Gene- and immune-targeted therapy combinations using dual-matched biomarkers for patient selection

Combinations of gene-targeted therapy and immune checkpoint inhibitors (ICIs) have been conducted, though generally without biomarker-based patient selection for both therapy types. We evaluated outcomes of 17 patients with advanced cancers treated with both targeted agents and ICIs, matched to distinct genomic and immune biomarkers, from a cohort of 715 cases discussed at our Molecular Tumor Board. Despite 29% of patients having undergone ≥3 prior therapies, the disease control rate (includes SD ≥ 6 months or objective response) was 53%, with a median progression-free survival (PFS) of 6.1 months (95% CI, 2.9-not estimable) and median overall survival (OS) of 9.7 months (95% CI, 6.7-not estimable). Three patients (~18%) achieved prolonged PFS and OS (PFS: 23.4+, 33.0, 59.7 months; OS: 23.4+, 43.6, 62.1+ months) in B-cell lymphoma unclassifiable, ovarian, and gastroesophageal cancers. Median dosages were 100% for ICIs and 50% for gene-targeted agents, with Grade 3-4 serious adverse events occurring in 24%. We additionally conducted a database search to evaluate the prevalence of biomarker-based dual therapy trials, which revealed only 1.3% (4/314) of such clinical trials included biomarkers for both targeted therapies and ICIs. These findings highlight the potential of dual biomarker-matched combination therapy even after multiple therapy lines and support further investigation of dual-matched therapy.