2. Academic Validation
  3. Model Informed Dosing Regimen and Phase I Results of the Anti-PD-1 Antibody Budigalimab (ABBV-181)

Model Informed Dosing Regimen and Phase I Results of the Anti-PD-1 Antibody Budigalimab (ABBV-181)

  • Clin Transl Sci. 2021 Jan;14(1):277-287. doi: 10.1111/cts.12855.
John Powderly 1,  Alexander Spira 2 3,  Shunsuke Kondo 4,  Toshihiko Doi 5,  Jason J Luke 6,  Drew Rasco 7,  Bo Gao 8,  Minna Tanner 9,  Philippe A Cassier 10,  Anas Gazzah 11,  Antoine Italiano 12,  Diego Tosi 13,  Daniel E Afar 14,  Apurvasena Parikh 15,  Benjamin Engelhardt 16,  Stefan Englert 17,  Stacie L Lambert 14,  Sreeneeranj Kasichayanula 15,  Sven Mensing 16,  Rajeev Menon 18,  Gregory Vosganian 14,  Anthony Tolcher 19
Affiliations

Affiliations

  • 1 Carolina BioOncology Institute, Huntersville, North Carolina, USA.
  • 2 Virginia Cancer Specialists, Fairfax, Virginia, USA.
  • 3 Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
  • 4 Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan.
  • 5 Department of Experimental Therapeutics, National Cancer Center Hospital East, Kashiwa, Japan.
  • 6 Division of Hematology/Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.
  • 7 START Center for Cancer Care, San Antonio, Texas, USA.
  • 8 Blacktown Cancer and Haematology Centre, Blacktown, Australia.
  • 9 Department of Oncology, Tampere University Hospital, Tampere, Finland.
  • 10 Department of Medical Oncology, Centre Léon Bérard, Lyon, France.
  • 11 Drug Development Department, Gustave Roussy Université Paris-Saclay, Villejuif, France.
  • 12 Department of Medical Oncology, Institut Bergonié, Bordeaux, France.
  • 13 Department of Medical Oncology, Institut Régional du Cancer de Montpellier, Montpellier, France.
  • 14 Oncology Early Development, AbbVie, Inc., Redwood City, California, USA.
  • 15 Clinical Pharmacology and Pharmacometrics, AbbVie, Inc., Redwood City, California, USA.
  • 16 Clinical Pharmacology and Pharmacometrics, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen am Rhein, Germany.
  • 17 Data and Statistical Sciences, AbbVie Deutschland GmbH & Co KG, Ludwigshafen, Germany.
  • 18 Clinical Pharmacology and Pharmacometrics, AbbVie Inc., North Chicago, Illinois, USA.
  • 19 Next Oncology, San Antonio, Texas, USA.
PMID: 32770720 DOI: 10.1111/cts.12855
Abstract

Budigalimab is a humanized, recombinant, Fc mutated IgG1 monoclonal antibody targeting programmed cell death 1 (PD-1) receptor, currently in phase I clinical trials. The safety, efficacy, pharmacokinetics (PKs), pharmacodynamics (PDs), and budigalimab dose selection from monotherapy dose escalation and multihistology expansion cohorts were evaluated in patients with previously treated advanced solid tumors who received budigalimab at 1, 3, or 10 mg/kg intravenously every 2 weeks (Q2W) in dose escalation, including Japanese patients that received 3 and 10 mg/kg Q2W. PK modeling and PK/PD assessments informed the dosing regimen in expansion phase using data from body-weight-based dosing in the escalation phase, based on which patients in the multihistology expansion cohort received flat doses of 250 mg Q2W or 500 mg every four weeks (Q4W). Immune-related adverse events (AEs) were reported in 11 of 59 patients (18.6%), of which 1 of 59 (1.7%) was considered grade ≥ 3 and the safety profile of budigalimab was consistent with other PD-1 targeting agents. No treatment-related grade 5 AEs were reported. Four responses per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 were reported in the dose escalation cohort and none in the multihistology expansion cohort. PK of budigalimab was approximately dose proportional and sustained > 99% peripheral PD-1 receptor saturation was observed by 2 hours postdosing, across doses. PK/PD and safety profiles were comparable between Japanese and Western patients, and exposure-safety analyses did not indicate any trends. Observed PK and PD-1 receptor saturation were consistent with model predictions for flat doses and less frequent regimens, validating the early application of PK modeling and PK/PD assessments to inform the recommended dose and regimen, following dose escalation.

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