Safety and Pharmacokinetics (PK) of Escalating Doses of Tiragolumab as a Single Agent and in Combination With Atezolizumab and/or Other Anti-Cancer Therapies in Locally Advanced or Metastatic Tumors

This first-in-human open-label, multicenter, dose-escalation and expansion study is designed to evaluate the safety, tolerability, and PK of tiragolumab alone or in combination with atezolizumab and/or other anti-cancer therapies in participants with locally advanced, recurrent, or metastatic incurable tumors for whom standard therapy does not exist, has proven to be ineffective or intolerable, or is considered inappropriate, or for whom a clinical trial of an investigational agent is a recognized standard of care.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Adults 18 years of age or older
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy at least 12 weeks
* Adequate hematologic and end organ function
* Histologic documentation of locally advanced, recurrent, or metastatic incurable malignancy that has progressed after at least one available standard therapy; or for which standard therapy has proven ineffective, intolerable, or considered inappropriate; or for which a clinical trial of an investigational agent is a recognized standard of care
* Confirmed availability of representative tumor specimens
* Measurable disease according to RECIST Version 1.1

Exclusion Criteria:

* Any anti-cancer therapy, whether investigational or approved, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment
* Malignancies other than disease under study within 5 years prior to Day 1 of Cycle 1
* Primary central nervous system (CNS) malignancy, or untreated/active CNS metastases
* Leptomeningeal disease
* History of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or evidence of active pneumonitis on Screening chest computed tomograph (CT) scan
* History of autoimmune disease
* Positive human immunodeficiency virus (HIV) test
* Active hepatitis B or C, or tuberculosis
* Severe infection within 4 weeks prior to randomization
* Prior allogeneic bone marrow or solid organ transplant
* Significant cardiovascular disease
* Known clinically significant liver disease

• DERIVEDShemesh CS, Wang Y, An A, Ding H, Chan P, Liu Q, Chen YW, Wu B, Wu Q, Wang X. Phase I pharmacokinetic, safety, and preliminary efficacy study of tiragolumab in combination with atezolizumab in Chinese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2024 Jul;94(1):45-55. doi: 10.1007/s00280-024-04650-y. Epub 2024 Mar 7. PMID 38451273
• DERIVEDGarralda E, Oh DY, Italiano A, Bedard PL, Delord JP, Calvo E, LoRusso P, Wainberg Z, Cervantes A, Rodriguez-Vida A, Shemesh CS, Sane R, Mendus D, Ding H, Hendricks R, Meng R, Cho BC, Kim TW, Wu B. Pharmacokinetics (PK) of Tiragolumab in First-in-Human Study in Patients with Mixed Solid Tumors (GO30103). J Clin Pharmacol. 2024 May;64(5):544-554. doi: 10.1002/jcph.2397. Epub 2024 Jan 17. PMID 38105505
• DERIVEDKim TW, Bedard PL, LoRusso P, Gordon MS, Bendell J, Oh DY, Ahn MJ, Garralda E, D'Angelo SP, Desai J, Hodi FS, Wainberg Z, Delord JP, Cassier PA, Cervantes A, Gil-Martin M, Wu B, Patil NS, Jin Y, Hoang T, Mendus D, Wen X, Meng R, Cho BC. Anti-TIGIT Antibody Tiragolumab Alone or With Atezolizumab in Patients With Advanced Solid Tumors: A Phase 1a/1b Nonrandomized Controlled Trial. JAMA Oncol. 2023 Nov 1;9(11):1574-1582. doi: 10.1001/jamaoncol.2023.3867. PMID 37768658