The Antibody Society

the official website of the antibody society

An international non-profit supporting antibody-related research and development.

  • LOG IN
  • BECOME A MEMBER
  • About
    • Mission & Activities
    • Board of Directors
    • Our Staff & Volunteers
    • The Antibody Society’s Standing Committees
      • AIRR Community Committee
      • Communication & Membership Committee
      • Executive Committee
      • Finance & Audit Committee
      • Governance & Nominating Committee
      • Initiatives Committee
      • Meetings Committee
    • Sponsors & Partners
  • Society meetings
    • Biopharmaceutical Informatics Symposium
    • Harnessing Cytokines for Cancer Immunotherapy Symposium
    • Emerging Cancer Therapies Leveraging Gamma-Delta Effector T cells Symposium
    • Emerging Immunotherapeutics for Ovarian Cancer Symposium
    • AIRR Community Meetings
    • Antibody Engineering & Therapeutics (US) 2022
      • 2020 Antibody Engineering & Therapeutics
      • 2019 Antibody Engineering & Therapeutics
      • 2018 Antibody Engineering & Therapeutics
      • What is INN a Name?
        • INN issue updates
    • Antibody Engineering & Therapeutics Europe 2022
    • FOCIS Symposia
  • AIRR Community
    • AIRR News
    • AIRR Publications
    • AIRR Meetings
      • AIRR Community Meeting VI: “Exploring New Frontiers”
      • AIRR Community Meeting V: “Zooming in to the AIRR Community”
      • AIRR Community Meeting V Pre-Meetings
        • AIRR-seq in the Pandemic
        • AIRR-seq Biological Standards and Workflows
      • AIRR Community Special Event: “Response to COVID-19”
      • AIRR Community Meeting IV: “Bridging the Gaps”
      • AIRR Community Meeting III
        • Day 1
        • Day 2
        • Day 3
        • Day 4
      • AIRR Community Meeting II
      • AIRR Community Meeting I
    • AIRR Community Working Groups
      • Biological Resources Working Group
      • Common Repository Working Group
      • Diagnostics Working Group
      • Germline Database Working Group
      • Legal and Ethics Working Group
      • Software Working Group
      • Standards Working Group
    • AIRR Community Sub-committees
      • Communications Sub-committee
      • Executive Sub-committee
      • Inferred Allele Review Committee
      • Meetings Sub-committee
    • AIRR Data Commons
    • AIRR Community Calendar
    • AIRR Community Webinar Series
    • On AIRR – An AIRR Community Podcast
    • AIRR Community Resources
    • AIRR Community Service Prize 2022
  • Members only
    • Login
    • Note to members
    • James S. Huston Antibody Science Talent Award
      • 2020 James S. Huston Antibody Science Talent Award Recipient
      • JSH Award Criteria
    • Research Competitions
    • Science Writing Competition
      • Science Writing Competition Winners
    • Discount codes for meeting registration
    • Antibodies in early-stage studies
    • Presentations
  • Upcoming meetings
  • Web Resources
    • Society Publications
    • Antibody News
    • Antibody therapeutics approved or in regulatory review in the EU or US
      • Antibody therapeutics product data
    • Antibodies in late-stage clinical studies
    • Research Resources
    • Education Resources
  • Career Center
    • Career Shorts
  • Learning Center
    • Upcoming Webinars
    • Adaptive Immune Receptor Repertoires
    • Antibody Discovery & Development
    • Commercializing Antibody Therapeutics
    • Antibodies to Watch
    • Antibody Validation
  • COVID-19
    • Guide to “Coronavirus in the Crosshairs”
    • COVID-19 Biologics Tracker
    • Meeting Report: The Diagnostic Landscape for COVID-19
You are here: Home / ADC / Antibody-drug conjugates in the spotlight

Antibody-drug conjugates in the spotlight

October 14, 2016 by Janice Reichert

square logo ADCAntibody-drug conjugates (ADCs) are designed to deliver cytotoxic agents into targeted cells, and they are typically developed as treatments for cancer. Due to the need for new cancer drugs, the development of ADCs is the focus of substantial efforts by the biopharmaceutical industry. Nearly 60 ADCs are currently in clinical studies, one ADC, inotuzumab ozogamicin, is undergoing regulatory review, and three ADCs have been granted approvals, although the first to be approved, gemtuzumab ozogamicin (Mylotarg®) was withdrawn from the market in 2010.

Two ADCs, brentuximab vedotin (Adcetris®) and ado-trastuzumab emtansine (Kadcyla®), are currently marketed in the United States (US) and European Union (EU), as well as other countries. These two ADCs are disparate in their composition, and are used as treatments for different indications. Brentuximab vedotin is composed of an anti-CD30 monoclonal antibody (mAb) conjugated to the tubulin inhibitor monomethyl auristatin E via a valine-citruline dipeptide linkage designed for conditional cleavage inside cells. In contrast, ado-trastuzimab emtansine comprises an anti-human epidermal growth factor receptor-2 (HER2) mAb coupled to the tubulin-disrupting maytansinoid DM1 drug via a non-reducible thioether linkage. Brentuximab vedotin was granted its first approval in 2011 for two indications: 1) classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplantation or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates; and 2) systemic anaplastic large cell lymphoma after failure of at least one prior multi-agent chemotherapy regimen. The first approval for ado-trastuzumab emtansine was granted in 2013; the product is indicated for the treatment of HER2-positive metastatic breast cancer in patients who previously received trastuzumab and a taxane separately or in combination.

