Dr Naqash on Combining Abequolixron Plus Docetaxel in Recurrent NSCLC

[For] individuals with non–small cell lung cancer [NSCLC], even though we do have very good first-line regimens, the moment those regimens are exhausted and [a patient does not harbor] driver mutations, then the [subsequent treatment] options are very limited. Individuals get [further] into the realm of chemotherapy, which most patients are not excited about.”

Abdul Rafeh Naqash, MD, assistant professor of internal medicine, Phase I Cancer Clinical Trials, Oklahoma TSET Phase I Program, the University of Oklahoma Stephenson Cancer Center, discusses the potential implications of data for the combination of abequolixron (RGX-104)—an oral liver-X receptor agonist—and docetaxel in patients with recurrent, advanced/metastatic NSCLC, highlighting the need for improved treatment options in second- and later-line settings for patients who do not harbor driver mutations.

Data from a phase 1 trial (NCT02922764) presented at the 2024 SITC Annual Meeting showed that evaluable patients treated with the combination (n = 15) achieved an overall response rate (ORR) of 53%. The ORR in the intention-to-treat (ITT) population (n = 21) was 38%. Among the 8 patients who experienced a partial response, the median duration of response was 5.8 months. The median progression-free survival in the ITT population was 3.3 months.

Regarding safety, the most common grade 1/2 treatment-emergent adverse effects (TEAEs) included fatigue (52%), nausea (43%), and diarrhea (38%). The most frequent grade 3 or higher TEAEs comprised neutropenia (14%), fatigue (10%), nausea (10%), and dyspnea (10%).

Since chemotherapy does have an established role in later-line settings for patients with recurrent, advanced/metastatic NSCLC, investigating ways to expand on the benefit provided by chemotherapy in these settings is a logical step, Naqash explains. Adding an “immune modulator” like abequolixron could help balance out AEs that patients commonly experience when treated with chemotherapy, he adds. Additional later-line treatment options are needed for patients with advanced NSCLC in order to improve both survival and quality of life, he concludes.

A planned phase 2 randomized study will further investigate abequolixron plus docetaxel in patients with recurrent advanced or metastatic NSCLC who previously received treatment with an immune checkpoint inhibitor and platinum-based chemotherapy.