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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

Standard

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, Vol. 26, No. 10, 15.05.2020, p. 2308-2317.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Vij, R, Nath, R, Afar, DEH, Mateos, MV, Berdeja, JG, Raab, MS, Guenther, A, Martinez-Lopez, J, Jakubowiak, AJ, Leleu, X, Weisel, K, Wong, S, Gulbranson, S, Sheridan, JP, Reddy, A, Paiva, B, Singhal, A, San-Miguel, JF & Moreau, P 2020, '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, vol. 26, no. 10, pp. 2308-2317. https://doi.org/10.1158/1078-0432.CCR-19-1431

APA

Vij, R., Nath, R., Afar, D. E. H., Mateos, M. V., Berdeja, J. G., Raab, M. S., Guenther, A., Martinez-Lopez, J., Jakubowiak, A. J., Leleu, X., Weisel, K., Wong, S., Gulbranson, S., Sheridan, J. P., Reddy, A., Paiva, B., Singhal, A., San-Miguel, J. F., & Moreau, P. (2020). 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, 26(10), 2308-2317. https://doi.org/10.1158/1078-0432.CCR-19-1431

Vancouver

Vij R, Nath R, Afar DEH, Mateos MV, Berdeja JG, Raab MS et al. 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. https://doi.org/10.1158/1078-0432.CCR-19-1431

Bibtex

@article{76d29cf819b54f49823bd882c066ae5a,
title = "First-in-Human Phase I Study of ABBV-838, an Antibody-Drug Conjugate Targeting SLAMF7/CS1 in Patients with Relapsed and Refractory Multiple Myeloma",
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.",
keywords = "Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized/pharmacokinetics, Cohort Studies, Drug Resistance, Neoplasm, Female, Follow-Up Studies, Humans, Immunoconjugates/pharmacokinetics, Male, Middle Aged, Multiple Myeloma/drug therapy, Neoplasm Recurrence, Local/drug therapy, Prognosis, Salvage Therapy, Signaling Lymphocytic Activation Molecule Family/antagonists & inhibitors, Tissue Distribution",
author = "Ravi Vij and Rajneesh Nath and Afar, {Daniel E H} and Mateos, {Maria Victoria} and Berdeja, {Jesus G} and Raab, {Marc S} and Andreas Guenther and Joaquin Martinez-Lopez and Jakubowiak, {Andrzej J} and Xavier Leleu and Katja Weisel and Shekman Wong and Scott Gulbranson and Sheridan, {James P} and Anita Reddy and Bruno Paiva and Anil Singhal and San-Miguel, {Jesus F} and Philippe Moreau",
note = "Copyright {\textcopyright}2020, American Association for Cancer Research.",
year = "2020",
month = may,
day = "15",
doi = "10.1158/1078-0432.CCR-19-1431",
language = "English",
volume = "26",
pages = "2308--2317",
journal = "CLIN CANCER RES",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "10",

}

RIS

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 -