328TiP Phase III study of trastuzumab deruxtecan (T-DXd) with or without pertuzumab vs a taxane, trastuzumab and pertuzumab in first-line (1L), human epidermal growth factor receptor 2–positive (HER2+) metastatic breast cancer (mBC): DESTINY-Breast09

Tolaney, Sara M.; Barroso‐Sousa, Romualdo; Jiang, Ze; Park, Y.H.; Rimawi, Mothaffar F.; Manich, C. Saura; Schneeweiß, Andreas; Toi, Masakazu; Yu, Tinghui; Shetty, Jagdish; Herbolsheimer, Pia; Loibl, Sibylle

doi:10.1016/j.annonc.2021.08.611

Cited by 13 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, another head-to-head study (DESTINY-Breast09) was carrying out for the comparison between DS-8201 and trastuzumab. 211 The efficacy and safety of DS-8201 in patients with metastatic NSCLC with HER2 mutations were also assessed in DESTINY-Lung01 study. 212 Among 91 enrolled patients, 55% had a confirmed OR at a median follow-up duration of 13.1 months.…”

Section: Solid Tumorsmentioning

confidence: 99%

Antibody drug conjugate: the “biological missile” for targeted cancer therapy

Han

et al. 2022

Sig Transduct Target Ther

572

488

View full text Add to dashboard Cite

Antibody–drug conjugate (ADC) is typically composed of a monoclonal antibody (mAbs) covalently attached to a cytotoxic drug via a chemical linker. It combines both the advantages of highly specific targeting ability and highly potent killing effect to achieve accurate and efficient elimination of cancer cells, which has become one of the hotspots for the research and development of anticancer drugs. Since the first ADC, Mylotarg® (gemtuzumab ozogamicin), was approved in 2000 by the US Food and Drug Administration (FDA), there have been 14 ADCs received market approval so far worldwide. Moreover, over 100 ADC candidates have been investigated in clinical stages at present. This kind of new anti-cancer drugs, known as “biological missiles”, is leading a new era of targeted cancer therapy. Herein, we conducted a review of the history and general mechanism of action of ADCs, and then briefly discussed the molecular aspects of key components of ADCs and the mechanisms by which these key factors influence the activities of ADCs. Moreover, we also reviewed the approved ADCs and other promising candidates in phase-3 clinical trials and discuss the current challenges and future perspectives for the development of next generations, which provide insights for the research and development of novel cancer therapeutics using ADCs.

show abstract

Section: Solid Tumorsmentioning

confidence: 99%

Antibody drug conjugate: the “biological missile” for targeted cancer therapy

Han

et al. 2022

Sig Transduct Target Ther

572

488

View full text Add to dashboard Cite

show abstract

“…The DESTINY--Breast09 study, which enrolled patients with advanced HER2-positive previously untreated breast cancer, is currently ongoing. The results of this study may be very interesting, especially considering safety profile and tolerability, with expected extraordinary effectiveness [20].…”

Section: Trastuzumab Deruxtecanmentioning

confidence: 87%

Trastuzumab deruxtecan in the treatment of adult patients with HER2-positive breast cancer

Kufel-Grabowska

2023

Oncol Clin Pract

View full text Add to dashboard Cite

In 2020, approximately 18,000 women in Poland were diagnosed with breast cancer, and 6,000 of them died. In recent years, we have witnessed significant progress in the diagnosis and treatment of breast cancer patients. When detected early and treated appropriately, the prognosis is very good, and even some patients with distant metastases have experienced long-term survival. The most common biological subtype is hormone receptor-positive breast cancer, accounting for about 70% of diagnoses, showing expression of estrogen and progesterone receptors. Triple-negative breast cancer and HER2-positive breast cancer each make up approximately 15% of all cases.In the treatment of advanced HER2-positive breast cancer, a combination of docetaxel with pertuzumab and trastuzumab is used in the first line. In subsequent lines of treatment, options include trastuzumab deruxtecan (T-DXd), trastuzumab emtansine, lapatinib, tucatinib, margetuximab, and trastuzumab.Trastuzumab derukstekan is an immunoconjugate that, upon entering the cell, releases a cytostatic agent that destroys its genetic material and neighboring cells (the "bystander effect"). It significantly prolongs the time to disease progression and overall survival compared to standard treatments used in the second and subsequent lines of treatment. It represents an effective and valuable therapeutic option for patients with early-stage HER2positive metastatic breast cancer.

show abstract

“…Because BT474 trastuzumab-resistant cancer cells express HER2, we used the anti-HER2 mAb Per in combination with T-DXd as the click approach. Additionally, prior research has shown that T-DXd plus Per is superior to T-DXd alone in treating HER2-expressing tumors (NCT04784715) and others have shown T-DXd efficacy in tumors resistant to trastuzumab ( 43, 46 ). Mice inoculated with trastuzumab-resistant BT474 tumors were treated with T-DXd alone and stratified as responder or non-responders based on their tumor volume ( Fig.…”

Section: Resultsmentioning

confidence: 99%

In Vivo Biorthogonal Antibody Click for Dual Targeting and Augmented Efficacy in Cancer Treatment

Panikar,

Berry,

Shmuel

et al. 2023

Preprint

View full text Add to dashboard Cite

Antibody-drug conjugates (ADCs) have emerged as promising therapeutics for cancer treatment; however, their effectiveness has been limited by single antigen targeting, potentially leading to resistance mechanisms triggered by tumor compensatory pathways or reduced expression of the target protein. Here, we present antibody-ADC click, an approach that harnesses bioorthogonal click chemistry for in vivo dual targeting of ADCs, irrespective of the tumor's expression of the ADC-targeting antigen. We conjugated the bioorthogonal click moieties tetrazine (Tz) and trans-cyclooctene (TCO) to both antibodies and ADCs. Through in vivo clicking of antibody-TCO with antibody-Tz, we achieved sequential dual-receptor targeting in tumors. We show that the clicked antibody therapy outperformed conventional ADC monotherapy in preclinical models mimicking ADC-eligible, ADC-resistant, and ADC-ineligible tumors. Antibody-ADC click allows reversal of drug resistance through multi-antigen targeting and enhanced ADC accumulation within tumors. Antibody-ADC click enables in vivo multi-targeting without extensive bioengineering, sustains tumor treatment, and enhances antibody-mediated cytotoxicity.

show abstract

328TiP Phase III study of trastuzumab deruxtecan (T-DXd) with or without pertuzumab vs a taxane, trastuzumab and pertuzumab in first-line (1L), human epidermal growth factor receptor 2–positive (HER2+) metastatic breast cancer (mBC): DESTINY-Breast09

Cited by 13 publications

References 0 publications

Antibody drug conjugate: the “biological missile” for targeted cancer therapy

Antibody drug conjugate: the “biological missile” for targeted cancer therapy

Trastuzumab deruxtecan in the treatment of adult patients with HER2-positive breast cancer

In Vivo Biorthogonal Antibody Click for Dual Targeting and Augmented Efficacy in Cancer Treatment

Contact Info

Product

Resources

About