-cell lung cancer

Patients with small-cell lung cancer that has relapsed after chemotherapy now have a drug that works far better than topotecan or lurbinectedin, and it is the first T-cell engager approved for a solid tumour. Treatment requires inpatient monitoring for the first doses because of cytokine release syndrome, which most centres now manage on a short-stay basis. It does not yet apply to first-line treatment, where trials are ongoing.

Connected

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Pages like this

not linked directly; found by shared links

cancers

1
Small-cell lung cancer

targets

1
DLL3

drugs

2
ApprovedBispecific T-cell engager (DLL3×CD3)
Tarlatamab · Imdelltra
ApprovedCytotoxic (topoisomerase-I inhibitor)
Topotecan · Hycamtin

key papers

1
DeLLphi-301: tarlatamab, a DLL3-targeting T-cell engager, in previously treated small-cell lung cancer