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    DRUG:

    DHES0815A

    i
    Other names: DHES0815A, DHES-0815A, RG6148
    Company:
    Roche
    Drug class:
    HER2-targeted antibody-drug conjugate, DNA replication inhibitor
    Related drugs:
    11ms
    The HER2-directed antibody-drug conjugate DHES0815A in advanced and/or metastatic breast cancer: preclinical characterization and phase 1 trial results. (PubMed, Nat Commun)
    Approved antibody-drug conjugates (ADCs) for HER2-positive breast cancer include trastuzumab emtansine and trastuzumab deruxtecan. To develop a differentiated HER2 ADC, we chose an antibody that does not compete with trastuzumab or pertuzumab for binding, conjugated to a reduced potency PBD (pyrrolobenzodiazepine) dimer payload...A dose-escalation study (ClinicalTrials.gov: NCT03451162) in patients with HER2-positive metastatic breast cancer, with the primary objective of evaluating the safety and tolerability of DHES0815A and secondary objectives of characterizing the pharmacokinetics, objective response rate, duration of response, and formation of anti-DHES0815A antibodies, is reported herein. Despite early signs of anti-tumor activity, patients at higher doses develop persistent, non-resolvable dermal, ocular, and pulmonary toxicities, which led to early termination of the phase 1 trial.
    P1 data • Preclinical • Journal • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive
    |
    Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki) • DHES0815A
    over3years
    DHES0815A, a novel antibody-drug conjugate targeting HER2/neu, is highly active against uterine serous carcinomas in vitro and in vivo. (PubMed, Gynecol Oncol)
    DHES0815A is both highly selective and toxic to USC tumors overexpressing HER2/neu both in vitro and in vivo. HER2-directed ADCs, alone or in combination with other HER2/neu targeted agents may represent a novel treatment option for patients with tumors harboring HER2/neu overexpression refractory to trastuzumab and traditional chemotherapy.
    Preclinical • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 overexpression • HER-2 amplification • HER-2 negative • HER-2-H
    |
    Herceptin (trastuzumab) • Perjeta (pertuzumab) • DHES0815A
    over3years
    Safety, Tolerability, and Pharmacokinetic (PK) Study of DHES0815A in Participants With Human Epidermal Growth Factor Receptor (HER)2-Positive Breast Cancer (clinicaltrials.gov)
    P1, N=14, Completed, Genentech, Inc. | Active, not recruiting --> Completed | Trial completion date: Apr 2022 --> Jun 2021 | Trial primary completion date: Apr 2022 --> Jun 2021
    Clinical • Trial completion • Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive
    |
    DHES0815A
    almost4years
    [VIRTUAL] In vitro and in vivo activity of DHES0815A, an antibody-drug conjugate targeting HER2/neu in uterine serous carcinoma (AACR 2021)
    DHES0815A is a novel antibody-drug-conjugate (ADC) which binds specifically to HER2 overexpressing tumors at a distinct epitope from that bound by trastuzumab and pertuzumab after which it delivers the toxic payload, PBD-MA, a DNA mono-alkylating agent. DHES0815A is both highly selective and toxic to USC tumors overexpressing HER2/neu both in vitro and in vivo. HER2-directed ADCs, alone or in combination with other HER2/neu targeted agents may represent a novel treatment option for patients with tumors harboring HER2/neu overexpression refractory to trastuzumab and traditional chemotherapy.
    Preclinical
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 overexpression • HER-2 amplification • HER-2 negative • HER-2-H
    |
    Herceptin (trastuzumab) • Perjeta (pertuzumab) • DHES0815A
    almost4years
    [VIRTUAL] In vitro and in vivo activity of DHES0815A, an antibody-drug conjugate targeting HER2/neu in uterine serous carcinoma (SGO 2021)
    No abstract available
    Preclinical
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    DHES0815A
    over4years
    Safety, Tolerability, and Pharmacokinetic (PK) Study of DHES0815A in Participants With Human Epidermal Growth Factor Receptor (HER)2-Positive Breast Cancer (clinicaltrials.gov)
    P1;Trial completion date: Apr 2020 --> Apr 2022 | Trial primary completion date: Apr 2020 --> Apr 2022
    Trial completion date • Trial primary completion date • Clinical
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive
    |
    DHES0815A
    almost5years
    Safety, Tolerability, and Pharmacokinetic (PK) Study of DHES0815A in Participants With Human Epidermal Growth Factor Receptor (HER)2-Positive Breast Cancer (clinicaltrials.gov)
    P1, N=14, Active, not recruiting, Genentech, Inc. | Trial completion date: Jan 2022 --> Apr 2020 | Trial primary completion date: Jan 2022 --> Apr 2020
    Clinical • Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive
    |
    DHES0815A
    5years
    Safety, Tolerability, and Pharmacokinetic (PK) Study of DHES0815A in Participants With Human Epidermal Growth Factor Receptor (HER)2-Positive Breast Cancer (clinicaltrials.gov)
    P1, N=14, Active, not recruiting, Genentech, Inc. | N=55 --> 14
    Clinical • Enrollment change
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive
    |
    DHES0815A
    over5years
    Safety, Tolerability, and Pharmacokinetic (PK) Study of DHES0815A in Participants With Human Epidermal Growth Factor Receptor (HER)2-Positive Breast Cancer (clinicaltrials.gov)
    P1, N=55, Active, not recruiting, Genentech, Inc. | Recruiting --> Active, not recruiting
    Clinical • Enrollment closed
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive
    |
    DHES0815A