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    DRUG:

    ladiratuzumab vedotin (SGN-LIV1A)

    i
    Other names: SGN-LIV1A, Anti-LIV-1 ADC, MK-6440
    Company:
    Merck (MSD), Pfizer
    Drug class:
    Microtubule inhibitor, LIV-1-targeted antibody-drug conjugate
    Related drugs:
    6d
    Morpheus-TNBC: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer (clinicaltrials.gov)
    P1/2, N=792, Recruiting, Hoffmann-La Roche | N=580 --> 792 | Trial completion date: May 2028 --> Sep 2030 | Trial primary completion date: May 2028 --> Sep 2030
    Enrollment change • Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    PD-L1 expression • PIK3CA mutation
    |
    VENTANA PD-L1 (SP142) Assay
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • Ibrance (palbociclib) • carboplatin • gemcitabine • Enhertu (fam-trastuzumab deruxtecan-nxki) • capecitabine • Verzenio (abemaciclib) • albumin-bound paclitaxel • Kisqali (ribociclib) • fulvestrant • Halaven (eribulin mesylate) • letrozole • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Itovebi (inavolisib) • Actemra IV (tocilizumab) • atirmociclib (PF-07220060) • ladiratuzumab vedotin (SGN-LIV1A) • selicrelumab (RG7876)
    2ms
    SDP-LIV1, a Novel and Optimized LIV-1 Antibody-drug Conjugate Demonstrating Superior Anti-Tumor Efficacy and Favorable Safety Profile for Treatment of Solid Tumors. (PubMed, Mol Cancer Ther)
    Ladiratuzumab vedotin (SGN-LIV1A), a LIV-1 targeting ADC with payload of monomethyl auristatin E, has been discontinued from clinical development...Here, we demonstrated a novel LIV-1 directed ADC, SDP-LIV1, consisting of an in-house developed anti-LIV-1 antibody conjugated to a proprietary topoisomerase I inhibitor via a cleavable GGFG (glycine-glycine-phenylalanine-glycine) linker, with an optimized average drug-to-antibody ratio of 6. Preclinical studies revealed that SDP-LIV1 showed promising in vitro and in vivo efficacy in breast and gastric cancers with favorable preclinical pharmacokinetics and safety profiles, suggesting that SDP-LIV1 has great potential for the clinical treatment of patients with solid tumor expressing LIV-1.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HR positive • HER-2 negative • EGFR positive
    |
    ladiratuzumab vedotin (SGN-LIV1A)
    4ms
    Antibody-drug conjugates in breast cancer: From therapeutic and immune activation mechanisms to resistance prevention. (PubMed, Int Rev Immunol)
    The FDA-approved ADCs include trastuzumab emtansine (T-DM1), sacituzumab govitecan (SG-Trop2), and trastuzumab deruxtecan (T-DXd), as well as two emerging ADCs, i.e. datopotamab deruxtecan (Dato-DXd) and ladiratuzumab vedotin (LV). Strategies to mitigate ADCs resistance include multi-target ADCs, and stability-enhancing linkers that also reduce off-target toxicities. ADCs continue to play key roles in breast cancer treatment, while next-generation ADCs may address current ADCs' limitations and resistance mechanisms.
