Express treatment of HER2-positive breast cancer patients, a new generation of ADC reaches the phase 3 clinical endpoint

▎ WuXi AppTec content team editor June 8, 2021, Byondis announced that its new generation of antibody conjugate (ADC) trastuzumab duocarmazine (SYD985) has achieved progression-free survival (PFS) in the Phase 3 clinical study TULIP The main end point
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In treated patients with HER2-positive unresectable locally advanced or metastatic breast cancer, the drug achieved a statistically significant improvement in PFS compared with the treatment chosen by the doctor
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This study also obtained preliminary positive overall survival (OS) results
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The detailed results of the experiment will be published at a subsequent scientific conference
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Trastuzumab duocarmazine was granted Fast Track status for the treatment of metastatic HER2-positive breast cancer by the US FDA in January 2018
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In addition, Byondis plans to submit a Biologics License Application (BLA) to the US FDA before the end of 2021
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Trastuzumab duocarmazine is an ADC that targets HER2
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Its antibody part can target HER2 binding on the surface of cancer cells, causing ADC to be internalized by the cell
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The payload of this ADC is inactive when it is coupled to the antibody.
After the linker is hydrolyzed and cleaved, the inactive cytotoxin is activated, which induces DNA damage and leads to tumor cell death
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In addition, the uptake of activated payloads by adjacent tumor cells with lower HER2 expression may increase the therapeutic potential, the so-called bystander effect
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The drug is developed using Byondis’ proprietary duocarmazine linker drug (Linker-drug, LD) technology platform
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Although early ADCs improved targeting and cell killing effects, they were not stable in the blood circulation, leading to the premature release of cytotoxic payloads, which affected healthy tissues and narrowed the treatment window
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Through the LD platform, the cytotoxic drugs carried by the new generation ADCs will quickly self-destruct once they are released in advance, thereby limiting the damage to healthy tissues and improving the treatment window
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▲The mechanism of action of Trastuzumab duocarmazine (picture source: Byondis official website) Breast cancer is the most common cancer in the world and the leading cause of cancer deaths in women in more than 100 countries.
It is estimated that there will be 2.
3 million new cases in 2020
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Especially in developing countries, the incidence is rising, and most cases are already in the late stage when they are diagnosed
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In HER2-positive breast cancer, overexpression of HER2 protein leads to uncontrolled reproduction of breast cells.
Compared with HER2-negative patients, the disease is more aggressive, more likely to relapse, and has a worse prognosis
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About 20% of breast cancers are HER2-positive, and young women are the most affected
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The current treatments for HER2-positive breast cancer include surgery, radiotherapy, chemotherapy and targeted therapy
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Trastuzumab duocarmazine is currently being studied in multiple clinical trials
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Byondis initiated a phase 2 clinical trial and a phase 1 study in HER2-positive patients with recurrent, advanced or metastatic endometrial cancer to explore the synergistic effect of trastuzumab duocarmazine and niraparib
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Researchers are also exploring the effect of trastuzumab duocarmazine as a neoadjuvant therapy in early breast cancer with low HER2 expression
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Dr.
Jan Schellens, Chief Medical Officer of Byondis, said: “There is a considerable unmet medical need for patients with HER2-positive metastatic breast cancer, and trastuzumab duocarmazine represents a promising potential clinical development
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We are very excited about the positive top-line results of TULIP
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"Reference: [1] Byondis Announces Positive Topline Results of Pivotal Phase III TULIP® Study in Patients With HER2-Positive Unresectable Locally Advanced or Metastatic Breast Cancer.
Retrieved June 8, 2021, from https:// news-releases/byondis-announces-positive-topline-results-of-pivotal-phase-iii-tulip-study-in-patients-with-her2-positive-unresectable-locally-advanced-or-metastatic-breast-cancer- 301306890.
htmlNote: This article aims to introduce the progress of medical and health research, not a recommendation for treatment
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If you need guidance on the treatment plan, please go to a regular hospital for treatment
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