Pharmacokinetics (PK) of tiragolumab in first-in-human study in patients with mixed solid tumors (GO30103)

Garralda, Elena; Oh, Do Youn; Italiano, Antoine; Bedard, Philippe L.; Delord, Jean-Pierre; Calvo, Emiliano; LoRusso, Patricia; Wainberg, Zev A.; Cervantes, Andrés; Rodriguez-Vida, Alejo; Shemesh, Colby S.; Sane, Rucha; Mendus, Diana; Ding, Hao; Hendricks, Robert; Meng, Ray; Cho, Byoung Chul; Kim, Tae Won; Wu, Benjamin

Pharmacokinetics (PK) of tiragolumab in first-in-human study in patients with mixed solid tumors (GO30103)

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dc.contributor.author Garralda, Elena
dc.contributor.author Oh, Do Youn
dc.contributor.author Italiano, Antoine
dc.contributor.author Bedard, Philippe L.
dc.contributor.author Delord, Jean-Pierre
dc.contributor.author Calvo, Emiliano
dc.contributor.author LoRusso, Patricia
dc.contributor.author Wainberg, Zev A.
dc.contributor.author Cervantes, Andrés
dc.contributor.author Rodriguez-Vida, Alejo
dc.contributor.author Shemesh, Colby S.
dc.contributor.author Sane, Rucha
dc.contributor.author Mendus, Diana
dc.contributor.author Ding, Hao
dc.contributor.author Hendricks, Robert
dc.contributor.author Meng, Ray
dc.contributor.author Cho, Byoung Chul
dc.contributor.author Kim, Tae Won
dc.contributor.author Wu, Benjamin
dc.date.accessioned 2024-10-24T06:55:24Z
dc.date.available 2024-10-24T06:55:24Z
dc.date.issued 2024
dc.description.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).
dc.format.mimetype application/pdf
dc.identifier.citation Garralda E, Oh DY, Italiano A, Bedard PL, Delord JP, Calvo E, et al. Pharmacokinetics (PK) of tiragolumab in first-in-human study in patients with mixed solid tumors (GO30103). J Clin Pharmacol. 2024 May;64(5):544-54. DOI: 10.1002/jcph.2397
dc.identifier.doi http://dx.doi.org/10.1002/jcph.2397
dc.identifier.issn 0091-2700
dc.identifier.uri http://hdl.handle.net/10230/68333
dc.language.iso eng
dc.publisher Wiley
dc.relation.ispartof J Clin Pharmacol. 2024 May;64(5):544-54
dc.rights © 2024 American College of Clinical Pharmacology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.keyword PD‐L1
dc.subject.keyword TIGIT
dc.subject.keyword Atezolizumab
dc.subject.keyword Phase 1a/1b
dc.subject.keyword Tiragolumab
dc.title Pharmacokinetics (PK) of tiragolumab in first-in-human study in patients with mixed solid tumors (GO30103)
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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