Scientific publications
First-in-Human Phase 1 Study of ABBV-838, an Antibody-Drug Conjugate Targeting SLAMF7/CS1 in Patients With Relapsed and Refractory Multiple Myeloma. Scientific Publication
Vij R (1), Nath R (2), Afar DEH (3), Mateos MV (4), Berdeja JG (5), Raab MS (6), Guenther A (7), Martinez-Lopez J (8), Jakubowiak AJ (9), Leleu X (10), Weisel K 11, Wong S (12), Gulbranson S (13), Sheridan JP (14), Reddy A (12), Paiva B 15, Singhal A (16), San-Miguel JF (17), Moreau P (18).
PURPOSE:
ABBV-838 is an antibody-drug conjugate targeting a unique epitope of CD2 subset 1, a cell-surface glycoprotein expressed on multiple myeloma (MM) cells. This phase 1/1b 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 (RR) MM.
EXPERIMENTAL DESIGN:
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) were 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 (TEAEs) 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 maximum tolerated dose 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 two (2.7%) and six (8.0%) patients, respectively.
CONCLUSIONS:
These results demonstrate that ABBV-838 is safe and well tolerated in patients with RR MM with a very limited efficacy.
CITATION Clin Cancer Res. 2020 Jan 22. pii: clincanres.1431.2019. doi: 10.1158/1078-0432.CCR-19-1431
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