Small cell lung cancer often responds well to its first treatment, but in many people it comes back. For a long time, the options at that point were limited and mostly based on chemotherapy. Tarlatamab has changed this picture. It is the first treatment designed to target a protein called DLL3, which is found on the surface of most small cell lung cancer cells, and it works by directing the body’s own immune cells towards the cancer.
For patients and families, a new treatment brings hope but also many questions: how it works, who it is for, what treatment involves and whether it is available in the UK.
Dr Dionysis Papadatos-Pastos, a consultant medical oncologist in London specialising in lung cancer, mesothelioma and thymic tumours, explains what tarlatamab is, what the research shows and what patients can expect.
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When Small Cell Lung Cancer Returns
Small cell lung cancer (SCLC) tends to grow quickly, and in most people it has already spread beyond the chest when it is diagnosed. This is known as extensive-stage disease. First treatment usually combines chemotherapy with immunotherapy, and many people respond well. Our article can small cell lung cancer be cured explains the stages of SCLC and what treatment can achieve.
Unfortunately, the cancer often returns, sometimes within months. When this happens, the choice of further treatment depends on how long the first response lasted, how a person is feeling and what treatment they have already had. Until recently, this mostly meant a different chemotherapy, which helped some people but often for a short time. This is why the arrival of tarlatamab has been an important step.
What Is DLL3?
DLL3 (delta-like ligand 3) is a protein found on the surface of most small cell lung cancer cells. Healthy cells have very little or none of it on their surface. This difference makes DLL3 a useful target: a treatment aimed at DLL3 can recognise cancer cells while largely leaving healthy tissue alone.
Unlike many treatments for non-small cell lung cancer, tarlatamab does not require a specific test before treatment. DLL3 is present in most small cell lung cancers, and the UK licence does not depend on testing for it. Your oncologist will explain whether any further tests are needed in your situation.
How Tarlatamab Works
Tarlatamab belongs to a group of treatments called bispecific T-cell engagers. Its name describes what it does. One end of the molecule attaches to DLL3 on the cancer cell. The other end attaches to a protein called CD3 on T cells, the immune cells that can destroy abnormal cells. By holding the two together, tarlatamab acts like a bridge that brings the T cell right next to the cancer cell, so that the immune system can attack it.
This is different from the immunotherapy drugs used in first treatment, such as atezolizumab or durvalumab. Those drugs release a “brake” on the immune system in general. Tarlatamab instead points the immune cells directly at a target on the cancer. Our article on novel therapies in small cell lung cancer describes this and other new approaches.
What the Research Shows
Tarlatamab was first studied in people whose small cell lung cancer had come back after at least two earlier treatments. In the DeLLphi-301 study, around four in ten people saw their cancer shrink, and for many of them the response lasted for several months or longer.
The larger DeLLphi-304 study, published in 2025, compared tarlatamab with standard chemotherapy in 509 people whose cancer had come back after first treatment with platinum-based chemotherapy. People who received tarlatamab lived longer on average: median survival was 13.6 months with tarlatamab and 8.3 months with chemotherapy. They also had fewer serious side effects than people treated with chemotherapy, and many reported better control of symptoms such as breathlessness and cough.
These figures are averages from a clinical trial and describe a whole group, not a single patient. Some people respond for much longer, and others do not respond. A specialist can explain what the results may mean in your own situation.
Who May Be Suitable for Tarlatamab
Tarlatamab is used for adults with small cell lung cancer that has grown or come back during or after platinum-based chemotherapy. It is not currently used as a first treatment outside clinical trials.
Whether it is the right choice depends on several things: general health and fitness, other medical conditions, how the cancer has behaved so far and a person’s own wishes. Because the first doses need close monitoring, it also matters that someone can stay near the hospital at the start of treatment, with a family member or friend.
These decisions are best made by a specialist multidisciplinary team (MDT) with experience of small cell lung cancer. Our guide to first-line and second-line treatment explains how treatment is planned when cancer returns.
Access to Tarlatamab in the UK
In the UK, tarlatamab (brand name Imdylltra) is licensed by the Medicines and Healthcare products Regulatory Agency (MHRA) for adults with small cell lung cancer that has progressed on or after platinum-based chemotherapy. It also has full approval from the US Food and Drug Administration (FDA) and approval in the European Union.
Being licensed is not the same as being routinely available on the NHS. In England, the National Institute for Health and Care Excellence (NICE) did not recommend tarlatamab in 2025 for people who had already had two or more treatments (NICE TA1091), mainly because of its cost. NICE is now assessing tarlatamab for use after first treatment with platinum-based chemotherapy, with a decision expected in early 2027.
Tarlatamab is available privately in the UK, and it may also be available within clinical trials. If you would like to know whether tarlatamab could be an option for you, it is reasonable to ask your oncologist directly.
How Treatment Is Given
Tarlatamab is given as a drip into a vein (an intravenous infusion) that takes about an hour. Treatment starts with a lower dose on the first day, followed by the full dose a week later and again a week after that. From then on, it is usually given every two weeks for as long as it is helping and side effects remain manageable.
The first two doses need the most care, because this is when side effects are most likely. In practice:
- you are given medicine and fluids beforehand to reduce the risk of reactions
- after the first dose, you stay in hospital for monitoring, usually overnight
- after the second dose, you are monitored for several hours
- for the first 24 hours after each of these doses, you are asked to stay within an hour of the hospital, with a family member or friend
- later doses are given as a day treatment, with a shorter period of observation
It is advisable not to drive or operate machinery for a while after the early doses. The care team will explain what this means for you.
