UMBRELLA of hope unfolds: biomarker-driven combination therapy works in immunoresistant NSCLC

UMBRELLA of hope unfolds: biomarker-driven combination therapy works in immunoresistant NSCLC

A study published today in Nature Medicine highlights how the use of biomarkers to guide targeted therapy combined with immunotherapy in advanced non-small-cell lung cancer (NSCLC) can overcome resistance to previous immunotherapy-based treatment. This finding is a major step forward in reinvigorating anti-tumour activity in patients who did not respond to anti-PD-L1-containing immunotherapy and platinum-doublet therapy. The phase II umbrella HUDSON trial showed that the anti-PD-L1 antibody durvalumab combined with the ATR inhibitor, ceralasertib, provided the greatest clinical benefit among four possible combinations of immunotherapy and targeted therapies. The objective response rate (ORR, the primary outcome) was 13.9% (11/79) compared with only 2.6% (5/189) for the other combinations. Pooled analysis of the median progression-free survival was 5.8 months for durvalumab–ceralasertib versus 2.7 months for the other dual PD-L1 combinations, which included olaparib, danvatirsen or oleclumab. Median overall survival was 17.4 months versus 9.4 months. The durvalumab–ceralasertib combination benefit was noted across all known immunotherapy-refractory subgroups. In patients with ATM alterations, who were expected to be vulnerable to ATR inhibitors such as ceralasertib, the ORR increased to 26.1%. Patients with advanced NSCLC have few options when standard therapy fails. John Heymach, lead author of the study notes stated: “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.”

READ THE ARTICLE – https://www.eurekalert.org/news-releases/1034203

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