Phase 1 study of tabalumab, a human anti-B-cell activating factor antibody, and bortezomib in patients with relapsed/refractory multiple myeloma

Noopur S. Raje, Edward A. Faber, Paul G. Richardson, Gary Schiller, Raymond Hohl, Adam D. Cohen, Andres Forero, Susan Carpenter, Tuan S. Nguyen, Ilaria Conti, Christopher J. Kaiser, Damien M. Cronier, James E. Wooldridge, Kenneth C. Anderson

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Abstract

Purpose: Tabalumab, a human mAb that neutralizes B-cell-activating factor (BAFF), demonstrated antitumor activity in xenograft models of multiple myeloma. Here we report on a phase I study of relapsed/refractory multiple myeloma patients in which the primary objective was to identify a tolerable and potentially efficacious dose of tabalumab when combined with bortezomib. Experimental Design: Forty-eight patients were enrolled; 20 to the dose-escalation cohort, and 28 to cohort expansion in which a dose of 100 mg of tabalumab was evaluated. All patients had received either prior bortezomib or an immunomodulatory drug; the median number of prior therapies was 3. Bortezomib was administered intravenously on days 1, 4, 8, and 11 of a 21-day schedule. Tabalumab was given every 21 days for 3 cycles, then every 42 days thereafter. Results: The most common grade 3/4 toxicities included thrombocytopenia, neutropenia, pneumonia, and peripheral sensory neuropathy. There were no dose-limiting toxicities, and themaximum tolerated dose was not reached. Pharmacokinetic data suggested serum exposure increased in a greater than doseproportional manner up to a dose of 100 mg. Out of 46 evaluable patients, 20 had confirmed responses. The median time to progression (9 patients censored) was 4.8 months, and the median response duration (4 patients censored) was 7.2 months. Conclusions: A dose of 100 mg tabalumab in combination with bortezomib was well tolerated and active and is currently under further investigation. Clin Cancer Res; 22(23); 5688-95.

Original languageEnglish (US)
Pages (from-to)5688-5695
Number of pages8
JournalClinical Cancer Research
Volume22
Issue number23
DOIs
StatePublished - Dec 1 2016

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B-Cell Activating Factor
Multiple Myeloma
Antibodies
Peripheral Nervous System Diseases
Neutropenia
Heterografts
Thrombocytopenia
Bortezomib
tabalumab
Pneumonia
Appointments and Schedules
Research Design
Pharmacokinetics
Serum
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Raje, Noopur S. ; Faber, Edward A. ; Richardson, Paul G. ; Schiller, Gary ; Hohl, Raymond ; Cohen, Adam D. ; Forero, Andres ; Carpenter, Susan ; Nguyen, Tuan S. ; Conti, Ilaria ; Kaiser, Christopher J. ; Cronier, Damien M. ; Wooldridge, James E. ; Anderson, Kenneth C. / Phase 1 study of tabalumab, a human anti-B-cell activating factor antibody, and bortezomib in patients with relapsed/refractory multiple myeloma. In: Clinical Cancer Research. 2016 ; Vol. 22, No. 23. pp. 5688-5695.
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abstract = "Purpose: Tabalumab, a human mAb that neutralizes B-cell-activating factor (BAFF), demonstrated antitumor activity in xenograft models of multiple myeloma. Here we report on a phase I study of relapsed/refractory multiple myeloma patients in which the primary objective was to identify a tolerable and potentially efficacious dose of tabalumab when combined with bortezomib. Experimental Design: Forty-eight patients were enrolled; 20 to the dose-escalation cohort, and 28 to cohort expansion in which a dose of 100 mg of tabalumab was evaluated. All patients had received either prior bortezomib or an immunomodulatory drug; the median number of prior therapies was 3. Bortezomib was administered intravenously on days 1, 4, 8, and 11 of a 21-day schedule. Tabalumab was given every 21 days for 3 cycles, then every 42 days thereafter. Results: The most common grade 3/4 toxicities included thrombocytopenia, neutropenia, pneumonia, and peripheral sensory neuropathy. There were no dose-limiting toxicities, and themaximum tolerated dose was not reached. Pharmacokinetic data suggested serum exposure increased in a greater than doseproportional manner up to a dose of 100 mg. Out of 46 evaluable patients, 20 had confirmed responses. The median time to progression (9 patients censored) was 4.8 months, and the median response duration (4 patients censored) was 7.2 months. Conclusions: A dose of 100 mg tabalumab in combination with bortezomib was well tolerated and active and is currently under further investigation. Clin Cancer Res; 22(23); 5688-95.",
author = "Raje, {Noopur S.} and Faber, {Edward A.} and Richardson, {Paul G.} and Gary Schiller and Raymond Hohl and Cohen, {Adam D.} and Andres Forero and Susan Carpenter and Nguyen, {Tuan S.} and Ilaria Conti and Kaiser, {Christopher J.} and Cronier, {Damien M.} and Wooldridge, {James E.} and Anderson, {Kenneth C.}",
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Raje, NS, Faber, EA, Richardson, PG, Schiller, G, Hohl, R, Cohen, AD, Forero, A, Carpenter, S, Nguyen, TS, Conti, I, Kaiser, CJ, Cronier, DM, Wooldridge, JE & Anderson, KC 2016, 'Phase 1 study of tabalumab, a human anti-B-cell activating factor antibody, and bortezomib in patients with relapsed/refractory multiple myeloma', Clinical Cancer Research, vol. 22, no. 23, pp. 5688-5695. https://doi.org/10.1158/1078-0432.CCR-16-0201

