A Phase I First-in-Human Study of ABBV-383, a B-Cell Maturation Antigen × CD3 Bispecific T-Cell Redirecting Antibody, in Patients With Relapsed/Refractory Multiple Myeloma

  • J Clin Oncol. 2022 Nov 1;40(31):3576-3586. doi: 10.1200/JCO.22.01504.
Anita D'Souza  1 ,  Nina Shah  2 ,  Cesar Rodriguez  3 ,  Peter M Voorhees  4 ,  Katja Weisel  5 ,  Orlando F Bueno  6 ,  Rajvineeth K Pothacamury  6 ,  Kevin J Freise  6 ,  Susan Yue  6 ,  Jeremy A Ross  6 ,  Akshanth R Polepally  6 ,  Chetasi Talati  6 ,  Shane Lee  6 ,  Ziyi Jin  6 ,  Ben Buelow  7 ,  Ravi Vij  8 ,  Shaji Kumar  9
Affiliations
  • 1. Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.
  • 2. Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA.
  • 3. Medical Oncology and Hematology, Wake Forest University School of Medicine, Winston-Salem, NC.
  • 4. Plasma Cell Disorders Division, Department of Hematologic Oncology & Blood Disorders, Levine Cancer Institute, Atrium Health/Wake Forest Baptist, Charlotte, NC.
  • 5. Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • 6. AbbVie, Inc, North Chicago, IL.
  • 7. TeneoBio, Inc, Newark, CA.
  • 8. Washington University School of Medicine, St Louis, MO.
  • 9. Department of Hematology, Mayo Clinic, Rochester, MN.
PMID: 36029527 DOI: 10.1200/JCO.22.01504
Abstract

Purpose: ABBV-383, a B-cell maturation antigen × CD3 T-cell engaging bispecific antibody, has demonstrated promising results in an ongoing first-in-human phase I study (ClinicalTrials.gov identifier: NCT03933735) in patients with relapsed/refractory multiple myeloma (RRMM). Herein, we report safety and efficacy outcomes of this phase I dose escalation/expansion study.

Methods: Patients with RRMM (≥ three prior lines including a Proteasome Inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody) were eligible. ABBV-383 was administered intravenously over 1-2 hours once every 3 weeks, without any step dosing. A 3 + 3 design with backfilling for dose escalation was used (intrapatient escalation to highest safe dose permitted) followed by initiation of dose expansion.

Results: As of January 8, 2022, 124 patients (dose escalation [0.025-120 mg], n = 73; dose expansion [60 mg], n = 51) have received ABBV-383; median age was 68 years (range, 35-92 years). The most common hematologic treatment-emergent adverse events (TEAEs) were neutropenia (all grades: 37%) and anemia (29%). The most common nonhematologic TEAEs were cytokine release syndrome (57%) and fatigue (30%). Seven deaths from TEAEs were reported with all considered unrelated to study drug by the investigator. For all efficacy-evaluable patients (n = 122; all doses), the objective response rate (ORR) was 57% and very good partial response (VGPR) or better (≥ VGPR) rate was 43%. In the 60 mg dose expansion cohort (n = 49), the ORR and ≥ VGPR rates were 59% and 39%, respectively; and in the ≥ 40 mg dose escalation plus dose expansion cohorts (n = 79) were 68% and 54%, respectively.

Conclusion: ABBV-383 in patients with RRMM was well tolerated with an ORR of 68% at doses ≥ 40 mg. This novel therapy's promising preliminary antitumor activity in heavily pretreated patients warrants further clinical evaluation.

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