▎WuXiEdited by Kant Content Team

Genentech, a member of Roche, announced positive results from the Phase III SKYSCRAPER-08 trial investigating tiragolumab, an investigational anti-TIGIT antibody, in combination therapy for the first-line treatment of esophageal squamous cell carcinoma (ESCC), in an abstract presented at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium. Analysis evaluated by an Independent Review Facility (IRF) showed,The trial met both primary endpoints. Compared with the control group, the combination therapy of tiragolumab + PD-L1 inhibitor atezolizumab + chemotherapy significantly improved patients' progression-free survival (PFS) and overall survival (OS).

In the trial, a total of 461 Asian patients with unresectable locally advanced, recurrent, or metastatic ESCC were enrolled and randomly assigned to receive tiragolumab + atezolizumab + chemotherapy combination therapy (n=229) or placebo + chemotherapy (n=232). As of June 15, 2022,The median PFS assessed by IRF in the tiragolumab combination therapy group was 6.2 months, significantly higher than 5.4 months in the control group (HR: 0.56, 95% CI: 0.45-0.70, P<0.0001).As of February 13, 2023,The median OS in the tiragolumab combination therapy group was 15.7 months, compared to 11.1 months in the control group (HR: 0.70, 95% CI: 0.55-0.88, P=0.0024).A generally consistent benefit of the combination therapy was observed across all subgroups. For a detailed summary of the efficacy assessment, please see the table below:

▲Summary of Key Efficacy Results from the SKYSCRAPER-08 Phase 3 Clinical Trial (Source: Reference [1])

The safety profile of the combination therapy is consistent with the known risks of the individual drugs.Among the two groups of patients, 98.2% experienced treatment-related adverse events (TRAE).Among them, 59.6% of patients in the tiragolumab combination therapy group and 56.4% of patients in the control group experienced grade 3/4 TRAE.Additionally, 2.6% of patients in the tiragolumab combination therapy group and 0.9% of patients in the control group experienced Grade 5 TRAE.

Tiragolumab is a novel immune checkpoint inhibitor, a monoclonal antibody targeting TIGIT with a complete Fc region.TIGIT is a novel inhibitory immune checkpoint, primarily expressed on the surface of T cells and natural killer (NK) cells, which can suppress the body's immune response to cancer.The TIGIT pathway complements the PD-L1/PD-1 pathway, so dual blockade with tiragolumab and atezolizumab may help overcome immune suppression and restore immune response.Evaluate Pharma's analysis report on the 2024 biopharmaceutical industry trends indicates that tiragolumab is one of the potential blockbuster pipelines in development.

Reference Reading:10 Potential Blockbuster R&D Pipelines in 2024!

NotableIt is reported by the industry media Fierce Biotech that currently in the late stageESCCThe standard first-line treatment for patients isPD-L1/PD-1Checkpoint Inhibitors Plus Platinum-Based DoubletChemotherapy.InSKYSCRAPER-08In the trial, the treatment regimen received by the control group did not includePD-L1/PD-1Checkpoint inhibitors, therefore, it is difficult to draw conclusions based on the trial results.tiragolumabWhether it can bring additional benefits to patients.Nevertheless, the trial results show that patients can benefit from the combination therapy regardless of the level of PD-L1 expression in the tumor.

And in response to this limitation,Roche is conducting another trial, SKYSCRAPER-07, the results of which will help further clarify whether tiragolumab treatment is beneficial.ESCCPatient.This Phase 3 trial is evaluating the efficacy and safety of tiragolumab and atezolizumab in treating patients with ESCC who have not experienced disease progression after concurrent chemoradiotherapy. One-third of the patients will receive both drugs, another third will receive a placebo plus atezolizumab, and the final third will receive two placebos. The trial will continue until 2027.

▲Tiragolumab First-Line Treatment Results for NSCLC and Hepatocellular Carcinoma (Image Source:Roche Official Website）

Also working in the TIGIT field are Gilead Sciences and Arcus Biosciences. In November last year, the two companies jointly announced the A1 cohort of the Phase 2 EDGE-Gastric clinical study.Preliminary ResultsAnalysis shows that the TIGIT-targeted antibody domvanalimab, combined with the PD-1-targeted antibody zimberelimab and chemotherapy, demonstrates a positive overall response rate in patients with locally advanced unresectable or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma. This effect is not influenced by the PD-L1 expression level of the patient's tumor. Data indicates,Treatment regimens including domvanalimab showed an overall response rate of 80% in patients with PD-L1 high-expression tumors (Tumor Activity Positive [TAP] ≥5%), compared to 46% in patients with PD-L1 low-expression tumors (TAP <5%) and 59% in the overall patient population., two of whom achieved complete remission.

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