A large trial has found that adding Amgen’s drug Imdelltra (tarlatamab) to AstraZeneca’s immunotherapy Imfinzi (durvalumab) helped people with advanced small cell lung cancer live longer than Imfinzi alone. The combination lowered the risk of death by 58% compared with Imfinzi by itself1. The full results were presented on Saturday, October 24, at the European Society for Medical Oncology (ESMO) congress in Madrid and published the same day in The New England Journal of Medicine2.
People who got both drugs lived a median of 21.1 months, against 12.7 months for those on Imfinzi alone1. Amgen had already said earlier that the study was successful; this is the first full look at the numbers1.
What the trial tested
Small cell lung cancer is the less common form of lung cancer, making up up to 15% of cases1. It is very aggressive. Only around 9% of people diagnosed are alive five years later, according to the American Cancer Society1. About two-thirds of patients are diagnosed at the “extensive” stage, when the cancer has spread beyond one side of the chest, and only 3.6% of those patients are alive five years after diagnosis, according to AstraZeneca figures cited by Credence Research3.
Standard first treatment combines chemotherapy with an immunotherapy such as Imfinzi, followed by Imfinzi on its own as “maintenance” to try to keep the cancer in check3. The trial, called DeLLphi-305, looked at that maintenance stage. It enrolled 563 people whose cancer had not grown after their first round of Imfinzi plus chemotherapy. They were randomly split into two equal groups: one got Imdelltra plus Imfinzi, the other got Imfinzi alone, until the cancer grew or side effects became too much2. The main question was how long people lived2.
The two drugs work in different ways. Imfinzi is an older type of immunotherapy that blocks a trick tumors use to hide from the immune system1. Imdelltra is a bispecific antibody, a drug with two “arms”: one grabs a protein called DLL3 on the cancer cells and the other grabs immune T cells, pulling the two together so the T cells can attack3. DLL3 is found on the cancer cells of roughly 85% to 96% of patients and rarely on healthy cells3.
The results so far
These are interim results, meaning a planned early look at the data, taken at a median follow-up of about 16 months4. Amgen reported:
- Survival: median overall survival of 21.1 months with both drugs versus 12.7 months with Imfinzi alone, a gain of more than eight months4.
- Alive at one year: nearly 80% in the combination group versus 53% on Imfinzi alone4.
- Time before the cancer grew: a median of 7.4 months versus 1.9 months, a 66% lower risk of the cancer growing or death4.
- Tumors shrinking: 26.4% of people on both drugs saw their tumors shrink by a set amount, compared with 4.1% on Imfinzi alone4.
The benefit was seen across pre-planned subgroups, including people whose cancer had spread to the brain or liver, groups that usually do worse2. Jacob Sands of Dana-Farber Cancer Institute, who presented the data, said:
“This trial is positive in every way. We have seen substantial improvement in median progression-free survival, substantial improvement in median overall survival, and we’re improving the time of disease control substantially for a broader group of patients than what we’ve seen from any prior study and any prior treatment.”2
Side effects and hospital monitoring
Adding a second drug brought more side effects. Serious treatment-related side effects occurred in 20.9% of people on both drugs and 10.8% on Imfinzi alone4. The most common serious ones with the combination included a drop in a type of white blood cell (3.2%), loss of appetite (2.1%), weakness (1.8%) and weight loss (1.8%)4.
About half of Imdelltra patients (49.6%) had cytokine release syndrome, an aggressive inflammatory reaction. Almost all cases were mild or moderate, with one severe case and no deaths from it1. A nerve-related side effect known as ICANS occurred in 1.1% of Imdelltra patients, none of them severe4. Side effects led to stopping treatment in 5.7% of people on the combination and 5.8% on Imfinzi alone1.
Because of these risks, patients were watched in a healthcare setting for 1 to 2 hours after their first two Imdelltra doses, or 6 to 8 hours in some regions including Europe4. The US label for Imdelltra carries boxed warnings, the strongest kind, for cytokine release syndrome and nerve problems3.
What it does not show yet
The results are early. Median follow-up was about 16 months, and Amgen said patients are still being followed1. How many people are alive after several years is not yet known.
The trial was “open-label,” meaning patients and doctors knew which treatment each person received2. That matters less for a hard measure like survival, but it can affect measures such as when doctors judge a tumor to have grown.
The comparison group received Imfinzi alone, so the trial shows what adding Imdelltra did on top of current care. It does not compare the combination with other new options. Credence Research notes that a rival combination from Jazz Pharmaceuticals and Roche, approved by the FDA in October 2025 for the same maintenance stage, was tested in a different trial with different patients, so direct comparisons are limited3.
The combination is not yet approved for this use3.
Who is behind it
The trial was sponsored by Amgen, which makes Imdelltra. AstraZeneca, which makes Imfinzi, supplied its drug and paid part of the costs2. Both companies stand to gain if the combination becomes standard care. Wall Street analysts estimate Imdelltra’s yearly sales could pass $2.5 billion by 2030, according to LSEG data reported by Reuters1.
Amgen’s chief medical officer, Paul Burton, called the results “unprecedented in advancing the treatment of extensive-stage small cell lung cancer” and said, “If you give Imdelltra earlier and earlier, you get bigger clinical benefit”1. Those are the company’s views; the trial tested one specific point in treatment.
How it fits the field
Imdelltra is already on the market. The FDA first cleared it in May 2024 for patients whose cancer grew on or after platinum-based chemotherapy3. That was an accelerated approval, based on how many tumors shrank and for how long5. A later trial of 509 patients, DeLLphi-304, found Imdelltra lowered the risk of death by 40% compared with standard chemotherapy in that later setting, with median survival of 13.6 months versus 8.3 months5.
The new trial moves the drug earlier, to people who have just finished first treatment. Amgen also presented updated numbers from a smaller early-stage study, DeLLphi-303, where median survival was 37.9 months from the start of maintenance with Imdelltra plus an immunotherapy, and 58.1% of patients were alive at two years4. That study had no comparison group, so it cannot show on its own how much Imdelltra added.
Drugs like Imdelltra, called T-cell engagers, are established in blood cancers, but their use in solid tumors has been held back by cytokine release syndrome and the monitoring it requires3. Other companies, including AbbVie, Merck, Novartis and Roche, are developing their own drugs aimed at DLL3, according to Fierce Pharma as cited by Credence Research3.
What to watch next
- Regulators: Amgen says it is moving to share the results with regulators worldwide4. In the US, a supplemental filing is needed, and Amgen has not disclosed timing3.
- Longer follow-up: whether the survival gap holds or widens as patients are followed for more years1.
- Practical burden: how hospitals handle the monitoring after the first doses, especially in Europe, where the trial used 6 to 8 hours4.
