TY - JOUR
T1 - Indatuximab Ravtansine (BT062) Monotherapy in Patients With Relapsed and/or Refractory Multiple Myeloma
AU - Jagannath, Sundar
AU - Heffner, Leonard T.
AU - Ailawadhi, Sikander
AU - Munshi, Nikhil C.
AU - Zimmerman, Todd M.
AU - Rosenblatt, Jacalyn
AU - Lonial, Sagar
AU - Chanan-Khan, Asher
AU - Ruehle, Markus
AU - Rharbaoui, Faiza
AU - Haeder, Thomas
AU - Wartenberg-Demand, Andrea
AU - Anderson, Kenneth C.
N1 - Funding Information:
This study was sponsored by Biotest AG. Biotest has developed indatuximab ravtansine by using ADC technology licensed from ImmunoGen Inc. under a collaboration started in July 2006.
Funding Information:
S.J. participated in advisory board/received honorarium from Bristol-Meyers Squibb, Celgene, Janssen, and Novartis. L.T.H. Jr received institutional research funding from AbbVie , Genentech , and Pharmacyclics . S.A. received research funding from Pharmacyclics , declares membership on entity’s advisory committees for Amgen, Celgene, Novartis, and Takeda, and received honoraria from Amgen, Novartis, and Takeda. N.C.M. was a consultant for Biotest, Celgene, Janssen, Merck, Pfizer, Takeda, and OncoPep, and is a part owner of OncoPep. T.M.Z. was an expert witness for Novartis and received honoraria and speaker fees from Celgene and Millennium Pharmaceuticals . J.R. received research funding from Bristol-Meyer Squibb and Celgene , served on advisory summits for Bristol-Meyer Squibb, and served as a scientific advisor for Merck. S.L. was a consultant for Bristol-Meyer Squibb, Celgene, GSK, Janssen, Novartis, and Takeda. M.R., F.R., T.H. and A. W.-D. are or were employees of Biotest AG. K.C.A. received advisory board fees from Bristol-Myers Squibb , Celgene , Gilead , and Millennium Pharmaceuticals and is the scientific founder of C4 Therapeutics and OncoPep, Inc. A.C.-K. has no conflict of interest to disclose.
Funding Information:
S.J. participated in advisory board/received honorarium from Bristol-Meyers Squibb, Celgene, Janssen, and Novartis. L.T.H. Jr received institutional research funding from AbbVie, Genentech, and Pharmacyclics. S.A. received research funding from Pharmacyclics, declares membership on entity's advisory committees for Amgen, Celgene, Novartis, and Takeda, and received honoraria from Amgen, Novartis, and Takeda. N.C.M. was a consultant for Biotest, Celgene, Janssen, Merck, Pfizer, Takeda, and OncoPep, and is a part owner of OncoPep. T.M.Z. was an expert witness for Novartis and received honoraria and speaker fees from Celgene and Millennium Pharmaceuticals. J.R. received research funding from Bristol-Meyer Squibb and Celgene, served on advisory summits for Bristol-Meyer Squibb, and served as a scientific advisor for Merck. S.L. was a consultant for Bristol-Meyer Squibb, Celgene, GSK, Janssen, Novartis, and Takeda. M.R., F.R., T.H. and A. W.-D. are or were employees of Biotest AG. K.C.A. received advisory board fees from Bristol-Myers Squibb, Celgene, Gilead, and Millennium Pharmaceuticals and is the scientific founder of C4 Therapeutics and OncoPep, Inc. A.C.-K. has no conflict of interest to disclose. The authors thank the patients who participated in this study and their families, as well as the study co-investigators, research nurses, and coordinators at each of the clinical sites, and also the Independent Review Committee. This study was sponsored by Biotest AG. Biotest has developed indatuximab ravtansine by using ADC technology licensed from ImmunoGen Inc. under a collaboration started in July 2006. Medical writing and editorial assistance were provided by 4C Consultants International. The authors are grateful to Farima Barmaki-Rad, Eva Herrmann, and Christoph Uherek for their contribution to this work during the planning or conduct of the clinical trials, and for reviewing the manuscript as employees of Biotest.
Publisher Copyright:
© 2019
PY - 2019/6
Y1 - 2019/6
N2 - Background: Indatuximab ravtansine (BT062) is an antibody-drug conjugate that binds to CD138, which is overexpressed on multiple myeloma (MM) cells. Patients and Methods: We report from 2 clinical studies of patients with relapsed and/or refractory MM previously treated with an immunomodulatory drug and a proteasome inhibitor. Single- and multi-dosing schedules were investigated to define dose-limiting toxicities, maximum tolerated dose (MTD), recommended phase II dose, and to describe safety, efficacy, and pharmacokinetics. Results: In the first-in-human study, indatuximab ravtansine was administered to 32 patients on day 1 of each 21-day cycle. The MTD was 160 mg/m2. In the phase I/IIa study, indatuximab ravtansine was administered to 35 patients on days 1, 8, and 15 of each 28-day cycle, and the MTD/recommended phase II dose was 140 mg/m2. Most (88%) adverse events were grade 1 or 2, the most common being diarrhea and fatigue. There was rapid clearance of indatuximab ravtansine and no relevant accumulation. Over 75% of heavily pretreated patients achieved stable disease or better. With the multi-dose schedule, minor and partial responses occurred in 14.7% of patients, the median time to progression was 3 months, and the median overall survival was 26.7 months. Conclusion: Our data support further investigation of indatuximab ravtansine as part of a combination regimen for relapsed and/or refractory MM.
AB - Background: Indatuximab ravtansine (BT062) is an antibody-drug conjugate that binds to CD138, which is overexpressed on multiple myeloma (MM) cells. Patients and Methods: We report from 2 clinical studies of patients with relapsed and/or refractory MM previously treated with an immunomodulatory drug and a proteasome inhibitor. Single- and multi-dosing schedules were investigated to define dose-limiting toxicities, maximum tolerated dose (MTD), recommended phase II dose, and to describe safety, efficacy, and pharmacokinetics. Results: In the first-in-human study, indatuximab ravtansine was administered to 32 patients on day 1 of each 21-day cycle. The MTD was 160 mg/m2. In the phase I/IIa study, indatuximab ravtansine was administered to 35 patients on days 1, 8, and 15 of each 28-day cycle, and the MTD/recommended phase II dose was 140 mg/m2. Most (88%) adverse events were grade 1 or 2, the most common being diarrhea and fatigue. There was rapid clearance of indatuximab ravtansine and no relevant accumulation. Over 75% of heavily pretreated patients achieved stable disease or better. With the multi-dose schedule, minor and partial responses occurred in 14.7% of patients, the median time to progression was 3 months, and the median overall survival was 26.7 months. Conclusion: Our data support further investigation of indatuximab ravtansine as part of a combination regimen for relapsed and/or refractory MM.
KW - Antibody-drug conjugate
KW - CD138
KW - Monoclonal antibody
KW - Multiple-dose
KW - Syndecan-1
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U2 - 10.1016/j.clml.2019.02.006
DO - 10.1016/j.clml.2019.02.006
M3 - Article
C2 - 30930134
AN - SCOPUS:85063451981
VL - 19
SP - 372
EP - 380
JO - Clinical Lymphoma
JF - Clinical Lymphoma
SN - 2152-2669
IS - 6
ER -