Phase 1 study of tabalumab, a human anti-B-cell activating factor antibody, and bortezomib in patients with relapsed/refractory multiple myeloma. / Raje, Noopur S.; Faber, Edward A.; Richardson, Paul G.; Schiller, Gary; Hohl, Raymond; Cohen, Adam D.; Forero, Andres; Carpenter, Susan; Nguyen, Tuan S.; Conti, Ilaria; Kaiser, Christopher J.; Cronier, Damien M.; Wooldridge, James E.; Anderson, Kenneth C.

In: Clinical Cancer Research, Vol. 22, No. 23, 01.12.2016, p. 5688-5695.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase 1 study of tabalumab, a human anti-B-cell activating factor antibody, and bortezomib in patients with relapsed/refractory multiple myeloma

AU - Raje, Noopur S.

AU - Faber, Edward A.

AU - Richardson, Paul G.

AU - Schiller, Gary

AU - Hohl, Raymond

AU - Cohen, Adam D.

AU - Forero, Andres

AU - Carpenter, Susan

AU - Nguyen, Tuan S.

AU - Conti, Ilaria

AU - Kaiser, Christopher J.

AU - Cronier, Damien M.

AU - Wooldridge, James E.

AU - Anderson, Kenneth C.

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Purpose: Tabalumab, a human mAb that neutralizes B-cell-activating factor (BAFF), demonstrated antitumor activity in xenograft models of multiple myeloma. Here we report on a phase I study of relapsed/refractory multiple myeloma patients in which the primary objective was to identify a tolerable and potentially efficacious dose of tabalumab when combined with bortezomib. Experimental Design: Forty-eight patients were enrolled; 20 to the dose-escalation cohort, and 28 to cohort expansion in which a dose of 100 mg of tabalumab was evaluated. All patients had received either prior bortezomib or an immunomodulatory drug; the median number of prior therapies was 3. Bortezomib was administered intravenously on days 1, 4, 8, and 11 of a 21-day schedule. Tabalumab was given every 21 days for 3 cycles, then every 42 days thereafter. Results: The most common grade 3/4 toxicities included thrombocytopenia, neutropenia, pneumonia, and peripheral sensory neuropathy. There were no dose-limiting toxicities, and themaximum tolerated dose was not reached. Pharmacokinetic data suggested serum exposure increased in a greater than doseproportional manner up to a dose of 100 mg. Out of 46 evaluable patients, 20 had confirmed responses. The median time to progression (9 patients censored) was 4.8 months, and the median response duration (4 patients censored) was 7.2 months. Conclusions: A dose of 100 mg tabalumab in combination with bortezomib was well tolerated and active and is currently under further investigation. Clin Cancer Res; 22(23); 5688-95.

AB - Purpose: Tabalumab, a human mAb that neutralizes B-cell-activating factor (BAFF), demonstrated antitumor activity in xenograft models of multiple myeloma. Here we report on a phase I study of relapsed/refractory multiple myeloma patients in which the primary objective was to identify a tolerable and potentially efficacious dose of tabalumab when combined with bortezomib. Experimental Design: Forty-eight patients were enrolled; 20 to the dose-escalation cohort, and 28 to cohort expansion in which a dose of 100 mg of tabalumab was evaluated. All patients had received either prior bortezomib or an immunomodulatory drug; the median number of prior therapies was 3. Bortezomib was administered intravenously on days 1, 4, 8, and 11 of a 21-day schedule. Tabalumab was given every 21 days for 3 cycles, then every 42 days thereafter. Results: The most common grade 3/4 toxicities included thrombocytopenia, neutropenia, pneumonia, and peripheral sensory neuropathy. There were no dose-limiting toxicities, and themaximum tolerated dose was not reached. Pharmacokinetic data suggested serum exposure increased in a greater than doseproportional manner up to a dose of 100 mg. Out of 46 evaluable patients, 20 had confirmed responses. The median time to progression (9 patients censored) was 4.8 months, and the median response duration (4 patients censored) was 7.2 months. Conclusions: A dose of 100 mg tabalumab in combination with bortezomib was well tolerated and active and is currently under further investigation. Clin Cancer Res; 22(23); 5688-95.

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