Of the nearly 60 ADCs in the clinic, only two (depatuxizumab mafodotin, vadastuximab talirane) are currently in late-stage (Phase 2/3 or 3) clinical studies, but two additional ADCs (sacituzumab govitecan, mirvetuximab soravtansine) may transition to Phase 3 soon. Depatuxizumab mafodotin (ABT-414) is composed of an anti-epidermal growth factor receptor (EGFR) mAb conjugated to the tubulin inhibitor monomethyl auristatin F via a stable maleimidocaproyl linker. The Phase 2b/3 Intellance 1 study (NCT02573324) of the ADC with concurrent chemoradiation and adjuvant temozolomide in adult patients with newly diagnosed glioblastoma multiforme (GBM) with EGFR amplification was initiated in late 2015. Depatuxizumab mafodotin has orphan drug designations for GBM in the US and glioma in the EU, and it was granted a US Rare Pediatric Disease Designation for pediatric EGFR-amplified diffuse intrinsic pontine glioma, a brainstem tumor that is highly aggressive and difficult to treat. Vadastuximab talirane (SGN-33A) is an anti-CD33 mAb with 2 engineered cysteine residues through which DNA cross-linking pyrrolobenzodiazepine dimer drug moieties are conjugated via a protease-cleavable valine-alanine dipeptide linker. The Phase 3 CASCADE clinical trial (NCT02785900) of vadastuximab talirine in combination with azacitidine (Vidaza) or decitabine (Dacogen) in older patients with newly diagnosed acute myeloid leukemia (AML) was initiated in May 2016.  Results from a Phase 1 study indicated that the ADC in combination with hypomethylating agents was a well-tolerated regimen with a high remission rate in older patients with AML.

The transitions of sacituzumab govitecan (IMMU-132) and mirvetuximab soravtansine (IMGN853) to Phase 3 may occur by the end of 2016. The start of a Phase 3 study (NCT02574455) that will evaluate the safety and efficacy of sacituzumab govitecan in refractory/relapsed triple-negative breast cancer (TNBC) patients is scheduled for December 2016. This ADC has received US Breakthrough Therapy and Fast Track designations for the treatment of patients with TNBC. Sacituzumab govitecan comprises an anti-TROP-2 mAb conjugated via a pH-sensitive linker to SN-38, the active metabolite of the chemotherapeutic irinotecan, in a site-specific manner. Mirvetuximab soravtansine is being assessed as a single-agent therapy in the FORWARD I trial (NCT02631876) of the ADC versus investigator’s choice of chemotherapy in adults with folate receptor (FR)-α positive advanced epithelial ovarian cancer, primary peritoneal cancer or primary fallopian tube cancer, which is being changed from a Phase 2 to a Phase 3 trial. Mirvetuximab soravtansine is composed of an anti-FRα mAb linked to the tubulin-disrupting maytansinoid DM4 via a cleavable linker.

It should be noted that, despite the increased complexity of the molecules, ADCs are also the focus of companies developing biosimilar products. As discussed in previous Society posts, biosimilars of antibody-based drugs that have lost patent protection, including adalimumab (Humira®), rituximab (Rituxan®, Mabthera®), trastuzumab (Herceptin®) and etanercept (Enbrel®), are already approved or undergoing regulatory review in the US and EU, as well as other countries.

The Antibody Society thanks Hanson Wade for access to Beacon, the World ADC database.

Like this post? Please become a member!

Filed Under: ADC, Clinical pipeline, Phase 3 pipeline Tagged With: Antibody drug conjugates, antibody therapeutics

Share this post

  • LinkedIn

Career Center

Our Career Center is a premier resource to connect highly qualified talent with matching career opportunities. Visit for details on over 800 jobs!

AIRR Community

AIRR Community

The Adaptive Immune Receptor Repertoire Community is a research-driven group organizing around the use of high-throughput sequencing technologies to study antibody/B-cell and T-cell receptor repertoires.

Recent Posts

  • Thanks to all who participated in Antibody Engineering & Therapeutics Europe! June 9, 2022
  • European Commission approves Lunsumio for people with relapsed or refractory follicular lymphoma June 8, 2022
  • Join us on June 9th for our next webinar – Registration is open! May 26, 2022

Archives

Follow us online

  • Email
  • LinkedIn
  • Twitter
  • YouTube
  • Home
  • Privacy & Terms of Use
  • About
  • Board of Directors
  • Advisors
  • Sponsors & Partners
  • Mission & Activities
  • Join the Society
  • Membership Levels
  • Members only
  • Login
  • Antibody therapeutics approved or in regulatory review in the EU or US
  • Meeting reports
  • Presentations
  • Contact

©2015 - scicomvisuals