The treatment of lung cancer has changed dramatically over the past two decades. Targeted therapies revolutionised outcomes for patients with specific driver mutations such as EGFR, ALK and ROS1. Immunotherapy transformed the approach to patients without targetable alterations. Now, a newer class of treatment — antibody-drug conjugates — is beginning to reshape the landscape once more, including for patients whose cancers have progressed despite earlier targeted therapies or immunotherapy.
Dr Dionysis Papadatos-Pastos, a consultant medical oncologist specialising in lung cancer in London and an active clinical researcher in targeted therapies, explains what antibody-drug conjugates are, how they work, and what they may offer to patients with lung cancer.
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Topics CoveredWhat Is an Antibody-Drug Conjugate?
An antibody-drug conjugate — often referred to as an ADC — is a type of cancer treatment that combines two components:
- a monoclonal antibody, which is designed to seek out and bind to a specific target on the surface of cancer cells
- a cytotoxic payload — a potent chemotherapy agent — that is chemically attached to the antibody
The antibody acts as a highly precise delivery vehicle, carrying the chemotherapy directly to the tumour cell. Once the antibody binds to its target on the cancer cell surface, the complex is taken up into the cell, where the cytotoxic payload is released and destroys the cell from within.
The principle is sometimes described as a “targeted missile” — the guidance system is the antibody, and the warhead is the chemotherapy. Because the payload is delivered directly to cancer cells rather than distributed throughout the body, ADCs aim to maximise anti-tumour activity while reducing the systemic side effects associated with conventional chemotherapy.
Why ADCs Are Particularly Relevant in Lung Cancer
Despite the advances brought by targeted therapies and immunotherapy, many patients with non-small cell lung cancer eventually develop resistance to their initial treatment. Others have tumours that do not carry targetable mutations and have limited response to immunotherapy. For these patient populations, new treatment approaches are needed.
ADCs have emerged as an important option in this context. They can be active against tumours regardless of driver mutation status, and several ADCs have demonstrated meaningful responses in patients who have progressed after multiple prior lines of treatment.
In addition, lung cancer cells express several surface proteins — including HER2, HER3, TROP2 and others — that can serve as targets for ADC-based therapies. This makes lung cancer a particularly active area of ADC development.
Key ADCs in Lung Cancer
Trastuzumab Deruxtecan (T-DXd)
Trastuzumab deruxtecan, known by the brand name Enhertu, is an ADC that targets HER2 — a protein found on the surface of some lung cancer cells. HER2 alterations in lung cancer include mutations and, less commonly, amplification or overexpression.
Trastuzumab deruxtecan has demonstrated impressive response rates in patients with HER2-mutant NSCLC, a population that historically had very limited targeted treatment options. It has received regulatory approval for this indication and represents one of the most significant advances in HER2-targeted therapy in lung cancer.
Patritumab Deruxtecan (HER3-DXd)
Patritumab deruxtecan is an ADC targeting HER3, a protein that is broadly expressed in NSCLC. Because HER3 expression is widespread across different lung cancer subtypes — including in tumours that have developed resistance to EGFR inhibitors — this agent has the potential to benefit a wide range of patients.
Clinical trial data have shown meaningful responses in patients with EGFR-mutant NSCLC whose disease has progressed after osimertinib, a setting where treatment options are currently limited. Regulatory review is ongoing.
Datopotamab Deruxtecan (Dato-DXd)
Datopotamab deruxtecan targets TROP2, a protein expressed across a broad range of NSCLC subtypes. It is being evaluated in multiple settings, including in patients with and without driver mutations, and in combination with other agents.
Early clinical data have shown activity in NSCLC, and further trials are underway to define its role more precisely in the treatment sequence.
How ADCs Differ From Conventional Chemotherapy
Conventional chemotherapy acts throughout the body, affecting both cancerous and healthy rapidly dividing cells. This broad mechanism accounts for many of the familiar side effects of chemotherapy, including hair loss, nausea, fatigue and bone marrow suppression.
ADCs are designed to concentrate their activity at the tumour site, which in principle should reduce off-target toxicity. In practice, ADCs do have side effects — and some side effects are specific to this class of treatment, such as interstitial lung disease, which requires careful monitoring. However, the toxicity profile is different from conventional chemotherapy, and many patients tolerate ADCs well.
It is also important to note a phenomenon known as the “bystander effect” — when the cytotoxic payload is released inside a targeted cancer cell, it can also affect neighbouring tumour cells that may not express the target at high levels. This can extend the anti-tumour activity of ADCs beyond the cells to which they directly bind.
