Targeted therapy and immunotherapy clinical trials

What is targeted therapy?

Targeted therapy is a cancer treatment that destroys cancer cells without harming healthy ones. In practice, oncologists identify specific genetic changes or mutations in your body that turn normal cells into cancer cells, then select treatments that target the specific parts of the cancer cells activated by those genetic abnormalities. Because the treatment is matched to a feature of your cancer rather than to the cancer's location alone, oncologists may call targeted therapy a type of precision medicine^[1].

Cancer starts when something rewrites the genetic instruction book of healthy cells. Following these new genetic instructions is how healthy cells become cancer cells. To use targeted therapy, oncologists typically research the genetic mutation that changes a healthy cell into a cancer cell, decide which parts of the cancer cell to target – the cell surface or substances inside the cell – and use that knowledge to develop a drug that hits those areas. The drug may kill the cells or block the genetic instructions that make the cells multiply^[1].

Because these medicines act on a defined molecular target, their development is usually accompanied by the search for a test that identifies which patients are likely to benefit, known as a biomarker or companion diagnostic test. This is why the same cancer type can be treated with different targeted drugs depending on the genetic changes it carries, and why a drug that works in one patient may not work in another whose tumour lacks the matching target. The practical consequence is that targeted therapy is normally considered only after the tumour has been analysed, not simply on the basis of where the cancer started^[1]. In some cases the matching test is not yet needed, and your specialist can tell you whether it applies to your treatment^[2].

Regulators assess these medicines on the evidence from clinical trials before they can be prescribed. One example is venetoclax, authorised in the European Union under the name Venclyxto. Its variation was assessed by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) and documented in a public assessment report. The report sets out the clinical efficacy and clinical safety data reviewed for that product. Such reports are produced whenever a marketing authorisation is granted or changed. They describe the studies submitted by the company, the questions the assessors raised, and the conclusions reached about the balance between benefit and risk^[3].

What are the main types of targeted therapy?

Oncologists classify targeted therapies by the way they work. There are more than 100 kinds of targeted therapy drugs, and they may be given as a pill you swallow, as a shot, or through an intravenous (IV) line. Treatment schedules vary: you may have treatment every day, weekly or monthly, and sometimes treatment is indefinite while at other times it has a pre-determined duration^[1].

• Small-molecule drugs focus on targets inside cancer cells and disrupt their growth^[1];
• Immunotherapies, including monoclonal antibodies, bispecific antibodies and CAR T-cell therapy^[1];
• Antibody-drug conjugates, which combine an antibody with a toxic payload^[1].

Antibody-drug conjugates are assessed as medicines in their own right. Enfortumab vedotin, authorised in the EU under the name Padcev, is one such product: the CHMP assessment report records its clinical pharmacology, clinical efficacy and clinical safety data. That report also includes immunogenicity data – information about whether the body forms antibodies against the medicine. Immunogenicity is routinely examined because a treatment based on a laboratory-made antibody can itself provoke an immune response. The report notes that the studies followed Good Clinical Practice (GCP), the international standard for how clinical trials are conducted. Because these products combine two mechanisms in a single medicine, assessors review both the antibody component and the attached payload. The clinical data must show that the combination performs as intended^[4].

How does immunotherapy work?

Immunotherapy is a type of cancer treatment that helps your immune system fight cancer. It is made up of white blood cells and organs and tissues of the lymph system, and it is classified as a type of biological therapy – treatment that uses substances made from living organisms^[5].

As part of its normal function, the immune system detects and destroys abnormal cells and most likely prevents or curbs the growth of many cancers. Immune cells are sometimes found in and around tumours; these are called tumour-infiltrating lymphocytes (TILs) and are a sign that the immune system is responding to the tumour. People whose tumours contain TILs often do better than people whose tumours do not contain them^[5].

