BTOG 2021 | Antibody drug conjugates in lung cancer

So, antibody-drug conjugates are a class of anticancer agent that have actually been around for several years but have not really had a clinical application in lung cancer until recently. So, an antibody-drug conjugate is a type of anticancer drug that consists of three parts; an antibody part that recognizes a target or a protein on the surface of a cancer cell, then a linker molecule that links that antibody to a specialized chemotherapy drug called a cytotoxic payload. An antibody-drug conjugate is a class of agents that has these three parts, an antibody that recognizes a protein or an antigen on the surface of a tumor cell, a linker molecule that links this to a chemotherapy drug and the chemotherapy drug is called a payload and really what’s exciting about these drugs is that these drugs combine the selectivity of an antibody and the potency of a chemotherapy.

So you’re basically bringing the chemotherapy medicines to the cells that match it, to the cancer cells that express these particular proteins. And these drugs have had relevance in other cancer types, such as in breast cancer with the drug T-DM1 that targets HER2 and brentuximab vedotin, which is an antibody-drug conjugate used in Hodgkin’s lymphoma against a marker called CD20.

So in the lung cancer world, we now appreciate that this HER2 marker, which is high in certain patients with breast cancer, may also be high in certain patients with lung cancer, but the HER2 abnormality spans a whole range of different HER2 abnormalities. So having said that, there is a new antibody-drug conjugate against HER2 and one of those is called trastuzumab deruxtecan, and that has been studied in a couple of trials with the backbone name of DESTINY.

So in breast cancer, DESTINY-Breast. In gastric cancer, DESTINY-Gastric and then there was a DESTINY-Lung study, DESTINY-Lung01. And that study showed that this new drug can be helpful in patients who have HER2 aberrations in their lung cancer. And the results were pretty impressive, you know, about 60 to 61% of patients with this subset of lung cancer, HER2-positive lung cancer had shrinkage of their cancers. And over 90% of them had their disease controlled as a result of this agent. So really exciting potential activity and this agent is now being looked at in bigger studies to see if this could help you know more patients or in a different setting.

There are other HER2 and HER3-targeted antibody-drug conjugates. A HER3 one called patritumab deruxtecan and then there are newer targets such as a target called Trop-2 and there are antibody-drug conjugates against Trop-2. And similarly, we have seen an approval for an anti-Trop-2, an antibody-drug conjugate called sacituzumab in triple-negative breast cancer and this looks like it may have activity in types of lung cancer as well, both non-small cell and small cell lung cancer. So really an emerging class of drugs, that appears to have some exciting potential in lung cancer and studies coming to see if this will actually become a new clinical treatment option for our patients.