brentuximab vedotin

Ligand id: 6772

Name: brentuximab vedotin

No information available.
Summary of Clinical Use
Brentuximab vedotin is an anti-neoplastic agent used in the treatment of Hodgkin's lymphoma [6] and systemic anaplastic large cell lymphoma. Several clinical trials are evaluating the combination of brentuximab vedotin with immune checkpoint inhibitors, to assess any synergistic effects as a result of dual targeting. Checkpoint inhibitors being investigated in this way include nivolumab and pembrolizumab (both anti-PD-1), and ipilimumab (anti-CTLA4). Brentuximab vedotin + pembrolizumab (NCT02684292) and brentuximab vedotin + nivolumab (NCT03138499) are both Phase 3 studies in patients with relapsed/refractory classical Hodgkin's lymphoma.

Expanded approvals:
In November 2017, the FDA approved brentuximab vedotin for the treatment of adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy, following review of results from the Phase 3 ALCANZA trial (NCT01578499) [3]. In March 2018, the FDA approved the use of brentuximab vedotin for the treatment of patients with previously untreated stage III or IV classical Hodgkin lymphoma (cHL) in combination with chemotherapy. This expansion was based on results from the ECHELON-1 clinical trial (NCT01712490) [2,7].
Mechanism Of Action and Pharmacodynamic Effects
This drug efficiently delivers a highly cytotoxic drug to a specific set of cells, namely CD30 +ve cancer cells. Upon binding to cell surface antigen the conjugate is rapidly internalised and the cytotoxic portion (MMAE) is cleaved. This then travels to the nucleus where it binds β-tubulin and disrupts microtubule formation, thereby causing cell cycle arrest and subsequent cell death. MMAE seems to only bind to β-tubulin [5], at a similar location to the Vinca domain.
External links