Lung Cancer Drugs in Development to Address Resistance Mutations

Nathan Pennell, MD, PhD, vice chair of clinical research and director of lung cancer medical oncology at the Cleveland Clinic Taussig Cancer Center, discusses the importance of developing drugs based on resistance to previous treatments in patients with non–small cell lung cancer (NSCLC).

Pennell’s work on a phase 1 trial (NCT05241834) investigated LOXO-260, an agent designed based on drug resistance to the RET inhibitors selpercatinib (Retevmo) and pralsetinib (Gavreto) for patients with NSCLC and medullary thyroid cancer.

He says that this approach to drug development is based on studying real-world patients who initially respond but then progress on these agents due to resistance mutations. Doing biopsies on these patients for molecular profiling can show whether they have less expression of a gene or new mechanisms of resistance that are not present in untreated patients.

Pennell says that designing new drugs to fit unmet needs of first-generation targeted therapies is an exciting and important part of research, and having a new agent available for patients who relapse is a promising development.

TRANSCRIPTION:

0:08 | These are drugs that basically come directly from information from people with cancer who develop resistance. So real people with advanced lung cancer who are benefiting from targeted treatments, but then [whose] cancer gets worse anyway, have biopsies done, learn what's changed, and then based on that, they have designed drugs to overcome those elements of resistance—the new mutations.

Being able to see that translational bench-to-bedside research is really exciting. To be able to, within a few years of the first drugs being developed, [develop] the next generation of drugs. To be a part of that is really exciting, and hopefully it will help our patients. I think it's a very promising drug and we want to get the word out that it's available so that people out there who need that option can access it.