Finding the right clinical trial can be challenging, especially as new treatment options for RET fusion-positive lung cancer continue to emerge. This tool was created to help patients and caregivers, quickly identify clinical trials that may be appropriate based on a patient’s treatment history and tumor characteristics.
Importantly, if your cancer has progressed while taking a RET inhibitor, we strongly encourage you to discuss repeat molecular testing (using a tissue biopsy and/or liquid biopsy) with your oncology team. Identifying the specific mechanism of resistance, such as a RET resistance mutation or a bypass alteration like MET amplification, may help determine which clinical trials you may be eligible for and guide the next phase of treatment.
The trials are organized into three main categories:
1. Clinical Trials of Next-Generation RET Inhibitors
These studies are evaluating newly developed RET inhibitors designed to inhibit the RET molecule. In most cases these compounds are also effective targeting RET resistance mutations like RET G810 solvent-front mutations. Tumor sequencing at progression is important to determine the presence of RET resistance mutations or other mechanisms of resistance like RET bypass alterations.
2. Clinical Trials Testing Cancer Vaccines
These studies are investigating novel cancer vaccines including therapeutic mRNA vaccines, that aim to stimulate the immune system to recognize and attack RET-positive lung cancer cells.
3. Clinical Trials for Patients Who Have Progressed on RET Inhibitors
For patients whose cancer has developed resistance to a RET inhibitor through bypass mechanisms (such as MET amplification) or other co-occurring genetic alterations, these trials are evaluating therapies that target these specific resistance pathways.
IMPORTANT: Many of these studies evaluate the investigational drug as a single agent and do not include continued treatment with a RET inhibitor in combination.
In a situation where a RET patient developed resistance to a RET inhibitor through a bypass mechanisms, some oncologists may consider continuing the RET inhibitor while adding a second therapy directed at the newly activated resistance pathway. The goal is to continue suppressing the RET-driven cancer while simultaneously blocking the bypass mechanism that is allowing the tumor to escape treatment.
Because it has not yet become a standard treatment strategy this combination approach is often not available within these clinical trials, but these studies may help identify drugs that target your specific resistance mechanism. You can discuss with your oncologist whether an off-label combination approach with these agents or another treatment strategy may be appropriate for your individual situation.
