First-in-Human Phase 1 Study of ABBV-838, an Antibody-Drug Conjugate Targeting SLAMF7/CS1 in Patients With Relapsed and Refractory Multiple Myeloma
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).
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.
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.
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.
These results demonstrate that ABBV-838 is safe and well tolerated in patients with RR MM with a very limited efficacy.
CITA DEL ARTÍCULO Clin Cancer Res. 2020 Jan 22. pii: clincanres.1431.2019. doi: 10.1158/1078-0432.CCR-19-1431