Open Access

A phase I dose-escalation study to a predefined dose of a transforming growth factor-β1 monoclonal antibody (TβM1) in patients with metastatic cancer

  • Authors:
    • Allen Cohn
    • Michael M. Lahn
    • Kristen E. Williams
    • Ann L. Cleverly
    • Celine Pitou
    • Sunil K. Kadam
    • Mark W. Farmen
    • Durisala Desaiah
    • Robert Raju
    • Paul Conkling
    • Donald Richards
  • View Affiliations

  • Published online on: September 26, 2014     https://doi.org/10.3892/ijo.2014.2679
  • Pages: 2221-2231
  • Copyright: © Cohn et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Transforming growth factor β (TGF-β) plays an important role in cancer. Monoclonal antibodies (mAb) designed to specifically block the TGF-β ligands, are expected to inhibit tumor progression in patients with metastatic cancer. TβM1 is a humanized mAb optimized for neutralizing activity against TGF-β1. The objective of this clinical trial was to assess the safety and tolerability of TβM1 in patients with metastatic cancer. In this phase I, uncontrolled, non‑randomized, dose-escalation study, 18 eligible adult patients who had measurable disease per RECIST and a performance status of ≤2 on the ECOG scale were administered TβM1 intravenously over 10 min at doses of 20, 60, 120 and 240 mg on day 1 of each 28-day cycle. Safety was assessed by adverse events (as defined by CTCAE version 3.0) and possible relationship to study drug, dose-limiting toxicities and laboratory changes. Systemic drug exposure and pharmacodynamic (PD) parameters were assessed. TβM1 was safe when administered once monthly. The pharmacokinetic (PK) profile was consistent with a mAb with a mean elimination half-life approximately 9 days. Although anticipated changes in PD markers such as serum VEGF, bFGF and mRNA expression of SMAD7 were observed in whole-blood, suggesting activity of TβM1 on the targeted pathway, these changes were not consistent to represent a PD effect. Additionally, despite the presence of an activated TGF-β1 expression signature in patients' whole blood, the short dosing duration did not translate into significant antitumor effect in the small number of patients investigated in this study.
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December-2014
Volume 45 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Cohn A, Lahn MM, Williams KE, Cleverly AL, Pitou C, Kadam SK, Farmen MW, Desaiah D, Raju R, Conkling P, Conkling P, et al: A phase I dose-escalation study to a predefined dose of a transforming growth factor-β1 monoclonal antibody (TβM1) in patients with metastatic cancer. Int J Oncol 45: 2221-2231, 2014
APA
Cohn, A., Lahn, M.M., Williams, K.E., Cleverly, A.L., Pitou, C., Kadam, S.K. ... Richards, D. (2014). A phase I dose-escalation study to a predefined dose of a transforming growth factor-β1 monoclonal antibody (TβM1) in patients with metastatic cancer. International Journal of Oncology, 45, 2221-2231. https://doi.org/10.3892/ijo.2014.2679
MLA
Cohn, A., Lahn, M. M., Williams, K. E., Cleverly, A. L., Pitou, C., Kadam, S. K., Farmen, M. W., Desaiah, D., Raju, R., Conkling, P., Richards, D."A phase I dose-escalation study to a predefined dose of a transforming growth factor-β1 monoclonal antibody (TβM1) in patients with metastatic cancer". International Journal of Oncology 45.6 (2014): 2221-2231.
Chicago
Cohn, A., Lahn, M. M., Williams, K. E., Cleverly, A. L., Pitou, C., Kadam, S. K., Farmen, M. W., Desaiah, D., Raju, R., Conkling, P., Richards, D."A phase I dose-escalation study to a predefined dose of a transforming growth factor-β1 monoclonal antibody (TβM1) in patients with metastatic cancer". International Journal of Oncology 45, no. 6 (2014): 2221-2231. https://doi.org/10.3892/ijo.2014.2679