Bispecific antibody combo extends survival in small cell lung cancer

Overview

Updated 2 hours ago

Small cell lung cancer in its extensive stage has held median survival near a year for decades. A phase 3 trial presented Oct. 24 at the ESMO Congress in Madrid nearly doubled that, to 21.1 months.

The winning combination pairs Amgen's IMDELLTRA (tarlatamab) with AstraZeneca's IMFINZI (durvalumab) as first-line maintenance after induction chemo-immunotherapy. Risk of death fell 58% versus durvalumab alone (hazard ratio 0.42). Nearly 80% of patients on the combo were alive at one year, versus 53% on durvalumab alone. Results ran simultaneously in the New England Journal of Medicine.

Why it matters

If approved, patients with the deadliest lung cancer subtype gain roughly eight months of life and a real shot at durable disease control.

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Key Indicators

58%

Reduction in risk of death

Tarlatamab plus durvalumab vs durvalumab alone (hazard ratio 0.42)

21.1 months

Median overall survival, combination arm

12.7 months with durvalumab alone; an 8.4-month gain

80%

One-year survival, combination arm

53% with durvalumab alone

7.4 months

Median progression-free survival, combination arm

1.9 months with durvalumab alone; a 66% risk reduction

Voices

Curated perspectives — historical figures and your fellow readers.

Ever wondered what historical figures would say about today's headlines?

People Involved

Jacob Sands

Associate Chief, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute

Presented DeLLphi-305 results at the ESMO Congress 2026 Presidential Symposium

Organizations Involved

Amgen Inc.

Biopharmaceutical company

Developer and marketer of IMDELLTRA (tarlatamab)

Thousand Oaks, California-based biopharma that developed tarlatamab, a bispecific T-cell engager targeting DLL3.

AstraZeneca

Biopharmaceutical company

Developer and marketer of IMFINZI (durvalumab)

British-Swedish pharma whose PD-L1 inhibitor durvalumab is already a first-line standard in extensive-stage small cell lung cancer.

Dana-Farber Cancer Institute

Cancer research and treatment center

Home institution of the presenting investigator for DeLLphi-305

Boston-based cancer center that helped conduct and present the DeLLphi-305 trial.

Timeline

September 2026 October 2026

4 events Latest: Today

Tap a bar to jump to that date

October 2026
Full results: 58% death risk reduction
Today Study result

ESMO Presidential Symposium and New England Journal of Medicine publish DeLLphi-305: median OS 21.1 versus 12.7 months.
Today
DeLLphi-303 update: 37.9-month median OS
Today Study result

Phase 1b maintenance data at 30.8-month follow-up; 58.1% of patients alive at two years.
Today
DeLLphi-304 confirms later-line benefit
Today Study result

Phase 3 in previously treated disease: 13.6 versus 8.4 months OS; 38% death risk reduction at 23-month follow-up.
Today
September 2026
DeLLphi-305 hits primary survival endpoint
Study result

Amgen announces tarlatamab plus durvalumab improved overall survival in first-line maintenance ES-SCLC; details withheld.
September 8th, 2026

Scenarios

FDA clears Imdelltra for first-line maintenance

Likely Resolves by End of 2027

Discussed by: Amgen press release; Dana-Farber

Amgen has said it will share the DeLLphi-305 data with global regulators. A supplemental biologics license application would expand tarlatamab from its approved later-line role to first-line maintenance, where the 58% death-risk reduction and 21.1-month median survival represent the largest gain seen in extensive-stage disease. Approval would make the drug available to newly diagnosed ES-SCLC patients who respond to induction therapy.

Guidelines name tarlatamab plus durvalumab the new standard

Likely Resolves by End of 2027

Discussed by: Dana-Farber; ESMO 2026 presenters

Jacob Sands told the ESMO Congress the combination "sets a new standard of care." If the NCCN or ESMO clinical practice guidelines adopt tarlatamab plus durvalumab as a preferred or category 1 first-line maintenance regimen, it would codify the practice change beyond regulatory approval and shape reimbursement decisions. This typically follows regulatory clearance but can move on its own.

A rival DLL3 bispecific narrows Amgen's lead

Possible Resolves by End of 2028

Discussed by: FiercePharma, citing an ESMO abstract

FiercePharma reported on an ESMO abstract where a DLL3-targeting bispecific added to Roche's atezolizumab (Tecentriq) also reduced death risk in first-line ES-SCLC. A competitor posting positive phase 3 data in the same setting would give doctors and payers a second option and shrink Amgen's pricing power, moving the field from a single-drug standard to a competitive market.

Historical Context

3 moments from history that rhyme with this story — and how they unfolded.

September 2018

IMpower133 trial (2018)

Roche's atezolizumab (Tecentriq) plus carboplatin and etoposide showed a median overall survival of 12.3 months versus 10.3 months for chemotherapy alone in first-line extensive-stage small cell lung cancer. It was the first trial to show a checkpoint inhibitor improved survival in ES-SCLC.

Then

Chemo-immunotherapy became the new first-line standard, replacing decades of chemotherapy-only treatment.

Now

Checkpoint inhibitors became the backbone of ES-SCLC treatment, though median survival gains stayed modest, around two months.

Why this matters now

DeLLphi-305 builds directly on that backbone, adding a T-cell engager atop durvalumab and nearly doubling median survival — a far larger gain than the original checkpoint inhibitor shift.

June 2019

CASPIAN trial (2019)

AstraZeneca's durvalumab plus platinum-etoposide showed a median overall survival of 13.0 months versus 10.3 months for chemotherapy alone, establishing durvalumab-plus-chemo as a first-line standard in ES-SCLC.

Then

Durvalumab gained approval in first-line ES-SCLC and became the control arm for subsequent trials.

Now

The regimen's median survival of roughly a year became the benchmark DeLLphi-305 was designed to beat.

Why this matters now

DeLLphi-305 used durvalumab alone as the comparator; adding tarlatamab extended that ~13-month benchmark to 21.1 months.

December 2014

Blincyto approval (2014)

The U.S. Food and Drug Administration approved blinatumomab (Blincyto), the first bispecific T-cell engager, for a rare form of acute lymphoblastic leukemia. The drug works by binding CD19 on cancer cells and CD3 on T cells, forcing the immune system to attack the tumor.

Then

Blincyto established the bispecific T-cell engager as a viable drug class in blood cancers.

Now

The mechanism took a decade to show benefit in solid tumors; tarlatamab is the first bispecific T-cell engager to demonstrate an overall survival gain in a first-line maintenance setting for a solid cancer.

Why this matters now

Tarlatamab uses the same CD3-bridging mechanism as Blincyto but targets DLL3 on small cell lung cancer cells — and now with a 58% death-risk reduction in the first-line setting.