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Tiragolumab (anti-TIGIT)

(RG6058, MTIG7192A) 

Breast

Phase I

A Study of the Safety, Efficacy, and Pharmacokinetics of Tiragolumab in Combination With Atezolizumab and Chemotherapy in Participants With Triple-Negative Breast Cancer

NCT04584112

Head and Neck

Phase II

A Study of Atezolizumab Plus Tiragolumab and Atezolizumab Plus Placebo as First-Line Treatment in Participants With Recurrent/Metastatic PD-L1 Positive Squamous Cell Carcinoma of the Head and Neck (SKYSCRAPER-09)

NCT04665843

Gastrointestinal

Phase III

A Study of Atezolizumab With or Without Tiragolumab in Participants With Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma

NCT04543617

A Study of Atezolizumab Plus Tiragolumab in Combination With Paclitaxel and Cisplatin Compared With Paclitaxel and Cisplatin as First-Line Treatment in Participants With Unresectable Locally Advanced, Unresectable Recurrent, or Metastatic Esophageal Carcinoma

NCT04540211

Gynecologic

Phase II

A Study of Tiragolumab Plus Atezolizumab and Atezolizumab Monotherapy in Participants With Metastatic and/or Recurrent PD-L1−Positive Cervical Cancer (SKYSCRAPER-04)

NCT04300647

Hematology

Phase I

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Pharmacodynamics (PD), and Preliminary Activity of Tiragolumab in Participants With Relapsed or Refractory Multiple Myeloma or With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

NCT04045028

Lung

Phase III

A Study of Tiragolumab in Combination With Atezolizumab Compared With Placebo in Combination With Atezolizumab in Patients With Previously Untreated Locally Advanced Unresectable or Metastatic PD-L1-Selected Non-Small Cell Lung Cancer (SKYSCRAPER-01)

NCT04294810

A Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Patients With Untreated Extensive-Stage Small Cell Lung Cancer (SKYSCRAPER-02)

NCT04256421

A study of Atezolizumab and Tiragolumab Compared with Durvalumab in Participants with Locally Advanced, Unresectable Stage III Non-Small Cell Lung Cancer (NSCLC)

NCT04513925

Phase II

A Study Evaluating the Safety and Efficacy of Neoadjuvant and Adjuvant Tiragolumab Plus Atezolizumab, With or Without Platinum-Based Chemotherapy, in Participants With Previously Untreated Locally Advanced Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer (SKYSCRAPER-05) 

NCT04832854

A Study of Tiragolumab in Combination With Atezolizumab Plus Pemetrexed and Carboplatin/Cisplatin Versus Pembrolizumab Plus Pemetrexed and Carboplatin/Cisplatin in Participants With Previously Untreated Advanced Non-Squamous Non-Small Cell Lung Cancer (SKYSCRAPER-06)

NCT04619797

Solid Tumor

Phase I

Safety and Pharmacokinetics (PK) of Escalating Doses of MTIG7192A as a Single Agent and in Combination With Atezolizumab With and Without Chemotherapy in Locally Advanced or Metastatic Tumors

NCT02794571

This compound and its use are investigational and have not been approved by the US Food and Drug Administration. Efficacy and safety have not been established. The information presented should not be construed as a recommendation for use. The relevance of findings in preclinical studies to humans is currently being evaluated.

Targeting TIGIT: A novel immune checkpoint

Tiragolumab, an investigational molecule

TIGIT (T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains) is a novel negative immune checkpoint, expressed on T cells and NK cells.1,2

TIGIT receptor on T cells and NK cells

TIGIT is a coinhibitory receptor that binds to PVR on APCs and tumor cells in various solid and hematologic tumors.1-3 TIGIT dampens the immune response by competing with its costimulatory counterpart, CD226, for binding to PVR.1,2 Once bound to TIGIT, tiragolumab may restore anti-tumor immunity, thereby complementing PD-L1 inhibition, as shown in preclinical models.1 TIGIT was identified at Genentech.2,4

Tiragolumab is an investigational, fully human monoclonal IgG1 antibody designed to prevent PVR-TIGIT interaction.3

Tiragolumab is designed to prevent PVR-TIGIT interaction

Preclinical studies suggest that targeting both TIGIT and PD-L1 may synergistically enhance immune-mediated tumor rejection.1,5,6

Targeting TIGIT on effector T cell

Targeting TIGIT may enhance Teff  function.1

Targeting TIGIT on NK cell

Targeting TIGIT may activate NK cells.5

Targeting TIGIT on regulatory T cell

Targeting TIGIT may counter T reg-mediated immune suppression.6

APC=antigen-presenting cell; IgG1=immunoglobulin G1; NK=natural killer; PD-1=programmed cell death protein 1; PD-L1=programmed cell-death ligand 1; PVR=poliovirus receptor; Teff=effector T cell; Treg=regulatory T cell; TIGIT=T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains.

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