Dr Alexander Drilon of Memorial Sloan Kettering Cancer Center recently shared key information during an ALK session about the evolution of ALK-positive lung cancer treatment. For patients in Belgium and beyond, these advances mark an important turning point in the long-term management of the disease.
How do current treatments work?
Most ALK+ patients are familiar with tyrosine kinase inhibitors (TKIs). These medicines work by blocking the “energy opening” (ATP) of the ALK protein, so that cancer cells can no longer multiply. We have come a long way from the first generation (crizotinib) to the second (alectinib, brigatinib) and the third generation (lorlatinib).
The challenge of resistance
Despite the effectiveness of current treatments, the cancer often finds a way to “get around” the medicine. This is what we call resistance. The cancer develops genetic mutations, such as the G1202R mutation, which act like a lock preventing the medicine from binding to the ALK protein. Until now, options after lorlatinib stopped working were limited.
Neladalkib (NVL-655): a new era
Dr Drilon presented data on neladalkib (NVL-655), a fourth-generation TKI designed to address three major challenges:
- Overcoming resistance: it is designed to fit into the ALK protein even when complex mutations are present.
- Activity in the brain: because ALK+ cancer tends to spread to the brain, neladalkib has been developed to cross the blood-brain barrier effectively.
- Fewer neurological side effects: unlike some third-generation treatments, neladalkib avoids blocking TRK receptors in the brain. This reduces the risk of memory problems, mood swings or “brain fog”.
What do the results show?
The ALKOVE-1 study shows very encouraging results. Even in patients who have already been through several treatments, the response is significant. In addition, preliminary results for patients who have never received a TKI are exceptional, with a response rate of almost 90%.
What does the future hold?
A large international study, the ALKAZAR phase 3 trial, is currently under way to compare neladalkib directly with alectinib as a first treatment. The aim is to see whether using the most potent medicine from the outset can offer patients a considerably longer remission.
For Belgian patients it is essential to discuss these new options and ongoing clinical studies with your oncologist. Science is advancing faster than ever and is offering new solutions where previously there were none.