Phase I Study of Safety and Pharmacokinetics of RO7297089, an Anti-BCMA/CD16a Bispecific Antibody, in Patients with Relapsed, Refractory Multiple Myeloma

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

Phase I Study of Safety and Pharmacokinetics of RO7297089, an Anti-BCMA/CD16a Bispecific Antibody, in Patients with Relapsed, Refractory Multiple Myeloma. / Plesner, Torben; Harrison, Simon J.; Quach, Hang; Lee, Cindy; Bryant, Adam; Vangsted, Annette; Estell, Jane; Delforge, Michel; Offner, Fritz; Twomey, Patrick; Choeurng, Voleak; Li, Junyi; Hendricks, Robert; Ruppert, Shannon M.; Sumiyoshi, Teiko; Miller, Karen; Cho, Eunpi; Schjesvold, Fredrik.

I: Clinical Hematology International, Bind 5, Nr. 1, 2023, s. 43-51.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Plesner, T, Harrison, SJ, Quach, H, Lee, C, Bryant, A, Vangsted, A, Estell, J, Delforge, M, Offner, F, Twomey, P, Choeurng, V, Li, J, Hendricks, R, Ruppert, SM, Sumiyoshi, T, Miller, K, Cho, E & Schjesvold, F 2023, 'Phase I Study of Safety and Pharmacokinetics of RO7297089, an Anti-BCMA/CD16a Bispecific Antibody, in Patients with Relapsed, Refractory Multiple Myeloma', Clinical Hematology International, bind 5, nr. 1, s. 43-51. https://doi.org/10.1007/s44228-022-00023-5

APA

Plesner, T., Harrison, S. J., Quach, H., Lee, C., Bryant, A., Vangsted, A., Estell, J., Delforge, M., Offner, F., Twomey, P., Choeurng, V., Li, J., Hendricks, R., Ruppert, S. M., Sumiyoshi, T., Miller, K., Cho, E., & Schjesvold, F. (2023). Phase I Study of Safety and Pharmacokinetics of RO7297089, an Anti-BCMA/CD16a Bispecific Antibody, in Patients with Relapsed, Refractory Multiple Myeloma. Clinical Hematology International, 5(1), 43-51. https://doi.org/10.1007/s44228-022-00023-5

Vancouver

Plesner T, Harrison SJ, Quach H, Lee C, Bryant A, Vangsted A o.a. Phase I Study of Safety and Pharmacokinetics of RO7297089, an Anti-BCMA/CD16a Bispecific Antibody, in Patients with Relapsed, Refractory Multiple Myeloma. Clinical Hematology International. 2023;5(1):43-51. https://doi.org/10.1007/s44228-022-00023-5

Author

Plesner, Torben ; Harrison, Simon J. ; Quach, Hang ; Lee, Cindy ; Bryant, Adam ; Vangsted, Annette ; Estell, Jane ; Delforge, Michel ; Offner, Fritz ; Twomey, Patrick ; Choeurng, Voleak ; Li, Junyi ; Hendricks, Robert ; Ruppert, Shannon M. ; Sumiyoshi, Teiko ; Miller, Karen ; Cho, Eunpi ; Schjesvold, Fredrik. / Phase I Study of Safety and Pharmacokinetics of RO7297089, an Anti-BCMA/CD16a Bispecific Antibody, in Patients with Relapsed, Refractory Multiple Myeloma. I: Clinical Hematology International. 2023 ; Bind 5, Nr. 1. s. 43-51.

Bibtex

@article{5725c4811fbd45f7bd549e98ded770ce,

title = "Phase I Study of Safety and Pharmacokinetics of RO7297089, an Anti-BCMA/CD16a Bispecific Antibody, in Patients with Relapsed, Refractory Multiple Myeloma",

abstract = "Introduction: This phase 1 trial assessed the safety, pharmacokinetics, and preliminary antitumor activity of RO7297089, an anti-BCMA/CD16a bispecific antibody. Methods: RO7297089 was administered weekly by intravenous infusion to patients with relapsed/refractory multiple myeloma. The starting dose was 60 mg in this dose-escalation study utilizing a modified continual reassessment method with overdose control model. Results: Overall, 27 patients were treated at doses between 60 and 1850 mg. The maximally administered dose was 1850 mg due to excipients in the formulation that did not allow for higher doses to be used. The maximum tolerated dose was not reached. The most common adverse events irrespective of grade and relationship to the drug were anemia, infusion-related reaction, and thrombocytopenia. Most common treatment-related grade ≥ 3 toxicities were ALT/AST increase and reduced lymphocyte count. Pharmacokinetic studies suggested non-linear pharmacokinetics and target-mediated drug disposition, with a trend of approaching linear pharmacokinetics at doses of 1080 mg and higher. Partial response was observed in two patients (7%), minimal response in two patients (7%), and stable disease in 14 patients (52%). Conclusions: RO7297089 was well tolerated at doses up to 1850 mg, and the efficacy data supported activity of RO7297089 in multiple myeloma. Combination with other agents may further enhance its potential as an innate immune cell engager in multiple myeloma. Trial Registration: ClinicalTrials.gov: NCT04434469; Registered June 16, 2020; https://www.clinicaltrials.gov/ct2/show/NCT04434469.",