Cancer cells nevertheless find ways to avoid destruction. They may have genetic changes that make them less visible to the immune system, have proteins on their surface that turn off immune cells, or change the normal cells around the tumour so that those cells interfere with how the immune system responds. Immunotherapy is used to help the immune system act better against cancer^[5]. In the same terms, immunotherapy uses the immune system to fight cancer by helping it recognise and attack cancer cells, and it may be given on its own or with other cancer treatments. It is a standard treatment for some types of cancer and is in clinical trials for others^[2]. Immunotherapy can use your body's immune system to find and destroy cancerous cells, and current immunotherapies cannot cure cancer but may help some people with cancer live longer. Because the treatment depends on the patient's own immune system, the response can continue after the medicine is stopped, and it may take longer to appear than the response to chemotherapy^[6]. It may also be used in combination with other treatments rather than on its own^[2].

What are the types of immunotherapy?

Several types of immunotherapy are used to treat cancer, and they work in different ways^[5]. Some drugs or treatments work in more than one way and belong to more than one group, so you may hear the same drug called different things^[2].

Type	How it works
Immune checkpoint inhibitors	Drugs that block immune checkpoints, which are a normal part of the immune system that keeps immune responses from being too strong; blocking them allows immune cells to respond more strongly to cancer[5].
T-cell transfer therapy	Immune cells are taken from your tumour, the most active ones are selected or changed in the laboratory to attack your cancer better, grown in large batches, and put back into your body through a needle in a vein[5].
Monoclonal antibodies	Immune system proteins created in the laboratory that bind to specific targets on cancer cells; some mark cancer cells so they are better seen and destroyed by the immune system[5].
Treatment vaccines	Boost your immune system's response to cancer cells and are different from vaccines that help prevent disease[5].
Immune system modulators	Enhance the body's immune response against cancer; some affect specific parts of the immune system, others work more generally[5].

Checkpoint inhibitors help immune cells called T cells fight cancer for longer. The body uses checkpoint proteins to manage the signals that tell T cells when to turn on or off, and turning T cells off keeps them from overreacting and damaging healthy cells. These same checkpoints can help cancer cells escape T cells, so immunotherapy drugs stop checkpoint proteins from telling T cells to turn off^[6]. Cancer can sometimes switch off the immune cells so they cannot recognise and attack cancer cells, and checkpoint inhibitors are monoclonal antibodies that work by switching the immune system back on^[2].

Monoclonal antibody therapies mimic natural antibodies but are made in a laboratory; "monoclonal" means all one type, so each therapy is many copies of one type of antibody. They recognise and attach to specific proteins on the surface of cancer cells, and different products work in different ways or in more than one way^[2]. Some monoclonal antibodies block proteins that cancer cells need to grow, others flag cancer cells for destruction, and some inject toxic or radioactive material into cancer cells, killing them. Healthcare providers also consider monoclonal antibody therapy a form of targeted therapy, because it targets cancer cell weaknesses to stop tumours growing^[6]. This overlap explains why the boundary between targeted therapy and immunotherapy is not always sharp. It also explains why the same medicine may be described under either heading depending on which mechanism is being discussed^[2].

What tests come before targeted therapy or immunotherapy?

Before you have some types of immunotherapy, you might need tests using some of your cancer cells or a blood sample. These tests are done to find out whether the treatment is likely to work, and they look for changes in certain proteins or genes. Your cancer specialist can tell you whether this applies to your treatment; it is not the case for all immunotherapies, and you do not always need this test^[2].

To test your cancer cells, your specialist needs a sample of your cancer, called a biopsy. They might be able to use some tissue from a biopsy or an operation you have already had. Whether you can have immunotherapy at all depends on the type of cancer you have, how far it has spread (the stage), and other cancer treatments you have already had^[2].

For targeted therapy, eligibility works the other way round: you may be a candidate if there is a drug available that works against the type of cancer you have. The results of these tests are not simply administrative; they determine which medicine is offered, because a targeted drug is chosen to match a feature that the test has identified in the tumour. If no matching drug exists for the changes found, targeted therapy may not be an option, and your care team will discuss alternatives^[1].

Which cancers are treated with these medicines?

