TROP2 and lung cancer: what we know so far
TROP2 appears often in lung cancer research news at the moment. This post explains what it is, what the trials have found, and what is approved in Europe.
What is TROP2?
TROP2 is a protein found on the surface of many epithelial cells. It is often present at higher levels in solid tumours, including many non-small cell lung cancers.
This difference makes TROP2 useful as a target. A drug can be designed to find cells carrying more of it.
What drugs target it?
The main ones are antibody-drug conjugates, usually shortened to ADCs.
An ADC has three parts:
An antibody that recognises TROP2 and attaches to it
A chemotherapy drug, called the payload
A linker that holds the two together
After the ADC attaches to the cell, it is usually taken inside, where it releases its payload. Some payload can also affect nearby tumour cells.
The aim is to deliver chemotherapy to tumour cells while sparing healthy tissue. These drugs are still chemotherapy. The difference is in how it is delivered.
Three TROP2 ADCs are approved somewhere in the world:
Sacituzumab govitecan
Datopotamab deruxtecan (brand name Datroway)
Sacituzumab tirumotecan
All three use payloads from the topoisomerase I inhibitor family, but they differ in their antibody, their linker, their payload and the amount of drug attached to each antibody. Several other TROP2 ADCs are also being studied in lung cancer.
What have the trials found?
Results are mixed.
TROPION-Lung01 compared datopotamab deruxtecan with docetaxel in people who had already had treatment. The drug delayed cancer growth slightly: 4.4 months compared with 3.7 months. More people responded to it: 26.4% compared with 12.8%. The trial did not show a statistically significant improvement in overall survival, which was 12.9 months compared with 11.8 months. The benefit was seen mainly in people with non-squamous lung cancer. People with squamous lung cancer did worse on the ADC than on docetaxel.
EVOKE-01 compared sacituzumab govitecan with docetaxel. It did not meet its main goal. Overall survival was 11.1 months compared with 9.8 months, which did not reach statistical significance.
OptiTROP-Lung04 studied sacituzumab tirumotecan in people with non-squamous, EGFR-mutant lung cancer whose EGFR treatment had stopped working. This trial was positive. Cancer growth was delayed for 8.3 months compared with 4.3 months on chemotherapy, and people also had significantly longer overall survival. The results were published online in the New England Journal of Medicine in October 2025.
OptiTROP-Lung06 In July 2026, Kelun-Biotech announced that this trial had met its progression-free survival endpoint. It compared sacituzumab tirumotecan plus pembrolizumab with chemotherapy plus pembrolizumab, in people with previously untreated, PD-L1-negative, non-squamous lung cancer. Numerical results have not yet been published, so the size of the benefit is not known.
Does the amount of TROP2 predict who benefits?
Not in a straightforward way.
Standard laboratory tests measure how much TROP2 is present. Using those tests, the amount did not predict who did well.
A newer computational test looks not only at how much TROP2 is present, but at how it is distributed between the cell membrane and the inside of the cell. In an exploratory analysis of TROPION-Lung01, this pattern appeared to identify people more likely to benefit from datopotamab deruxtecan. People who tested positive had cancer growth delayed for 7.2 months, compared with 4.1 months on docetaxel. People who tested negative saw no benefit.
This analysis was carried out after the trial, and the test and its threshold were developed using trial data. It is not yet a validated routine test.
A trial called TROPION-Lung17 is now testing the approach directly, by enrolling only people who test positive using this biomarker.
What are the side effects?
Side effects vary between the different TROP2 ADCs.
Mouth inflammation and eye surface problems, such as dry or gritty eyes, are particularly associated with datopotamab deruxtecan. Low neutrophil counts and diarrhoea are more prominent with sacituzumab govitecan. Nausea, tiredness and low blood counts are seen across the group.
Preventive mouth and eye care, close monitoring and early treatment may reduce the severity of these effects and help people stay on treatment.
Interstitial lung disease and pneumonitis are an uncommon but potentially serious risk. Interstitial lung disease means inflammation of the lung tissue, which can sometimes become severe or lead to scarring. In TROPION-Lung01, adjudicated drug-related interstitial lung disease or pneumonitis occurred in 26 people (8.8%) receiving datopotamab deruxtecan, including seven grade 5 events (2.4%). The investigators assessed the primary cause of death as disease progression in four of those seven cases.
What is approved in Europe?
No TROP2 antibody-drug conjugate is currently approved in the EU for lung cancer.
Datroway is authorised in the EU for breast cancer, but not lung cancer. In June 2026, the EMA's Committee for Medicinal Products for Human Use recommended a further Datroway indication for the first-line treatment of certain adults with unresectable or metastatic triple-negative breast cancer. This was not a lung cancer indication, and a final European Commission decision is still required.
Sacituzumab tirumotecan is approved in China.
In June 2025, the FDA granted Datroway accelerated approval in the United States for adults with locally advanced or metastatic EGFR-mutated non-small cell lung cancer who had previously received an EGFR-directed treatment and platinum-based chemotherapy.
ESMO's living guideline for oncogene-addicted metastatic non-small cell lung cancer says datopotamab deruxtecan may be considered after progression on an EGFR TKI and platinum-based doublet chemotherapy. The recommendation is graded III, B and the treatment has an ESMO-MCBS benefit score of 2. The guideline also makes clear that it is FDA approved but not EMA approved.
A treatment can therefore be included in a clinical guideline even though it does not yet have an EU marketing authorisation for that use.
Where this goes next
Several phase 3 trials are running. The main open questions are whether improvements in progression-free survival will translate into longer overall survival, and when, or whether, these drugs will be approved in Europe for lung cancer.
Another important question is whether TROP2 testing itself will become part of routine care, if ongoing studies confirm that it can identify the people most likely to benefit.
Sources
National Cancer Institute. Antibody Drug Conjugates (ADCs). https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/antibody-drug-conjugates
Ahn MJ, Tanaka K, Paz-Ares L, et al. Datopotamab Deruxtecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non Small Cell Lung Cancer: The Randomized Open Label Phase III TROPION Lung01 Study. Journal of Clinical Oncology. 2025;43:260–272. DOI: 10.1200/JCO-24-01544.
Bardia A, et al. EVOKE-01: Sacituzumab Govitecan Versus Docetaxel in Previously Treated Metastatic Non Small Cell Lung Cancer. Journal of Clinical Oncology. DOI: 10.1200/JCO.24.00733.
Zhou C, et al. Sacituzumab Tirumotecan Versus Chemotherapy in EGFR Mutated Advanced Non Small Cell Lung Cancer (OptiTROP Lung04). New England Journal of Medicine. Published online 19 October 2025. DOI: 10.1056/NEJMoa2512071.
Kelun Biotech. OptiTROP Lung06 met its primary endpoint. Company announcement, July 2026.
IASLC. Normalized membrane ratio TROP2 computational biomarker analysis from TROPION Lung01.
European Medicines Agency. Datroway European Public Assessment Report (EPAR).
European Medicines Agency. CHMP positive opinion: Datroway variation for triple negative breast cancer. June 2026.
US Food and Drug Administration. FDA grants accelerated approval to datopotamab deruxtecan for EGFR mutated NSCLC. 23 June 2025.
European Society for Medical Oncology. ESMO Living Guideline: Oncogene addicted metastatic non small cell lung cancer.
ClinicalTrials.gov. TROPION Lung17. NCT06702735.