Brentuximab vedotin: clinical updates and practical guidance

Yi, Jun; Kim, Seok Jin; Kim, Won Seog

doi:10.5045/br.2017.52.4.243

Cited by 45 publications

(44 citation statements)

References 95 publications

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“…Other ADCs that have been approved are brentuximab vedotin (Adcetris; Seattle Genetics, Inc.; CD30 targeted; ref. 13) and inotuzumab ozogamicin (Besponsa; Pfizer; CD22 targeted; ref. 14), which were approved for hematologic malignancies, and trastuzumab emtansine (Kadcyla; Genentech; HER2 targeted), which was approved for breast cancer (15).…”

Section: Overview Of Adcs In Clinical Developmentmentioning

confidence: 99%

“…Clear clinical benefits have been demonstrated with all 4 approved ADCs; however, each has reported toxicity profiles that are specific to its cytotoxic warhead and, therefore, they cannot be differentiated from standard-of-care chemotherapies (13)(14)(15) in terms of safety. Regardless of the obstacles, there is intense interest in developing ADCs-approximately 80 ADC candidates are reportedly in clinical development, with nearly 600 clinical trials ongoing-and it is likely that several new ADCs will be approved over the next few years ( Fig.…”

Section: Overview Of Adcs In Clinical Developmentmentioning

confidence: 99%

“…ADCs have been shown to be effective in hematologyoncology indications, including three of the four approved ADCs (gemtuzumab ozogamicin, brentuximab vedotin, and inotuzumab ozogamicin; refs. [10][11][12][13][14]; establishing a means of monitoring the changes in tumor burden in bone marrow without invasive sampling could help make development in these indications more efficient and less burdensome for patients.…”

Section: Biomarkers To Capture Response Signals Early and Monitor Thementioning

confidence: 99%

See 2 more Smart Citations

Antibody–Drug Conjugates: Future Directions in Clinical and Translational Strategies to Improve the Therapeutic Index

Coats

Williams

Kebble

et al. 2019

Clinical Cancer Research

243

171

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Since the first approval of gemtuzumab ozogamicin (Mylotarg; Pfizer; CD33 targeted), two additional antibodydrug conjugates (ADC), brentuximab vedotin (Adcetris; Seattle Genetics, Inc.; CD30 targeted) and inotuzumab ozogamicin (Besponsa; Pfizer; CD22 targeted), have been approved for hematologic cancers and 1 ADC, trastuzumab emtansine (Kadcyla; Genentech; HER2 targeted), has been approved to treat breast cancer. Despite a clear clinical benefit being demonstrated for all 4 approved ADCs, the toxicity profiles are comparable with those of standard-of-care chemotherapeutics, with dose-limiting toxicities associated with the mecha-nism of activity of the cytotoxic warhead. However, the enthusiasm to develop ADCs has not been dampened; approximately 80 ADCs are in clinical development in nearly 600 clinical trials, and 2 to 3 novel ADCs are likely to be approved within the next few years. While the promise of a more targeted chemotherapy with less toxicity has not yet been realized with ADCs, improvements in technology combined with a wealth of clinical data are helping to shape the future development of ADCs. In this review, we discuss the clinical and translational strategies associated with improving the therapeutic index for ADCs.

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Section: Overview Of Adcs In Clinical Developmentmentioning

confidence: 99%

Section: Overview Of Adcs In Clinical Developmentmentioning

confidence: 99%

Section: Biomarkers To Capture Response Signals Early and Monitor Thementioning

confidence: 99%

See 1 more Smart Citation

Antibody–Drug Conjugates: Future Directions in Clinical and Translational Strategies to Improve the Therapeutic Index

Coats

Williams

Kebble

et al. 2019

Clinical Cancer Research

243

171

View full text Add to dashboard Cite

show abstract

“…For brentuximab vedotin, a cathepsin cleavable valine-citrulline linker was chosen, as it met these criteria and, moreover, allowed for better water solubility and satisfactory pharmacokinetics of the drug (Doronina et al, 2003). Recognition showed a reduced toxicity by nearly 1,000 times, thus displaying an antigen-dependent effect (Francisco et al, 2003;Yi, Kim, & Kim, 2017 (Younes, 2011). Furthermore, Phase II trials in patients with Hodgkin's lymphoma and ALCL showed ORR of 73% (with 32% complete responses) and 86% (with 57% complete responses) respectively (Younes, Yasothan, & Kirkpatrick, 2012).…”

