2. Academic Validation
  3. First-in-Human Phase I Study of ABBV-838, an Antibody-Drug Conjugate Targeting SLAMF7/CS1 in Patients with Relapsed and Refractory Multiple Myeloma

First-in-Human Phase I Study of ABBV-838, an Antibody-Drug Conjugate Targeting SLAMF7/CS1 in Patients with Relapsed and Refractory Multiple Myeloma

  • Clin Cancer Res. 2020 May 15;26(10):2308-2317. doi: 10.1158/1078-0432.CCR-19-1431.
Ravi Vij 1,  Rajneesh Nath 2,  Daniel E H Afar 2,  María-Victoria Mateos 3,  Jesús G Berdeja 4,  Marc S Raab 5,  Andreas Guenther 6,  Joaquín Martínez-López 7,  Andrzej J Jakubowiak 8,  Xavier Leleu 9,  Katja Weisel 10,  Shekman Wong 2,  Scott Gulbranson 2,  James P Sheridan 2,  Anita Reddy 2,  Bruno Paiva 11,  Anil Singhal 2,  Jesús F San-Miguel 11,  Philippe Moreau 12
Affiliations

Affiliations

  • 1 Washington University School of Medicine, St. Louis, Missouri. rvij@wustl.edu.
  • 2 AbbVie Inc., Redwood City, California.
  • 3 Hospital Universitario de Salamanca, Salamanca/IBSAL/CCI-IBMCC (USAL-CSIC), Salamanca, Spain.
  • 4 Sarah Cannon Research Institute, Nashville, Tennessee.
  • 5 Universitaetsklinikum Heidelberg, Heidelberg, Germany.
  • 6 Universitaetsklinikum Schleswig-Holstein, Kiel, Germany.
  • 7 Hospital Universitario 12 de Octubre, Complutense University, CNIO, CIBERONC, Madrid, Spain.
  • 8 University of Chicago Medical Center, Chicago, Illinois.
  • 9 CHRU de Lille, Hôpital Claude Huriez, Lille Cedex, France.
  • 10 University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • 11 Clinica Universidad de Navarra, CIMA, IDISNA, CIBERONC, Pamplona-Navarra, Spain.
  • 12 CHU de Nantes, Hôtel Dieu - HME, Nantes Cedex 1, France.
PMID: 31969330 DOI: 10.1158/1078-0432.CCR-19-1431
Abstract

Purpose: ABBV-838 is an antibody-drug conjugate targeting a unique epitope of CD2 subset 1, a cell-surface glycoprotein expressed on multiple myeloma cells. This phase I/Ib first-in-human, dose-escalation study (trial registration ID: NCT02462525) evaluated the safety, pharmacokinetics, and preliminary activity of ABBV-838 in patients with relapsed and refractory multiple myeloma (RRMM).

Patients and methods: Eligible patients (≥18 years) received ABBV-838 (3+3 design) intravenously starting from 0.6 mg/kg up to 6.0 mg/kg for 3-week dosing intervals (Q3W). Patients could continue ABBV-838 for up to 24 months. Assessment of alternate dosing intervals (Q1W and Q2W) was conducted in parallel.

Results: As of March 2017, 75 patients received at least one dose of ABBV-838. The most common any-grade treatment-emergent adverse events (TEAE) were neutropenia and anemia (28.0% each), fatigue (26.7%), and nausea (25.3%). Grade 3/4/5 TEAEs were reported in 73.3% of patients across all treatment groups; most common were neutropenia (20.0%), anemia (18.7%), and leukopenia (13.3%). Grade 3/4/5 ABBV-838-related TEAEs were reported by 40.0% of patients across all treatment groups. Overall, 4.0% of patients experienced TEAEs leading to death, none ABBV-838 related. The MTD was not reached; the selected recommended dose for the expansion cohort was 5.0 mg/kg Q3W. Pharmacokinetic analysis showed that exposure was approximately dose proportional. The overall response rate was 10.7%; very good partial responses and partial responses were achieved by 2 (2.7%) and 6 (8.0%) patients, respectively.

Conclusions: These results demonstrate that ABBV-838 is safe and well-tolerated in patients with RRMM with a very limited efficacy.

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