Oncologists commonly use targeted therapy to treat breast cancer, lung cancer and prostate cancer. It may also be a treatment option for blood cancers including multiple myeloma, acute leukaemia and non-Hodgkin lymphoma; bone and soft tissue cancers including some soft tissue sarcomas; common digestive system cancers including colorectal cancer and oesophageal cancer; cancers of the female reproductive system including cervical and endometrial cancer; head and neck cancers including laryngeal and nasopharyngeal cancer; skin cancers such as melanoma and squamous cell carcinoma; thyroid cancers including anaplastic and medullary thyroid cancer; and urinary system cancers such as bladder and kidney cancer^[1].

Immunotherapy drugs have been approved to treat many types of cancer, but immunotherapy is not yet as widely used as surgery, chemotherapy or radiation therapy. To find out whether immunotherapy may be used to treat your cancer, you can look at the PDQ adult and childhood cancer treatment summaries published by the National Cancer Institute^[5].

How are these treatments given?

Different forms of immunotherapy may be given in different ways: intravenously, so the immunotherapy goes directly into a vein; orally, as pills or capsules that you swallow; topically, as a cream you rub onto your skin, which can be used for very early skin cancer; or intravesically, so the immunotherapy goes directly into the bladder. You may receive immunotherapy in a doctor's office, a clinic, or an outpatient unit in a hospital. How often you have it, and how long the course lasts, depends on the type and stage of your cancer, the medicine used, and how well you tolerate it^[5].

During targeted therapy, your cancer care team will schedule regular visits so that your provider can see how you are feeling and check how well your treatment is working. You may have blood tests, X-rays, computed tomography (CT) scans and other tests, and the results show your care team how well the treatment is working. They will also ask how you are doing with any treatment side effects^[1].

What side effects can these treatments cause?

Side effects of targeted therapy vary, but some common ones include bleeding in your stomach or intestines, which may cause changes in your stool such as bright red blood or black tarry stool; blood clots; diarrhoea; dry skin or rash; and elevated liver enzymes^[1].

Immunotherapy can cause side effects, many of which happen when the immune system that has been stimulated to act against the cancer also acts against healthy cells and tissues in your body. Because these reactions can affect healthy tissue, new or worsening symptoms are worth reporting to your care team rather than waiting for your next scheduled visit. Some side effects are common, while others are uncommon but can be serious, so the pattern and timing of symptoms matter when your team decides what to do^[5].

What does taking part in a clinical trial of these medicines involve?

Before a targeted therapy or immunotherapy can be prescribed as a standard treatment, its benefits and risks are examined in clinical trials and assessed by regulators. The European public assessment reports published by the EMA describe exactly this evidence: for venetoclax the report covers clinical efficacy, clinical safety and benefit-risk balance^[3]; for nivolumab it records the development programme, clinical efficacy and clinical safety^[7]; for enfortumab vedotin the report adds that the studies complied with Good Clinical Practice^[4].

Trials also generate the data used to describe how a medicine behaves in the body, such as pharmacokinetics and pharmacodynamics, which appear in the same assessment reports^[3][7]. Regulators also look at how the medicine behaves outside the trial population. A non-interventional study conducted in Germany assessed the effectiveness of atezolizumab under real-world conditions in patients with locally advanced or metastatic non-small cell lung cancer after prior chemotherapy. That study report sets out its research questions and objectives, including effectiveness objectives, safety objectives and other objectives, and records safety variables among the data collected. Such studies collect patient-reported outcome data alongside clinical measures. Non-interventional studies of this kind are complementary to randomised trials, because they observe how a medicine performs in routine care rather than under the controlled conditions of an experiment^[8].

If you are considering a trial, the practical questions are the same whatever the treatment: what is being tested, what will be asked of you, how often you will need to attend, and what happens after the study ends. Ask your specialist whether a trial is suitable for you, what the aim of the treatment would be, what it would involve, and what the side effects are^[2]. Regulators' assessment reports are written for professionals but are public, so reading the report for your medicine can help you understand the evidence behind it^[3][7].

