Genentech’s Novel Anti-TIGIT Tiragolumab Granted FDA Breakthrough Therapy Designation in Combination With Tecentriq for PD-L1-High Non-Small Cell Lung Cancer


non-small cell lung cancer (NSCLC)


South San Francisco, CA -- January 4, 2021 -- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that tiragolumab, a novel cancer immunotherapy designed to bind to TIGIT, has been granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA), in combination with Tecentriq ® (atezolizumab) for the first-line treatment of people 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 the first anti-TIGIT molecule to be granted BTD from the FDA, and the designation is based on randomized data from the Phase II CITYSCAPE trial. CITYSCAPE provides the first evidence that targeting both immune inhibitory receptors, TIGIT and PD-L1, may enhance anti-tumor activity by potentially amplifying the immune response.

“We have been researching TIGIT as a novel cancer immunotherapy target for almost 10 years and we are pleased that the FDA has acknowledged the potential of tiragolumab to substantially improve outcomes for people with certain types of lung cancer,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “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.”

BTD is designed to accelerate the development and review of medicines intended to treat serious or life-threatening conditions, with preliminary evidence that indicates they may demonstrate a substantial improvement over existing therapies. This marks the 37th BTD for Genentech’s portfolio of medicines.

Tiragolumab in combination with Tecentriq has so far shown encouraging efficacy and safety in PD-L1-positive metastatic NSCLC based on data from the Phase II CITYSCAPE trial, the first randomized study in the anti-TIGIT field. Full results from CITYSCAPE, presented at the American Society of Clinical Oncology 2020 Virtual Scientific Program, showed that at an average of 10.9 months follow-up, the combination showed an improvement in the overall response rate (ORR; 37% vs. 21% with Tecentriq alone) and a 42% reduction in the risk of disease worsening or death (progression-free survival; PFS) compared with Tecentriq alone. An exploratory analysis in people with high levels of PD-L1 (tumor proportion score; TPS ≥ 50%) showed a clinically meaningful ORR vs. Tecentriq alone (66% vs. 24%) and median PFS was not reached (vs. 4.11 months with Tecentriq alone; HR=0.30, 95% CI: 0.15–0.61). The data suggest that tiragolumab plus Tecentriq was generally well-tolerated, showing similar rates of all Grade 3 or more all-cause adverse events when combining the two immunotherapies compared with Tecentriq alone (48% vs. 44%).

Genentech is investigating the potential of tiragolumab in a broad development program that builds on the benefit observed with Tecentriq while expanding into earlier stages of disease and new areas of unmet need. This includes randomized trials in metastatic NSCLC (SKYSCRAPER-01 and SKYSCRAPER-06) and small cell lung cancer (SKYSCRAPER-02), as well as exploration of tiragolumab in earlier stages, including stage III NSCLC (SKYSCRAPER-03) and locally advanced esophageal cancer (SKYSCRAPER-07). Tiragolumab is also being investigated in metastatic esophageal squamous cancer (SKYSCRAPER-08) and cervical cancer (SKYSCRAPER-04), with early trials in other tumor types.

Biomarker analyses from the CITYSCAPE study will be presented at the IASLC 2020 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer, taking place from January 28-31, 2021 (Efficacy of Tiragolumab + Atezolizumab in PD-L1 IHC and TIGIT Subgroups in the Phase II CITYSCAPE Study in First-Line NSCLC).

Dual blockade of the TIGIT and PD-L1 pathways

TIGIT and PD-L1 are proteins that play a role in suppression of the immune system. Blocking both pathways simultaneously with tiragolumab and Tecentriq has the potential to increase anti-tumor activity by enhancing the body’s immune response to cancer cells. Targeting multiple immune pathways in this way has the potential to build upon previous advances in cancer immunotherapy, expand into earlier stages of disease and provide new treatment options in areas of high unmet need.

About the CITYSCAPE study

CITYSCAPE is a global Phase II, randomized and blinded study evaluating tiragolumab plus Tecentriq® (atezolizumab) compared with Tecentriq alone in 135 patients with first-line PD-L1-positive, locally advanced unresectable or metastatic non-small cell lung cancer. Patients were randomized 1:1 to receive either tiragolumab plus Tecentriq or placebo plus Tecentriq, until progressive disease or loss of clinical benefit. Co-primary endpoints are overall response rate and progression-free survival. Secondary endpoints include safety and overall survival.

About tiragolumab

Tiragolumab is a monoclonal antibody designed to bind with TIGIT, a protein receptor on immune cells. Tiragolumab works as an immune amplifier, by potentially enhancing the body’s immune response. By binding to TIGIT, tiragolumab blocks its interaction with a protein called poliovirus receptor (PVR, or CD155) that can suppress the body’s immune response. Blockade of TIGIT and PD-L1 may synergistically enable the re-activation of T cells and enhance NK cell anti-tumor activity. 

About Genentech in cancer immunotherapy

Genentech has been developing medicines to redefine treatment in oncology for more than 35 years, and today, realizing the full potential of cancer immunotherapy is a major area of focus. With more than 20 immunotherapy molecules in development, Genentech is investigating the potential benefits of immunotherapy alone, and in combination with various chemotherapies, targeted therapies and other immunotherapies with the goal of providing each person with a treatment tailored to harness their own unique immune system.

In addition to Genentech’s approved PD-L1 checkpoint inhibitor, the company’s broad cancer immunotherapy pipeline includes other checkpoint inhibitors, individualized neoantigen therapies and T cell bispecific antibodies. For more information visit

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit

Source: Genentech

Posted: January 2021

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