mAb–Drug Therapy Combo Improves NSC Lung Cancer

HOUSTON, TX ― A specific combination of targeted therapy and immunotherapy may better help patients with non-small cell lung cancer (NSCLC) overcome inherent immune resistance and reinvigorate antitumor activity, according to a new study led by a researcher from the University of Texas MD Anderson Cancer Center.  

Results from the Phase 2 umbrella HUDSON study, published recently in Nature Medicine, demonstrated that the anti-PD-L1 antibody, durvalumab, coupled with the ATR kinase inhibitor, ceralasertib, provided the greatest clinical benefit of four combinations evaluated.  

This pair had an objective response rate (ORR) of 13.9 percent compared to just 2.6 percent with the other tested combinations. Median progression-free survival (PFS) was 5.8 months versus 2.7 months for other combinations, while median overall survival (OS) was 17.4 months versus 9.4 months. 

In patients with ATM gene alterations, which should sensitize tumors to ATR kinase inhibitors, the ORR increased to 26.1 percent. Above all, the durvalumab–ceralasertib combination had a manageable safety profile. 

A promising treatment for non-small cell lung cancer 

"Patients with advanced non-small cell lung cancer face significant challenges when standard-of-care treatments fail," said corresponding author John Heymach, MD, PhD, chair of Thoracic/Head & Neck Medical Oncology. "For these individuals, options become limited, emphasizing the urgent need for innovative approaches. Our study represents a promising advancement in addressing this unmet need and holds the potential to offer more effective therapeutic strategies to improve outcomes for this population." 

This study enrolled 268 patients with advanced NSCLC who progressed following standard-of-care therapy. The median age of participants was 63–64 years; 58 percent were male.  

Patients on the trial received one of four targeted therapies: durvalumab in combination with ceralasertib (ATR kinase inhibitor), olaparib (PARP inhibitor), danvatirsen (STAT3-targeting antisense oligonucleotide), or oleclumab (anti-CD73 monoclonal antibody).  

Tumor molecular characteristics were analyzed before treatment, and patients were categorized into biomarker-matched or -unmatched treatment cohorts based on ATM alterations, homologous recombination repair defects, STK11/LKB1 gene alterations, or high CD73 expression.  

Based on the results, durvalumab–ceralasertib is now being tested in a randomized Phase 3 trial for patients with immunotherapy-refractory NSCLC.  

- This press release was originally published on The University of Texas MD Anderson Cancer Center website