Clinical Progress of Antibody-Drug Conjugates

 

抗体薬物複合体の臨床開発の進展

Antibody-drug conjugates (ADCs) continue to emerge as a strong and promising strategy for target cancer therapy. Today, there are four ADCs approved and commercially available in the US, with another 175 investigational ADCs in development, from early discovery to clinical phase III trials, across both hematologic malignancies and solid tumor indications. Some of these trials are single-agent trials, while others are combinations. Companies are leveraging on lessons learned from first and second-generation trials to inform on next-generation ADC designs.

In this second installment of our 2-part ADC program, PEGS Boston’s 9th Annual Clinical Progress of Antibody-Drug Conjugates will invite investigators to share their latest results from preclinical and clinical trials, lessons learned to inform drug design & dosing, and strategies to improve safety, efficacy and patient outcomes.

Final Agenda

THURSDAY, APRIL 11

12:00 pm Registration

12:35 Luncheon in the Exhibit Hall with Poster Viewing

薬剤設計と投薬に必要な情報を提供し、患者の予後を改善するための戦略

1:40 Chairperson’s Opening Remarks

Gregory P. Adams, PhD, CSO, Sesen Bio

1:50 Single-Cell PK/PD of Antibody-Drug Conjugates and Immuno-Oncology Agents to Design More Effective Therapies

Thurber_GregGreg Thurber, PhD, Assistant Professor, Chemical Engineering and Biomedical Engineering, University of Michigan

Antibody-drug conjugates and checkpoint inhibitors are powerful agents in the treatment of cancer. However, the delivery and distribution of these agents in the tumor microenvironment is complex. We are using single-cell measurements within the tumor to inform better decisions on drug design and dosing.

2:20 Strategies for Dosing Schedule to Maximize Therapeutic Index of ADCs

Mary Jane Hinrichs, PhD, Associate Director, Clinical Scientist, MedImmune

2:50 Developing Antibody-Drug Conjugates as Targeted Conditioning Agents for Bone Marrow Transplant

McDonagh_CharlotteCharlotte McDonagh, PhD, Vice President, Head, Biotherapeutics, Magenta Therapeutics

Many diseases can be cured by a bone marrow transplant. Prior to transplant, patients are conditioned by removing their own bone marrow stem cells using toxic, non-selective chemotherapy and radiation. Many patients suffer serious side effects, and others refuse a transplant. This presentation will highlight preclinical development of antibody-drug conjugates that may be safer, targeted agents for patient preparation with the aim of extending the use of curative bone marrow transplant and improving patient outcomes.

3:20 Sponsored Presentation (Opportunity Available)

3:50 Networking Refreshment Break

抗体薬物複合体の安全性と有効性の向上

4:20 Preclinical Study of Liver Injury Induced by T-DM1: Molecular Mechanisms of T-DM1-Induced Hepatotoxicity

Wu_WenJinWen Jin Wu, MD, PhD, Senior Investigator, OBP, CDER, FDA

Hepatotoxicity is one of the serious adverse events associated with T-DM1. We show that T-DM1 is internalized upon binding to cell surface HER2, resulting in DM1-associated cytotoxicity, including disorganized microtubules, nuclear fragmentation/multiple nuclei, and cell growth inhibition. Based on our data, we propose that T-DM1-induced upregulation of TNFa enhances the liver injury that may be initially caused by DM1-mediated intracellular damage. In addition, a novel target that mediates T-DM1-induced hepatotoxicity will also be discussed.

4:50 Improving the Efficacy and Safety Profile of a Recombinant Immunotoxin by Mitigating Immunogenicity with Tolerogenic Nanoparticles

Kishimoto_KeiKei Kishimoto, PhD, CSO, Selecta Biosciences

We have developed tolerogenic nanoparticles encapsulating rapamycin (SVP-Rapamycin) that have been shown the ability to inhibit the formation of anti-drug antibodies against an immunogenic enzyme therapy for severe, chronic gout in humans. In collaboration with the NCI, preclinical studies have demonstrated SVP-Rapamycin inhibits the formation of anti-drug antibodies to LMB-100, a mesothelin-directed immunotoxin. The safety and tolerability of SEL-402, a combination of LMB-100 co-administered with SVP-Rapamycin, is currently being evaluated for the treatment of mesothelioma in a Phase I clinical trial.

5:20 End of Day

5:20 Registration for Dinner Short Courses


Recommended Dinner Short Course*

SC12: Design Strategies and Development of ADCs

Robert Lutz, PhD, Principal Consultant, Crescendo Biopharma Consulting

 

*Separate registration required.

FRIDAY, APRIL 12

8:00 am Morning Coffee

8:30 Chairperson’s Remarks

Greg Thurber, PhD, Assistant Professor, Chemical Engineering and Biomedical Engineering, University of Michigan


8:35 KEYNOTE PRESENTATION: The House of Vedotins

Lechleider_RobertRobert J. Lechleider, MD, Senior Vice President, Clinical Development, Seattle Genetics

Antibody-drug conjugates have proven effective in treating an array of cancers. Among the most active drug-linker combinations is monomethyl-auristatin E (MMAE) coupled to a targeting antibody via a valine-citrulline linker. MMAE conjugates have shown activity in heme and solid tumors using a number of targeting antibodies. The role and future of MMAE drug conjugates in the treatment of cancer will be discussed.

