Pharmacokinetics (PK) of Tiragolumab in First-in-Human Study in Patients with Mixed Solid Tumors (GO30103).
| Title: | Pharmacokinetics (PK) of Tiragolumab in First-in-Human Study in Patients with Mixed Solid Tumors (GO30103). |
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| Authors: | Garralda E; Early Drug Development Unit, Vall d'Hebron, Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.; Oh DY; Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul National University College of Medicine, Seoul, Republic of Korea.; Italiano A; Early Phase Trials Unit, Institut Bergonié, Bordeaux, and Faculty of Medicine, University of Bordeaux, Bordeaux, France.; Bedard PL; Princess Margaret Cancer Centre, University Health Network, Division of Medical Oncology & Hematology, University of Toronto, Toronto, Ontario, Canada.; Delord JP; Medical Oncology Department, IUCT Oncopole, Institut Claudius Regaud, Toulouse, France.; Calvo E; Centro Integral Oncológico Clara Campal, START Madrid - Clara Campal Comprehensive Cancer Center (CIOCC), Madrid, Spain.; LoRusso P; Yale Cancer Center, New Haven, CT, USA.; Wainberg Z; University of California Los Angeles, Los Angeles, CA, USA.; Cervantes A; Department of Medical Oncology, Hospital Clínico, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain.; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain.; Rodriguez-Vida A; Hospital del Mar-CIBERONC, IMIM Research Institute, Barcelona, Spain.; Shemesh CS; Department of Clinical Pharmacology, Genentech, Inc., South San Francisco, CA, USA.; Sane R; Department of Clinical Pharmacology, Genentech, Inc., South San Francisco, CA, USA.; Mendus D; Product Development Oncology, Genentech, Inc., South San Francisco, CA, USA.; Ding H; Department of Clinical Pharmacology, Genentech, Inc., South San Francisco, CA, USA.; Hendricks R; Department of BioAnalytical Sciences, Genentech, Inc., South San Francisco, CA, USA.; Meng R; Product Development Oncology, Genentech, Inc., South San Francisco, CA, USA.; Cho BC; Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.; Kim TW; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.; Wu B; Early Drug Development Unit, Vall d'Hebron, Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.; Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul National University College of Medicine, Seoul, Republic of Korea. |
| Source: | Journal of clinical pharmacology [J Clin Pharmacol] 2024 May; Vol. 64 (5), pp. 544-554. Date of Electronic Publication: 2024 Jan 17. |
| Publication Type: | Journal Article; Clinical Trial, Phase I; Research Support, Non-U.S. Gov't; Multicenter Study; Randomized Controlled Trial |
| Language: | English |
| Journal Info: | Publisher: Wiley Country of Publication: England NLM ID: 0366372 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-4604 (Electronic) Linking ISSN: 00912700 NLM ISO Abbreviation: J Clin Pharmacol Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2013- : Oxford : Wiley; Original Publication: Stamford, Conn., Hall Associates. |
| MeSH Terms: | Neoplasms*/drug therapy ; Antibodies, Monoclonal, Humanized*/pharmacokinetics ; Antibodies, Monoclonal, Humanized*/administration & dosage; Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Humans ; Male ; Female ; Middle Aged ; Adult ; Aged ; Dose-Response Relationship, Drug ; Infusions, Intravenous ; Area Under Curve |
| Abstract: | Tiragolumab is a first-in-class, fully human IgG1/kappa anti-TIGIT monoclonal antibody that blocks the binding of TIGIT to CD155 (the poliovirus receptor). We summarize the pharmacokinetics (PK) data from the phase 1a/1b GO30103 study of Q3W (every 3 weeks) sequential dosing of tiragolumab (2, 8, 30, 100, 400, 600, or 1200 mg) followed by atezolizumab (1200 mg), Q4W (every 4 weeks) sequential dosing (tiragolumab 840 mg followed by atezolizumab 1680 mg), and Q4W co-infusion (tiragolumab 840 mg plus atezolizumab 1680 mg). Serum samples were collected at multiple time points following tiragolumab and atezolizumab intravenous infusion in patients with solid tumors for PK and immunogenicity assessment. The serum PK profile of tiragolumab appeared to be biphasic, with a rapid distribution phase followed by a slower elimination phase when administered alone or in combination with atezolizumab. In phase 1a, across doses of tiragolumab ranging from 2 to 1200 mg (cycle 1), the geometric mean (GM), coefficient of variation (CV%), serum tiragolumab Cmax ranged from 0.682 to 270 µg/mL (18.6% to 36.5%) and Cmin ranged from 0.0125 to 75.3 µg/mL (0.0% to 24.2%). The GM systemic exposure (area under the plasma drug concentration-time curve, AUC0-21) ranged from 310 to 2670 µg day/mL (20.5% to 27.0%); interindividual variability in AUC0-21 ranged from 20.5% to 43.9%. Tiragolumab exposure increased in an approximately dose-proportional manner when administered alone or with atezolizumab at doses ≥100 mg. Postbaseline, 4/207 patients (1.9%) were positive for treatment-emergent antidrug antibodies (ADA) against tiragolumab, each at a single time point. Tiragolumab combined with atezolizumab demonstrated desirable PK properties, with no drug-drug interactions or immunogenicity liability. There were no meaningful differences in tiragolumab or atezolizumab exposure between the Q4W co-infusion and sequential dosing cohorts. ClinicalTrials.gov: NCT02794571 (date of registration June 6, 2016).; (© 2024 American College of Clinical Pharmacology.) |
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| Contributed Indexing: | Keywords: PD‐L1; TIGIT; atezolizumab; phase 1a/1b; tiragolumab |
| Molecular Sequence: | ClinicalTrials.gov NCT02794571 |
| Substance Nomenclature: | 0 (Antibodies, Monoclonal, Humanized); 52CMI0WC3Y (atezolizumab) |
| Entry Date(s): | Date Created: 20231218 Date Completed: 20240424 Latest Revision: 20250730 |
| Update Code: | 20260130 |
| DOI: | 10.1002/jcph.2397 |
| PMID: | 38105505 |
| Database: | MEDLINE |
Journal Article; Clinical Trial, Phase I; Research Support, Non-U.S. Gov't; Multicenter Study; Randomized Controlled Trial