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Tiragolumab

Agent Description

Tiragolumab is a fully human IgG1 monoclonal antibody that binds T-cell immunoreceptors with Ig and ITIM domains (TIGIT). TIGIT is an immune inhibitory receptor that is expressed on the surface of activated T-cell and natural killer (NK)-cell subsets. It interacts with high affinity with CD155 (also known as poliovirus receptor [PVR]).

Mechanism of Action

Tiragolumab targets T-cell immunoreceptor on activated T-cell and natural killer (NK) cell subsets and prevents interaction with CD155 (poliovirus receptor [PVR]) to limit cellular proliferation, effector cytokine production, and killing of target tumor cells.

Classification

Fully human immunoglobulin monoclonal antibody that is produced in Chinese hamster ovary cells.

Molecular Target

T cells and natural killer (NK) cell subsets

Monograph

Therapeutic blockade of TIGIT by tiragolumab represents an attractive strategy for cancer therapy. It is expected to enhance the magnitude and quality of tumor-specific T-cell responses. This may result in improved meaningful anti-tumor activity when tiragolumab is combined with other CIT and chemotherapy. The available nonclinical and clinical data provide a strong rationale for evaluating the potential clinical benefit of tiragolumab in patients with cancer.

Studies of Interest

Tiragolumab is currently being studied at 600 mg Q3W in NSCLC, cervical, and esophageal cancers and at 420 mg every 2 weeks (Q2W) or 840 Q4W in TNBC and NSCLC, respectively.

Studies of interest include:

  • Phase I signal-seeking trials aimed to explore the underlying mechanism and potential synergy of these novel immunotherapy combinations with tiragolumab (e.g., phase I study of tiragolumab + anti-CD47 in solid tumors)
  • Phase I signal-seeking trials aimed at exploring tyrosine kinase inhibitors (TKIs), where TKIs are established standard of care. Trials aimed at exploring the underlying mechanism and potential synergy of novel combinations with tiragolumab (e.g., tiragolumab+/- CIT + TKI in RCC)
  • Phase I signal-seeking trials aimed at exploring radiation therapy either given prior to the administration of tiragolumab +/- other CIT, chemotherapy agents or administered in combination with tiragolumab +/- other CITs, chemotherapy in early disease (e.g., RT +/- tiragolumab +/- CIT; chemotherapy in the neoadjuvant setting)
  • Combination of tiragolumab + PARPi +/- checkpoint inhibitors in HRD-driven tumors (e.g., gynecologic or prostate cancers)

Information collaborator would like included in investigator proposals

Sponsor-investigator must indicate appropriate facilities/personnel, experience treating patients in desired research population and that they have an adequate sample size they can enroll into study, and a proven track record for conducting and publishing research. Formulary LOI proposal needs to describe if they have ongoing studies at their institution that would compete with the research population of interest during the expected patient accrual window.

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