The Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to tiragolumab (Genentech), in combination with atezolizumab (Tecentriq®; Genentech), for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression with no EGFR or ALK genomic tumor aberrations.

Tiragolumab is a monoclonal antibody that works by binding to TIGIT, a protein receptor on immune cells, and blocking its interaction with the poliovirus receptor. The Company believes that combining tiragolumab with atezolizumab, a PD-L1 blocking antibody, will increase anti-tumor activity by enhancing the body’s immune response to cancer cells. 

The designation is supported by data from the phase 2 CITYSCAPE study that assessed the efficacy and safety of tiragolumab plus atezolizumab in 135 chemotherapy-naive adults with locally advanced unresectable or metastatic PD-L1-selected NSCLC. Patients were randomized 1:1 to receive either tiragolumab plus atezolizumab or atezolizumab alone. The co-primary end points were overall response rate (ORR) and progression-free survival (PFS).

Results showed a greater improvement in ORR with tiragolumab plus atezolizumab vs atezolizumab alone (37% vs 21%, respectively), at an average of 10.9 months follow-up. The combination therapy was also associated with a 42% reduction in the risk of disease worsening or death compared with atezolizumab alone. 

Additionally, among patients with high levels of PD-L1 (tumor proportion score [TPS] greater than or equal to 50%), 66% of patients in the tiragolumab plus atezolizumab arm achieved a clinically meaningful ORR vs 24% in the atezolizumab arm. The median PFS was not reached in the tiragolumab plus atezolizumab arm and was 4.11 months in the atezolizumab arm (hazard ratio 0.30; 95% CI, 0.15-0.61).

The Company is also investigating the combination of tiragolumab and atezolizumab for the treatment of metastatic NSCLC (SKYSCRAPER-01 and SKYSCRAPER-06), small cell lung cancer (SKYSCRAPER-02), stage III NSCLC (SKYSCRAPER-03), and locally advanced esophageal cancer (SKYSCRAPER-07). Tiragolumab is also being evaluated for the treatment of metastatic esophageal squamous cancer (SKYSCRAPER-08) and cervical cancer (SKYSCRAPER-04).

“We look forward to advancing our tiragolumab development program, which includes chemotherapy-free combinations and trials in early stages of disease across multiple cancer types with high unmet need,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development.

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Genentech’s novel Anti-TIGIT tiragolumab granted FDA Breakthrough Therapy designation in combination with Tecentriq for PD-L1-high non-small cell lung cancer. [press release]. South San Francisco, CA: Genentech; January 5, 2021.