ADCs and Treatment Resistance
One of the most clinically important applications of ADCs in lung cancer is in the setting of treatment resistance. Patients who develop resistance to first-line targeted therapies — for example, after osimertinib in EGFR-mutant NSCLC — often have limited options.
ADCs targeting HER3 and other proteins expressed in resistant tumours are being studied precisely in this context, and early data suggest meaningful activity. This makes ADCs a potentially important part of the treatment landscape for patients who have exhausted earlier lines of treatment.
The Role of Biomarker Testing in ADC Treatment
Some ADCs require specific biomarker testing to determine eligibility — for example, HER2 mutation testing before trastuzumab deruxtecan in NSCLC. Others, like patritumab deruxtecan, may be active across patients regardless of HER3 expression level, though testing may still inform treatment decisions.
Comprehensive molecular profiling at diagnosis and at progression is therefore important not only for identifying driver mutations but also for understanding which ADC-based therapies may be appropriate at different stages of treatment.
Access to ADC Therapies: Clinical Trials and Private Care
Not all ADC therapies are yet licensed for routine use in the UK. Some are available through clinical trials, others through managed access programmes, and a small number have received formal regulatory approval.
For patients who may be eligible for ADC-based treatment, specialist input is essential. Dr Papadatos-Pastos, as Lung Cancer Lead at the CRUK UCL Clinical Trials Centre, works closely with clinical research networks and is well positioned to identify relevant trial opportunities. Private specialist care also offers the opportunity to explore all available options — including emerging therapies — without delay, and with the dedicated consultation time needed to understand the implications fully.
Conclusion
Antibody-drug conjugates represent a genuinely new generation of targeted cancer treatment. By combining the precision of antibody targeting with the potency of cytotoxic chemotherapy, they offer a mechanism that is distinct from both conventional chemotherapy and traditional targeted therapies — and are showing meaningful activity in settings where other treatments have been exhausted.
In lung cancer, ADCs are already changing outcomes for selected patient populations, and their role is likely to expand significantly as further clinical trial data emerge. For patients whose lung cancer has progressed after prior treatment, or who wish to understand all available options including emerging therapies, a private specialist consultation can provide an expert and up-to-date review of the treatment landscape.
If you would like to discuss antibody-drug conjugates or other advanced treatment options for lung cancer, Dr Papadatos-Pastos sees patients privately at several London clinics and is available for 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 ask about newer treatments for lung cancer, including antibody-drug conjugates. The following answers explain the key concepts in plain language.
An antibody-drug conjugate (ADC) is a cancer treatment that combines a targeted antibody — designed to seek out specific proteins on cancer cell surfaces — with a potent chemotherapy drug. The antibody delivers the chemotherapy directly to cancer cells, aiming to maximise anti-tumour activity while reducing the broader side effects of conventional chemotherapy.
Several ADCs are now being used or evaluated in lung cancer, including trastuzumab deruxtecan (targeting HER2), patritumab deruxtecan (targeting HER3) and datopotamab deruxtecan (targeting TROP2). The most appropriate agent depends on the molecular profile of the tumour and the stage of treatment.
Standard chemotherapy acts throughout the body and affects both cancer cells and healthy rapidly dividing cells, which accounts for many of its familiar side effects. ADCs are designed to concentrate their activity at the tumour site by delivering chemotherapy directly to cells expressing a specific target protein, which can alter the side effect profile compared with conventional treatment.
For some ADCs, yes. Trastuzumab deruxtecan, for example, requires confirmation of HER2 alteration in the tumour. Comprehensive molecular profiling is therefore important not only for identifying initial treatment options but also for understanding which ADC therapies may be appropriate as treatment evolves.
Some ADCs have received regulatory approval and are available in the UK, including through the NHS and privately. Others are currently available through clinical trials or managed access programmes. A specialist consultation can help clarify which options are accessible based on individual circumstances.
ADCs are being studied specifically in patients whose lung cancer has progressed after prior targeted therapies, including EGFR inhibitors. Early clinical data suggest meaningful activity in this setting, and this is one of the most active areas of ADC research in NSCLC.
ADC side effects differ from those of conventional chemotherapy and vary by agent. One side effect that requires monitoring with several ADCs is interstitial lung disease — inflammation in the lungs — which can occur in a small proportion of patients. Other side effects may include nausea, fatigue and low blood counts. A specialist will discuss the specific side effect profile relevant to any proposed ADC treatment.
Yes. Clinical trials evaluating ADCs in lung cancer are active, and eligibility depends on the molecular profile of the tumour, prior treatment history and clinical circumstances. Dr Papadatos-Pastos, as Lung Cancer Lead at the CRUK UCL Clinical Trials Centre, is well placed to identify relevant trial opportunities for eligible patients.
