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SUMMARY
This exploratory biomarker analysis of the global, randomized phase 3 RATIONALE-305 trial evaluated the biomarkers and molecular subtypes associated with overall survival (OS) in patients with advanced gastric cancer or gastro-oesophageal junction adenocarcinoma receiving first-line tislelizumab plus chemotherapy (TIS + CT) versus placebo plus chemotherapy (PBO + CT). The evaluation utilized baseline tumor tissue and matched blood samples analyzed using RNA sequencing and whole exome sequencing. Results indicated that high levels of inflammation and low levels of immunosuppression gene expression signatures were associated with improved OS with TIS + CT versus PBO + CT. Additionally, high clonal tumor mutational burden, non–human leukocyte antigen B27 genotype, TP53 wildtype status, or the absence of 20q13.13 amplification were associated with improved OS in the TIS + CT group. In contrast, total tumor mutational burden did not demonstrate a clear association with OS.
ClinicalTrials.gov ID: NCT03777657
| Population | Intervention | Comparator | Outcome Measures |
|---|---|---|---|
| Patients with advanced gastric cancer or gastro-oesophageal junction adenocarcinoma enrolled in the global, randomized phase 3 RATIONALE-305 trial with baseline tumor tissue and matched blood samples available for biomarker analyses | Tislelizumab in combination with chemotherapy | Placebo in combination with chemotherapy | Biomarker and molecular subtypes associated with overall survival |
This exploratory analysis evaluated the biomarkers and molecular subtypes associated with overall survival in patients with advanced gastric cancer or gastro-oesophageal junction adenocarcinoma who were treated with first-line tislelizumab plus chemotherapy (TIS + CT) versus placebo plus chemotherapy (PBO + CT) in the global, randomized phase 3 RATIONALE-305 trial.
Gene expression signatures were assessed using RNA sequencing of baseline tumor tissue, with subgroups defined by median cutoff values. Whole exome sequencing of baseline tumor tissue and matched blood samples was used to evaluate tumor mutational burden, human leukocyte antigen genotypes, significantly mutated genes, and cytoband amplifications. Associations between biomarker status and overall survival were evaluated descriptively.
High levels of inflammation and low levels of immunosuppression gene expression signatures were associated with improved overall survival in patients treated with TIS + CT versus PBO + CT. High clonal tumor mutational burden was associated with improved overall survival, while total tumor mutational burden showed no clear association. Non–human leukocyte antigen B27 genotype, TP53 wildtype status, or absence of 20q13.13 amplification were also associated with improved overall survival in the TIS + CT group.