keywords = "BCMA, CD16a, Clinical trial, Multiple myeloma, RO7297089",

author = "Torben Plesner and Harrison, {Simon J.} and Hang Quach and Cindy Lee and Adam Bryant and Annette Vangsted and Jane Estell and Michel Delforge and Fritz Offner and Patrick Twomey and Voleak Choeurng and Junyi Li and Robert Hendricks and Ruppert, {Shannon M.} and Teiko Sumiyoshi and Karen Miller and Eunpi Cho and Fredrik Schjesvold",

note = "Publisher Copyright: {\textcopyright} 2023, Genentech, Inc.",

year = "2023",

doi = "10.1007/s44228-022-00023-5",

language = "English",

volume = "5",

pages = "43--51",

journal = "Clinical Hematology International",

issn = "2590-0048",

publisher = "Springer Nature",

number = "1",

}

RIS

TY - JOUR

T1 - Phase I Study of Safety and Pharmacokinetics of RO7297089, an Anti-BCMA/CD16a Bispecific Antibody, in Patients with Relapsed, Refractory Multiple Myeloma

AU - Plesner, Torben

AU - Harrison, Simon J.

AU - Quach, Hang

AU - Lee, Cindy

AU - Bryant, Adam

AU - Vangsted, Annette

AU - Estell, Jane

AU - Delforge, Michel

AU - Offner, Fritz

AU - Twomey, Patrick

AU - Choeurng, Voleak

AU - Li, Junyi

AU - Hendricks, Robert

AU - Ruppert, Shannon M.

AU - Sumiyoshi, Teiko

AU - Miller, Karen

AU - Cho, Eunpi

AU - Schjesvold, Fredrik

PY - 2023

Y1 - 2023

N2 - Introduction: This phase 1 trial assessed the safety, pharmacokinetics, and preliminary antitumor activity of RO7297089, an anti-BCMA/CD16a bispecific antibody. Methods: RO7297089 was administered weekly by intravenous infusion to patients with relapsed/refractory multiple myeloma. The starting dose was 60 mg in this dose-escalation study utilizing a modified continual reassessment method with overdose control model. Results: Overall, 27 patients were treated at doses between 60 and 1850 mg. The maximally administered dose was 1850 mg due to excipients in the formulation that did not allow for higher doses to be used. The maximum tolerated dose was not reached. The most common adverse events irrespective of grade and relationship to the drug were anemia, infusion-related reaction, and thrombocytopenia. Most common treatment-related grade ≥ 3 toxicities were ALT/AST increase and reduced lymphocyte count. Pharmacokinetic studies suggested non-linear pharmacokinetics and target-mediated drug disposition, with a trend of approaching linear pharmacokinetics at doses of 1080 mg and higher. Partial response was observed in two patients (7%), minimal response in two patients (7%), and stable disease in 14 patients (52%). Conclusions: RO7297089 was well tolerated at doses up to 1850 mg, and the efficacy data supported activity of RO7297089 in multiple myeloma. Combination with other agents may further enhance its potential as an innate immune cell engager in multiple myeloma. Trial Registration: ClinicalTrials.gov: NCT04434469; Registered June 16, 2020; https://www.clinicaltrials.gov/ct2/show/NCT04434469.

AB - Introduction: This phase 1 trial assessed the safety, pharmacokinetics, and preliminary antitumor activity of RO7297089, an anti-BCMA/CD16a bispecific antibody. Methods: RO7297089 was administered weekly by intravenous infusion to patients with relapsed/refractory multiple myeloma. The starting dose was 60 mg in this dose-escalation study utilizing a modified continual reassessment method with overdose control model. Results: Overall, 27 patients were treated at doses between 60 and 1850 mg. The maximally administered dose was 1850 mg due to excipients in the formulation that did not allow for higher doses to be used. The maximum tolerated dose was not reached. The most common adverse events irrespective of grade and relationship to the drug were anemia, infusion-related reaction, and thrombocytopenia. Most common treatment-related grade ≥ 3 toxicities were ALT/AST increase and reduced lymphocyte count. Pharmacokinetic studies suggested non-linear pharmacokinetics and target-mediated drug disposition, with a trend of approaching linear pharmacokinetics at doses of 1080 mg and higher. Partial response was observed in two patients (7%), minimal response in two patients (7%), and stable disease in 14 patients (52%). Conclusions: RO7297089 was well tolerated at doses up to 1850 mg, and the efficacy data supported activity of RO7297089 in multiple myeloma. Combination with other agents may further enhance its potential as an innate immune cell engager in multiple myeloma. Trial Registration: ClinicalTrials.gov: NCT04434469; Registered June 16, 2020; https://www.clinicaltrials.gov/ct2/show/NCT04434469.

KW - BCMA

KW - CD16a

KW - Clinical trial

KW - Multiple myeloma

KW - RO7297089

U2 - 10.1007/s44228-022-00023-5

DO - 10.1007/s44228-022-00023-5

M3 - Journal article

C2 - 36656461

AN - SCOPUS:85149774177

VL - 5

SP - 43

EP - 51

JO - Clinical Hematology International

JF - Clinical Hematology International

SN - 2590-0048

IS - 1

ER -

ID: 363273261