前臨床研究の最新情報とコンセプトの実証

9:05 A Novel Antibody-Drug Conjugate Targeting ADAM9-Expressing Solid Tumors Demonstrates Potent Preclinical Activity

Hicks_StuartStuart Hicks, PhD, Associate Director, Pipeline R&D, ImmunoGen


9:35 CD163 as a Target for Directing ADCs to Macrophages in Cancer and Inflammation – Preclinical Proof of Concept

Graversen_JonasJonas Heilskov Graversen, PhD, Associate Professor, Molecular Medicine, University of Southern Denmark

We have validated the macrophage specific internalization receptor CD163 as an ADC target in cancer and inflammation. PoC studies in mice, rats and pigs show a strongly reduced (50-fold) effective dose for anti-inflammatory effect when targeting dexamethasone to macrophages (endotoxemia and NASH models). In cancer we observe substantially increased infiltration of effector T-cells and T-cell dependent tumor regression in a murine anti-PD-1 resistant melanoma model when eradicating tumor associated macrophages by toxin targeting.

10:05 Networking Coffee Break

臨床開発と教訓

10:35 Overcoming Brentuximab Resistance with MDR1 Inhibitors

Chen_RobertRobert Chen, MD, Associate Professor, Hematology & Hematopietic Cell Transplantation, City of Hope National Medical Center


11:05 Targeting Breast Cancer with Antibody-Drug Conjugates

Bardia_AdityaAditya Bardia, MD, MPH, Assistant Professor, Medicine, Harvard Medical School

Chemotherapy is the mainstay of management of multiple solid tumors, but can be associated with considerable adverse effects. Conceptually, antibody-drug conjugates can be utilized for targeted delivery of toxic payloads to cancer cells. However, antigen selection of antigen and tumor heterogeneity are significant challenges in clinical development of novel antibody-drug conjugates. In this presentation, we will review potential therapeutic strategies and the clinical development of antibody-drug conjugates in breast cancer.

11:35 Discovery of Next-Generation ADCs: Preclinical and Clinical Development of AVID100, an EGFR-Targeting ADC

O'Connor-McCourt_MaureenMaureen O’Connor-McCourt, PhD, CSO, Forbius

AVID100 is an EGFR-targeting ADC which was designed by screening a library of anti-EGFR ADCs against both tumor and normal cells expressing EGFR. This approach enabled us to identify AVID100, which exhibited a very promising therapeutic index in preclinical studies. AVID100 recently completed a successful phase 1 clinical program and a phase 2 study has been initiated. Importantly, only modest skin toxicity was observed, as predicted by our preclinical data.

12:05 pm [Fam-] Trastuzumab Deruxtecan (DS 8201) Clinical Development Update

Held_ThomasThomas Held, MBA, Vice President, ADC Task Force, Daiichi Sankyo


12:35 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:05 Networking Refreshment Break

1:35 Chairperson’s Remarks

Mary Jane Hinrichs, PhD, Associate Director, Clinical Scientist, MedImmune

1:40 Development and Clinical Updates on Sacituzumab Govitecan

Robert Iannone, MD, MSCE, Head, R&D, CMO, Immunomedics

2:10 The Right Agent for the Right Space - Clinical Development of an Anti-Epcam/Toxin Fusion Protein for the Treatment of Non-Muscle Invasive Bladder Cancer

Adams_GregGregory P. Adams, PhD, CSO, Sesen Bio

Bladder cancer is most effectively treated before the disease has reached the muscle layer surrounding the bladder. Once first line treatment fails it is recommended that patients have their bladder removed to prevent systemic disease. Vicinium is a potent fusion protein currently in a Phase III trial that targets against EpCAM, a tumor-associated antigen which is significantly over expressed in high grade bladder cancer and minimally present in healthy bladder tissue, potentially making it an ideal agent for local-regional treatment. Vicinium’s preclinical and clinical development will be discussed.

2:40 Targeting CD74 with a Novel Antibody-Drug Conjugate, STRO-001 for Treatment of B-Cell Malignancies

Molina_ArturoArturo Molina, MD, MS, FACP, CMO, Sutro Biopharma


3:10 Tisotumab Vedotin – A Novel Tissue Factor-Targeting Antibody-Drug Conjugate for the Treatment of Advanced Solid Tumors

Harris_JeffreyJeffrey Harris, PhD, Associate Director, Translational Research, Genmab

Tisotumab vedotin (TV) is an antibody-drug conjugate (ADC) that binds and interferes with tissue factor signaling, has potent anti-tumor activity in vitro and in vivo, and minimal effect on pro-coagulant activity. TV is efficiently internalized to the lysosome of the cell, making it an optimal ADC. TV is currently being tested in multiple clinical trials evaluating the safety, tolerability, and anti-tumor activity in patients with previously treated and advanced metastatic solid tumors.

3:40 End of Conference

* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。

Choose your language
Traditional Chinese
Simplified Chinese
Korean
English


更新通知サービス
更新履歴
2019/02/15
スポンサー更新
2019/02/05
アジェンダ・講演者・スポンサー更新
2019/01/09
スポンサー更新


Premier Sponsors


表示切替:



メール配信サービス