Side Effects and How They Are Managed
Because tarlatamab activates the immune system, its side effects are different from those of chemotherapy.
The most common is cytokine release syndrome (CRS), a reaction caused by the activated immune cells. It can cause fever, chills, tiredness, a fast heartbeat, low blood pressure or low oxygen levels. CRS happens in around half of people, most often after the first or second dose, and in most cases it is mild and settles with treatment. This is the main reason for the close monitoring at the start.
Less often, the immune activation can affect the nervous system. This is called ICANS (immune effector cell-associated neurotoxicity syndrome). Signs can include confusion, difficulty finding words, unusual sleepiness, shaking or changes in handwriting. Family members are often the first to notice these changes, which is why they are given information too.
Other common side effects include a change in taste, reduced appetite, constipation, tiredness and low blood counts.
It is important to contact the care team straight away about any fever, feeling faint, breathing difficulty, confusion or other new symptoms. Most side effects can be managed well when they are recognised early, and treatment can often continue.
Ongoing Research With Tarlatamab and DLL3
Research is moving quickly. Studies are looking at whether tarlatamab can help earlier in the course of the disease. In September 2026, early results from the DeLLphi-305 study were announced, showing that adding tarlatamab to durvalumab after first treatment helped people live longer than durvalumab alone. This use is still being studied and is not yet approved.
Other studies are testing tarlatamab after chemoradiotherapy for limited-stage small cell lung cancer, and a version given as an injection under the skin. New treatments aimed at DLL3, including other T-cell engagers and antibody-drug conjugates, are also in development. Clinical trials remain an important option for many people with small cell lung cancer, and the NIHR Be Part of Research website lists studies open in the UK.
Why Specialist Experience Matters
Tarlatamab is a powerful treatment, and its early doses need a team that knows how to recognise and manage CRS and ICANS quickly. The UK licence states that treatment should be started and supervised by doctors experienced in treating small cell lung cancer.
At The London Clinic, Dr Papadatos-Pastos and his team were the first in the UK independent sector to offer tarlatamab to eligible patients, with dedicated monitoring arrangements for the early doses.
A private specialist consultation offers time to talk through whether tarlatamab or another option is right for you, a second opinion on a treatment plan and input from a multidisciplinary team. It can also work alongside NHS care. Preparing a few questions to ask your oncologist can help you make the most of each appointment.
Conclusion
Tarlatamab is an important advance for people whose small cell lung cancer has come back after chemotherapy. By targeting DLL3 and bringing the immune system to the cancer, it has helped people live longer than chemotherapy, with side effects that are usually manageable in experienced hands. Research is now exploring its use earlier in treatment.
If you or someone close to you has small cell lung cancer and would like to discuss tarlatamab or other treatment options, Dr Papadatos-Pastos sees patients privately at several London clinics and offers both in-person and virtual consultations.
Support and Follow-Up Care
Dr Papadatos-Pastos and his team provide ongoing support beyond medical treatment.
Patients receive clear communication, psychological care and access to nutrition, physiotherapy and symptom-management services.
Regular follow-up ensures early detection of recurrence and long-term wellbeing.
Book a Consultation
If you or someone close to you has been diagnosed with lung cancer, early consultation with a specialist can make a real difference. Appointments are available at several London clinics.
Faq
Answers to Common Questions
Patients and families often have questions about tarlatamab and what treatment involves. Here are short answers to the questions we hear most often.
Tarlatamab (Imdylltra) is a treatment for small cell lung cancer that has come back or grown after platinum-based chemotherapy. It is a bispecific T-cell engager: it attaches to a protein called DLL3 on cancer cells and to T cells of the immune system, bringing them together so that the immune system can attack the cancer.
DLL3 is a protein found on the surface of most small cell lung cancer cells but very little on healthy cells. Because it is present in most small cell lung cancers, a DLL3 test is not required before treatment with tarlatamab. Your oncologist will explain whether any other tests are needed.
Tarlatamab is used for adults with small cell lung cancer that has progressed during or after platinum-based chemotherapy. Suitability depends on general health, other medical conditions and personal preferences, and is best decided by a specialist team experienced in small cell lung cancer.
Tarlatamab is licensed in the UK, but it is not currently routinely available on the NHS in England. NICE did not recommend it in 2025 for people who had already had two or more treatments, and it is now assessing its use after first chemotherapy, with a decision expected in early 2027. Tarlatamab is available privately and may be available within clinical trials.
Tarlatamab is given as a one-hour drip into a vein, with a lower first dose, then the full dose a week later and every two weeks after that. After the first dose, patients usually stay in hospital overnight for monitoring. After the first two doses, they are asked to stay within an hour of the hospital for 24 hours, with a family member or friend.
The most common side effect is cytokine release syndrome, which can cause fever, chills and low blood pressure, mostly after the first or second dose and usually mild. Less often, it can affect the nervous system, causing confusion or shaking. Other common effects include taste changes, reduced appetite, constipation and tiredness. Any fever or new symptom should be reported to the care team straight away.
Yes, but it works differently from the immunotherapy drugs used in first treatment for small cell lung cancer. Those drugs release a general brake on the immune system. Tarlatamab directs immune cells specifically to DLL3 on cancer cells.
Not yet outside clinical trials. Studies are looking at tarlatamab earlier in treatment, including after first chemotherapy and immunotherapy, and early results announced in September 2026 were encouraging. This use is not yet approved in the UK.
