Roche’s Anti-TIGIT Tiragolumab Granted FDA Breakthrough Therapy Designation in Combination with Tecentriq for PD-L1-High NSCLC

January 07, 2021 /BioValleyBIOON/ -- Roche recently announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to tiragolumab, a novel cancer immunotherapy targeting TIGIT, in combination with the anti-PD-L1 therapy Tecentriq (atezolizumab), for the first-line treatment of tumors with high PD-L1 expression and without EGFR or ALK genomicTumorPatients with metastatic non-small cell lung cancer (NSCLC) harboring rearrangements.

It is particularly worth mentioning that,Tiragolumab is the first to receive U.S.FDAThe anti-TIGIT molecule granted BTD also marks the 37th BTD received by Roche’s pharmaceutical products.This BTD is based on randomized data from the Phase II CITYSCAPE study, which provided the first evidence confirming that simultaneous targeting of the immunosuppressive receptors TIGIT and PD-L1 may enhance anti-TumorActivity.

Tiragolumab is a novel cancer immunotherapy targeting TIGIT, an immune checkpoint protein expressed on immune cells that was identified by Roche’s own scientists. Tiragolumab acts as an immune amplifier by potentially enhancing the body’s immune response. Both TIGIT and PD-L1 play important roles in immune suppression, and simultaneous blockade of these two pathways may enhance anti-Tumoractivity. By targeting multiple immune pathways in this manner, there is potential to build on previous advances in cancer immunotherapy, expand into earlier stages of disease, and provide new therapeutic options in areas with high unmet medical needs.

Levi Garraway, M.D., Ph.D., Chief Medical Officer and Global Head of Product Development at Roche, stated: “For nearly a decade, we have been investigating TIGIT as a novel target for cancer immunotherapy, and we are pleasedFDA“The potential of tiragolumab to significantly improve outcomes in patients with certain types of lung cancer has been recognized. We look forward to advancing our tiragolumab development program, which includes chemotherapy-free combination therapies and early-stage trials across multiple cancer types with high unmet needs.”

CITYSCAPE is the first randomized study in the TIGIT field. This global, randomized, double-blind study evaluated the efficacy and safety of tiragolumab in combination with Tecentriq versus Tecentriq monotherapy as initial (first-line) treatment in 135 patients with PD-L1-positive, locally advanced unresectable or metastatic non-small cell lung cancer (NSCLC). The co-primary endpoints were objective response rate (ORR) and progression-free survival (PFS), and secondary endpoints included safety and overall survival (OS).

The results showed that tiragolumab in combination with Tecentriq as first-line treatment for PD-L1-positive metastatic NSCLC demonstrated encouraging efficacy and safety. The full results of this study have been presented at the American Society of Clinical Oncology (ASCO)TumorAmerican Society of Clinical Oncology (ASCO) 2020 Virtual ScientificMeetingPublished above.

The specific data are as follows: (1) With a median follow-up of 10.9 months, in the intent-to-treat (ITT) patient population, the combination therapy of tiragolumab plus Tecentriq met both primary endpoints compared with Tecentriq monotherapy: a significantly higher objective response rate (ORR) (37% vs. 21%) and a significant 42% reduction in the risk of disease progression or death (median PFS: 5.6 months vs. 3.9 months; HR=0.58). (2) ForPatients with High PD-L1 Expression (TPS ≥50%)An exploratory analysis conducted showed that, compared with Tecentriq monotherapy,Tiragolumab plus Tecentriq combination therapy significantly improved the ORR (66% vs. 24%) and significantly reduced the risk of disease progression or death by 70% (median PFS: not reached vs. 4.11 months; HR=0.30, 95% CI: 0.15–0.61).(3) In this study, the combination of tiragolumab and Tecentriq was well tolerated, with a similar incidence of all-cause grade 3 or higher adverse events (AEs) compared to Tecentriq monotherapy (48% vs. 44%).

From the CITYSCAPE StudyBiomarkersThe analysis will be presented at the IASLC 2020 World Conference on Lung Cancer, hosted by the International Association for the Study of Lung Cancer, from January 28 to 31, 2021.

Tiragolumab is a monoclonal antibody that targets and binds to TIGIT, a protein receptor expressed on immune cells. By binding to TIGIT, tiragolumab blocks the interaction between TIGIT and a protein known as poliovirus receptor (PVR, or CD155). The binding of TIGIT to PVR inhibits the body’s immune response.

Tecentriq belongs to anti-PD-(L)1 therapies; this drug is a monoclonal antibody that targets and binds to tumor cells andTumorTecentriq blocks the interaction of PD-L1, a protein expressed on infiltrating immune cells, with its receptors PD-1 and B7.1. By inhibiting PD-L1, Tecentriq activates T cells and has the potential to serve as a foundational combination therapy for cancer immunotherapy, targeted agents, and various chemotherapy regimens.

Blocking TIGIT and PD-L1 may synergistically activate T cells and enhance the anti-Tumoractivity. This is the scientific basis for the combination study of tiragolumab with Tecentriq.

Currently, Roche is evaluating the potential of tiragolumab in a broad development program built on the clinical benefits observed with the combination of tiragolumab and Tecentriq, while expanding into earlier stages of disease and new indications with significant unmet medical needs. The program includes randomized trials in metastatic non-small cell lung cancer (NSCLC) (SKYSCRAPER-01 and SKYSCRAPER-06 studies) and small cell lung cancer (SKYSCRAPER-02 study), as well as exploration of tiragolumab in earlier-stage settings, including stage III NSCLC (SKYSCRAPER-07 study) and locally advanced esophageal cancer (SKYSCRAPER-07 study). Furthermore, tiragolumab is being investigated in metastatic esophageal squamous cell carcinoma (SKYSCRAPER-08 study) and cervical cancer (SKYSCRAPER-04 study), with multiple early-phase trials assessing tiragolumab for other typesTumor(Bioon.com)

Original Source: Roche’s novel anti-TIGIT tiragolumab grantedFDA Breakthrough Therapy Designation in combination with Tecentriq for PD-L1-high non-small cell lung cancer