You can look for studies by disease, treatment or location in public registries such as the EU clinical trials register, ClinicalTrials.gov and the WHO ICTRP. Trials recruiting in Europe can also be searched on clinicaltrials.eu. Registries of this kind list the sponsor, the status of recruitment and the eligibility criteria for each study, which makes it possible to see at a glance whether a trial is still enrolling and where it takes place. They are also a way to cross-check what a study team tells you against the publicly registered record of the trial^[2].

When should you contact your care team?

Contact your care team if you develop new or worsening symptoms during targeted therapy or immunotherapy, including bleeding or changes in your stool, blood clots, diarrhoea, or dry skin and rash^[1]. Immunotherapy side effects may arise when the stimulated immune system acts against healthy cells and tissues, so symptoms that appear in parts of the body unrelated to your cancer also need to be reported^[5].

If you are taking part in a clinical trial, tell the study team about every symptom and every other medicine you take, including products you bought without a prescription. Keep the contact details you were given with you, and use them between scheduled visits rather than waiting for the next appointment. Do not stop or change a treatment on your own; discuss it with your care team first. Because the tests used to follow your progress are part of the safety monitoring of the treatment, attending scheduled visits and follow-up appointments matters as much as reporting new symptoms between them^[1].

Summary

Targeted therapy is matched to the genetic changes that drive your cancer, while immunotherapy works by helping your immune system recognise and attack cancer cells. Both are assessed on clinical trial evidence before they become available, and the results – including efficacy, safety and how the medicine behaves in the body – are published in European public assessment reports^[3][4].

If you are considering a trial, three things matter most: ask whether there is a drug that matches your cancer and whether the relevant test is needed; ask what participation would require in terms of visits and tests; and report any new or worsening symptom to your care team as soon as it appears^[2].

1. [1] What Is Targeted Therapy for Cancer? (accessed 02 June 2026) — https://my.clevelandclinic.org/health/treatments/22733-targeted-therapy
2. [2] What is immunotherapy? (accessed 02 June 2026) — https://www.cancerresearchuk.org/about-cancer/treatment/targeted-cancer-drugs-immunotherapy/what-is-immunotherapy
3. [3] Venclyxto - INN: Venetoclax, Variation Assessment Report, EMA/VR/0000322237, Committee for Medicinal Products for Human Use (CHMP) (accessed 02 June 2026) — https://www.ema.europa.eu/en/documents/variation-report/venclyxto-vr-0000322237-epar-assessment-report-variation_en.pdf
4. [4] Padcev - INN: Enfortumab vedotin, Variation Assessment Report, EMA/VR/0000312495, Committee for Medicinal Products for Human Use (CHMP) (accessed 02 June 2026) — https://www.ema.europa.eu/en/documents/variation-report/padcev-vr-0000312495-epar-assessment-report-variation_en.pdf
5. [5] Immunotherapy to Treat Cancer (accessed 02 June 2026) — https://www.cancer.gov/about-cancer/treatment/types/immunotherapy
6. [6] What Is Immunotherapy? (accessed 02 June 2026) — https://my.clevelandclinic.org/health/treatments/11582-immunotherapy
7. [7] Opdivo - INN: Nivolumab, Variation Assessment Report, EMEA/H/C/003985/II/0107, Committee for Medicinal Products for Human Use (CHMP) (accessed 02 June 2026) — https://www.ema.europa.eu/en/documents/variation-report/opdivo-h-c-003985-ii-0107-epar-assessment-report-variation_en.pdf
8. [8] Non-Interventional Study to Assess the Effectiveness of Atezolizumab Under Real-World Conditions in Patients With Locally-Advanced or Metastatic Non-Small Cell Lung Cancer After Prior Chemotherapy [HYPERION], Clinical Study Report No. 1130271 (accessed 02 June 2026) — https://www.pei.de/SharedDocs/Downloads/DE/awb/nis-0401-0500/0439-abschlussb.pdf?__blob=publicationFile&v=1