brentuximab vedotin

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Ligands
brentuximab vedotin

GtoPdb Ligand ID: 6772

Synonyms: Adcetris® | anti-CD30 ADC SGN-35 | SGN 35

brentuximab vedotin is an approved drug (FDA (2011), EMA (2012))

Comment: Antibody-drug conjugate (ADC) that combines an anti-CD30 antibody and the drug monomethyl auristatin E (MMAE). The PubChem ID for the MMAE component compound is CID 11542188. The invention of this ADC is claimed in patent US7090843 [4] and the original article describing the parent antibody (C10 or AC10) is [1].
Annotated peptide sequences for this antibody are available from its IMGT/mAb-DB record.

No information available.

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]. November 2018 saw further expansion of approval for the use of brentuximab vedotin plus chemotherapy for adult patients who are newly diagnosed with CD30-expressing peripheral T-cell lymphomas.

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]. November 2018 saw further expansion of approval for the use of brentuximab vedotin plus chemotherapy for adult patients who are newly diagnosed with CD30-expressing peripheral T-cell lymphomas.

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.

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.

Clinical Trials
Clinical Trial ID	Title	Type	Source	Comment	References
NCT01578499	A Phase 3 Trial of Brentuximab Vedotin(SGN-35) Versus Physician's Choice (Methotrexate or Bexarotene) in Participants With CD30-Positive Cutaneous T-Cell Lymphoma (ALCANZA Study)	Phase 3 Interventional	Takeda
NCT01712490	A Frontline Therapy Trial in Participants With Advanced Classical Hodgkin Lymphoma	Phase 3 Interventional	Takeda
NCT02684292	Study of Pembrolizumab (MK-3475) vs. Brentuximab Vedotin in Participants With Relapsed or Refractory Classical Hodgkin Lymphoma (MK-3475-204/KEYNOTE-204)	Phase 3 Interventional	Merck Sharp & Dohme Corp.
NCT03138499	A Study of Nivolumab Plus Brentuximab Vedotin Versus Brentuximab Vedotin Alone in Patients With Advanced Stage Classical Hodgkin Lymphoma, Who Are Relapsed/ Refractory or Who Are Not Eligible for Autologous Stem Cell Transplant,	Phase 3 Interventional	Bristol-Myers Squibb

External links
For extended ADME data see the following: Electronic Medicines Compendium (eMC) Drugs.com European Medicines Agency (EMA)

External links

For extended ADME data see the following:

Electronic Medicines Compendium (eMC)
Drugs.com
European Medicines Agency (EMA)