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

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

doi:10.1007/s44228-022-00023-5

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

Clin Hematol Int. 2023 Mar;5(1):43-51. doi: 10.1007/s44228-022-00023-5. Epub 2023 Jan 19.

Authors

Torben Plesner¹, Simon J Harrison², Hang Quach³, Cindy Lee⁴, Adam Bryant⁵, Annette Vangsted⁶, Jane Estell⁷, Michel Delforge⁸, Fritz Offner⁹, Patrick Twomey¹⁰, Voleak Choeurng¹¹, Junyi Li¹⁰, Robert Hendricks¹⁰, Shannon M Ruppert¹⁰, Teiko Sumiyoshi¹⁰, Karen Miller¹⁰, Eunpi Cho¹⁰, Fredrik Schjesvold^{11

12}

Affiliations

¹ Vejle Hospital, University of Southern Denmark, Vejle, Denmark. Torben.Plesner@rsyd.dk.
² Peter MacCallum Cancer Center, Royal Melbourne Hospital, Melbourne and Sir Peter MacCallum Dept of Oncology University of Melbourne, Parkville, Australia.
³ St. Vincent's Hospital Melbourne, University of Melbourne, Melbourne, Australia.
⁴ Royal Adelaide Hospital, Adelaide, Australia.
⁵ Liverpool Hospital, Sydney, Australia.
⁶ Department of Hematology, Rigshopitalet, Copenhagen, Denmark.
⁷ Concord Repatriation General Hospital, Concord, Australia.
⁸ University Hospitals Leuven, Louvain, Belgium.
⁹ Ghent University, Ghent, Belgium.
¹⁰ Genentech, Inc., South San Francisco, CA, USA.
¹¹ Oslo Myeloma Center, Department of Hematology, Oslo University Hospital, Oslo, Norway.
¹² KG Jebsen Center for B Cell Malignancies, University of Oslo, Oslo, Norway.

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.

Associated data

ClinicalTrials.gov/NCT04434469