by A recent clinical trial conducted by researchers at The University of Texas MD Anderson Cancer Center has found that a specific combination of targeted therapy and immunotherapy could significantly improve outcomes for patients with non-small cell lung cancer (NSCLC) who have inherent immune resistance. The results of the Phase II umbrella HUDSON study, published in Nature Medicine, demonstrate that the combination of the anti PD-L1 antibody, durvalumab, with the ATR inhibitor, ceralasertib, provided the greatest clinical benefit among four tested combinations.
The study revealed that the durvalumab-ceralasertib pair achieved an impressive objective response rate (ORR) of 13.9%, in contrast to the other combinations, which only resulted in a 2.6% ORR. Furthermore, the median progression-free survival (PFS) for the durvalumab-ceralasertib combination was 5.8 months, compared to 2.7 months for the other combinations. Median overall survival (OS) was also significantly improved with durvalumab-ceralasertib, with 17.4 months compared to 9.4 months in the other combinations. Notably, in patients with ATM alterations, which should sensitize tumors to ATR inhibitors, the ORR increased to 26.1%. Moreover, durvalumab-ceralasertib exhibited a manageable safety profile.
According to corresponding author John Heymach, M.D., Ph.D., chair of Thoracic/Head & Neck Medical Oncology at MD Anderson, patients with advanced non-small cell lung cancer face significant challenges when standard-of-care therapies fail. For these individuals, treatment options become limited, highlighting the urgent need for innovative approaches. The 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.
The clinical trial enrolled 268 patients with advanced NSCLC who had experienced disease progression following standard-of-care therapy. The median age of participants was 63-64 years, with 58% being male. Patients in the study received one of four targeted therapies in combination with durvalumab: ceralasertib (ATR kinase inhibitor), olaparib (PARP inhibitor), danvatirsen (STAT3 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 alterations, or high CD73 expression.
Based on the promising results, durvalumab plus ceralasertib is currently being evaluated in a randomized Phase III trial for patients with immunotherapy-refractory NSCLC. This trial aims to further validate the efficacy and safety of this combination and potentially provide a new therapeutic option for patients who have had limited success with existing treatments. Ultimately, this groundbreaking research offers hope for improved outcomes and a deeper understanding of immune resistance in lung cancer patients.
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1. Source: Coherent Market Insights, Public sources, Desk research
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