Section: Warhead Drugs (Brentuximab Vedotin Adcetris): Special Delmentioning

confidence: 99%

Enriching cancer pharmacology with drugs of marine origin

Jimenez¹,

Wilke

Branco

et al. 2019

British J Pharmacology

104

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Marine natural products have proven, over the last half-century, to be effective biological modulators. These molecules have revealed new targets for cancer therapy as well as dissimilar modes of action within typical classes of drugs. In this scenario, innovation from marine-based pharmaceuticals has helped advance cancer chemotherapy in many aspects, as most of these are designated as first-in-class drugs. Here, by examining the path from discovery to development of clinically approved drugs of marine origin for cancer treatment-cytarabine (Cytosar-U®), trabectedin (Yondelis®), eribulin (Halaven®), brentuximab vedotin (Adcetris®), and plitidepsin (Aplidin®)-together with those in late clinical trial phases-lurbinectedin, plinabulin, marizomib, and plocabulin-the present review offers a critical analysis of the contributions given by these new compounds to cancer pharmacotherapy. 1 | INTRODUCTION Natural products have long been used in the treatment of human maladies and set a strong foundation upon which modern pharmacology has been erected. Particularly for cancer treatment, chemotherapeutic agents of natural origin have remarkably impacted the field, not only for their clinical importance but also for allowing the expansion of knowledge in cancer pharmacology. Natural agents like doxorubicin, paclitaxel, vincristine, and vinblastine are commonly used as first-line treatments for several cancers. The compounds of marine origin have a more recent history. Nevertheless, studies have shown their unique

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“…Brentuximab vedotin (BV) is a chimeric IgG1 anti-CD30 antibody–drug conjugated by a protease-cleavable linker to the microtubule-disrupting agent monomethyl auristatin E that has shown impressive antitumor activity in both HL and ALCL. 5 Targeted delivery of monomethyl auristatin E to CD30 expressing tumor cells is the primary mechanism of action of BV. Additional mechanisms of tumor cell death that may contribute to the clinical activity of this drug include antibody-dependent cellular phagocytosis, immunogenic cell death, and the bystander effect.…”

Section: Introductionmentioning

confidence: 99%

Brentuximab vedotin in Hodgkin lymphoma and anaplastic large-cell lymphoma: an evidence-based review

Donato¹,

Fernández-Zarzoso²,

Hueso³

et al. 2018

OTT

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Hodgkin lymphoma (HL) and anaplastic large-cell lymphoma (ALCL) account for ~10% and 2%–3% of all cases of lymphoid neoplasms, respectively. Up to 30% of patients with HL are refractory or relapse after first-line therapy, and elderly patients with HL represent a subgroup of patients with suboptimal responses to the currently available treatments. Five-year overall survival for ALCL patients is 50%–80% with conventional chemotherapy. Therefore, new therapeutic approaches are needed for these groups of patients. Brentuximab vedotin is a chimeric IgG1 anti-CD30 antibody–drug conjugate that has all the features that are necessary to make a substantive difference with the standard therapies in patients with HL and ALCL: a novel mechanism of action, single-agent activity, non-cross-resistance, and safety both in the relapsed-refractory and in the front-line setting. This review provides an update of the results of the most relevant clinical trials including brentuximab vedotin for patients with HL and ALCL conducted to date.

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Brentuximab vedotin: clinical updates and practical guidance

Cited by 45 publications

References 95 publications

Antibody–Drug Conjugates: Future Directions in Clinical and Translational Strategies to Improve the Therapeutic Index

Antibody–Drug Conjugates: Future Directions in Clinical and Translational Strategies to Improve the Therapeutic Index

Enriching cancer pharmacology with drugs of marine origin

Brentuximab vedotin in Hodgkin lymphoma and anaplastic large-cell lymphoma: an evidence-based review

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