First-in-Human Phase I Study of ABBV-838, an Antibody-Drug Conjugate Targeting SLAMF7/CS1 in Patients with Relapsed and Refractory Multiple Myeloma
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First-in-Human Phase I Study of ABBV-838, an Antibody-Drug Conjugate Targeting SLAMF7/CS1 in Patients with Relapsed and Refractory Multiple Myeloma. / Vij, Ravi; Nath, Rajneesh; Afar, Daniel E H; Mateos, Maria Victoria; Berdeja, Jesus G; Raab, Marc S; Guenther, Andreas; Martinez-Lopez, Joaquin; Jakubowiak, Andrzej J; Leleu, Xavier; Weisel, Katja; Wong, Shekman; Gulbranson, Scott; Sheridan, James P; Reddy, Anita; Paiva, Bruno; Singhal, Anil; San-Miguel, Jesus F; Moreau, Philippe.
in: CLIN CANCER RES, Jahrgang 26, Nr. 10, 15.05.2020, S. 2308-2317.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - First-in-Human Phase I Study of ABBV-838, an Antibody-Drug Conjugate Targeting SLAMF7/CS1 in Patients with Relapsed and Refractory Multiple Myeloma
AU - Vij, Ravi
AU - Nath, Rajneesh
AU - Afar, Daniel E H
AU - Mateos, Maria Victoria
AU - Berdeja, Jesus G
AU - Raab, Marc S
AU - Guenther, Andreas
AU - Martinez-Lopez, Joaquin
AU - Jakubowiak, Andrzej J
AU - Leleu, Xavier
AU - Weisel, Katja
AU - Wong, Shekman
AU - Gulbranson, Scott
AU - Sheridan, James P
AU - Reddy, Anita
AU - Paiva, Bruno
AU - Singhal, Anil
AU - San-Miguel, Jesus F
AU - Moreau, Philippe
N1 - Copyright ©2020, American Association for Cancer Research.
PY - 2020/5/15
Y1 - 2020/5/15
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Antibodies, Monoclonal, Humanized/pharmacokinetics
KW - Cohort Studies
KW - Drug Resistance, Neoplasm
KW - Female
KW - Follow-Up Studies
KW - Humans
KW - Immunoconjugates/pharmacokinetics
KW - Male
KW - Middle Aged
KW - Multiple Myeloma/drug therapy
KW - Neoplasm Recurrence, Local/drug therapy
KW - Prognosis
KW - Salvage Therapy
KW - Signaling Lymphocytic Activation Molecule Family/antagonists & inhibitors
KW - Tissue Distribution
U2 - 10.1158/1078-0432.CCR-19-1431
DO - 10.1158/1078-0432.CCR-19-1431
M3 - SCORING: Journal article
C2 - 31969330
VL - 26
SP - 2308
EP - 2317
JO - CLIN CANCER RES
JF - CLIN CANCER RES
SN - 1078-0432
IS - 10
ER -