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 

 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.

Videos

Abdul Rafeh Naqash, MD, discusses the potential role for abequolixron plus docetaxel in recurrent advanced non–small cell lung cancer.

Abdul Rafeh Naqash, MD, advanced fellow, Early Clinical Trials Development Program, National Cancer Institute, discusses the results of a tumor profiling study in 

 co-mutated non–small cell lung cancer (NSCLC). 

, findings from an analysis were presented that demonstrated that patients with NSCLC who harbor 

 co-mutations have more immunologically active tumor microenvironments with metabolic reprogramming compared with 

Of 16,896 NSCLC samples, 12.6% of patients harbored an 

 mutations had the proportions of tumor mutation burden (TMB)–high (10 or more mutations per megabase) disease, 11.8% were PD-L1 positive (50% or greater by 22C3 antibody testing), and 0.72% were microsatellite instability high, Naqash explains. 

No differences were observed comparing TMB between the 

 led to higher median TMB and neoantigen load compared with 

Abdul Rafeh Naqash, MD, discusses the results of a tumor profiling study in STK11 and TP53 co-mutated non–small cell lung cancer. 



Dr. Naqash on the Results of a Tumor Profiling Study in STK11/TP53 Co-Mutated NSCLC 

Abdul Rafeh Naqash, MD, an advanced fellow in the Early Clinical Trials Development Program and the Developmental Therapeutics Clinic at the National Cancer Institute, and Alice Chen, MD, head of the Early Clinical Trials Development Program and Developmental Therapeutics Clinic, at the National Cancer Institute, discuss the phase 2 trial evaluating the efficacy of atezolizumab (Tecentriq) in patients with advanced alveolar soft part sarcoma.

As of April 2021, 46 of 53 patients have been enrolled on a phase 2 trial (NCT03141684) studying the agent, 45 of whom have already received treatment, according to Naqash. Investigators reported an objective response rate of 37.2%, with a median duration of confirmed response of 16.6 months, and a median time to confirmed response of 3.5 months.

Interestingly, 3 patients who had been on a treatment holiday as per protocol had maintained their partial responses for a median duration of 8.6 months. These evaluations suggest that atezolizumab has promising clinical activity in patients with alveolar soft part sarcoma, Naqash says.

Future direction will focus on the addition of bevacizumab (Avastin) as an anti-angiogenesis agent in patients who have progressed on atezolizumab, according to Chen. Additionally, previous reports have indicated that a combination of pembrolizumab (Keytruda) and axitinib (Inlyta) have demonstrated promising activity in this patient population. Moreover, bevacizumab and atezolizumab have been examined in other histologies, such as hepatocellular carcinoma, with positive results, Chen says.

The combination is currently being examined in patients with alveolar soft part sarcoma in order to overcome resistance to atezolizumab, as the anti-angiogenesis component of bevacizumab could change the microenvironment and immunotherapy effect, Chen concludes.

Abdul Rafeh Naqash, MD, and Alice Chen, MD, discuss their phase 2 trial evaluating the efficacy of atezolizumab in patients with advanced alveolar soft part sarcoma.

Abdul Rafeh Naqash, MD

Articles

Dr Naqash on Combining Abequolixron Plus Docetaxel in Recurrent NSCLC

Dr. Naqash on the Results of a Tumor Profiling Study in STK11/TP53 Co-Mutated NSCLC

Dr. Naqash and Dr. Chen on the Efficacy of Atezolizumab in Advanced Alveolar Soft Part Sarcoma