    Review • Journal • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Trodelvy (sacituzumab govitecan-hziy) • Datroway (datopotamab deruxtecan-dlnk) • ladiratuzumab vedotin (SGN-LIV1A)
    12ms
    KEYNOTE 721: Safety and Efficacy of SGN-LIV1A Plus Pembrolizumab for Patients With Locally-Advanced or Metastatic Triple-Negative Breast Cancer (clinicaltrials.gov)
    P1/2, N=186, Completed, Seagen Inc. | Active, not recruiting --> Completed | Trial completion date: Jan 2026 --> Sep 2024 | Trial primary completion date: Jan 2026 --> Sep 2024
    Trial completion • Trial completion date • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)
    |
    HER-2 expression
    |
    Keytruda (pembrolizumab) • ladiratuzumab vedotin (SGN-LIV1A)
    over1year
    Morpheus-TNBC: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer (clinicaltrials.gov)
    P1/2 | N=580 | Recruiting | Sponsor: Hoffmann-La Roche | N=242 ➔ 580 | Trial completion date: May 2026 ➔ May 2028 | Trial primary completion date: May 2026 ➔ May 2028
    Enrollment change • Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • gemcitabine • Enhertu (fam-trastuzumab deruxtecan-nxki) • capecitabine • Verzenio (abemaciclib) • albumin-bound paclitaxel • Kisqali (ribociclib) • fulvestrant • Halaven (eribulin mesylate) • letrozole • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Itovebi (inavolisib) • Actemra IV (tocilizumab) • ladiratuzumab vedotin (SGN-LIV1A) • selicrelumab (RG7876)
    over1year
    KEYNOTE 721: Safety and Efficacy of SGN-LIV1A Plus Pembrolizumab for Patients With Locally-Advanced or Metastatic Triple-Negative Breast Cancer (clinicaltrials.gov)
    P1/2, N=186, Active, not recruiting, Seagen Inc. | Trial completion date: Dec 2024 --> Jan 2026 | Trial primary completion date: Mar 2024 --> Jan 2026
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)
    |
    Keytruda (pembrolizumab) • ladiratuzumab vedotin (SGN-LIV1A)
    over1year
    Expanded Access Use of Ladiratuzumab Vedotin in Advanced Solid Tumors (clinicaltrials.gov)
    P=N/A, N=0, Available, Seagen Inc.
    New trial • Metastases
    |
    ladiratuzumab vedotin (SGN-LIV1A)
    almost2years
    Expression of cell surface zinc transporter LIV1 in triple negative breast cancer is an indicator of poor prognosis and therapy failure. (PubMed, J Cell Physiol)
    Recently, in the United States of America, FDA approved the use of a new drug targeting LIV1, antibody drug conjugate SGN-LIV1A for treatment of TNBC patients...Finally, TNBC patients with 3+ staining intensity showed poor survival (4.44 year) as compared to patients with 2+ LIV1 expression (5.47 year), emphasizing that LIV1 expression is a poor prognostic factor in TNBC. In conclusion, the study reports elevated expression of LIV1 in a large Indian TNBC cohort; high expression is a poor prognostic factor and correlated with aggressive disease and indicating the need for LIV1 targeted therapies.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
    |
    CD8 expression
    |
    ladiratuzumab vedotin (SGN-LIV1A)
    almost2years
    SGNLVA-005: A Study of Ladiratuzumab Vedotin in Advanced Solid Tumors (clinicaltrials.gov)
    P2, N=205, Terminated, Seagen Inc. | Trial completion date: Jul 2025 --> Nov 2023 | Active, not recruiting --> Terminated | Trial primary completion date: May 2024 --> Nov 2023; Study closed due to portfolio prioritization
    Trial completion date • Trial termination • Trial primary completion date • Metastases
    |
    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • BRCA (Breast cancer early onset)
    |
    HER-2 overexpression • BRAF mutation • BRCA mutation
    |
    Keytruda (pembrolizumab) • ladiratuzumab vedotin (SGN-LIV1A)
    almost2years
    KEYNOTE 721: Safety and Efficacy of SGN-LIV1A Plus Pembrolizumab for Patients With Locally-Advanced or Metastatic Triple-Negative Breast Cancer (clinicaltrials.gov)
    P1/2, N=186, Active, not recruiting, Seagen Inc. | Phase classification: P1b/2 --> P1/2
    Phase classification • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)
    |
    HER-2 expression • PGR expression
    |
    Keytruda (pembrolizumab) • ladiratuzumab vedotin (SGN-LIV1A)
    2years
    Morpheus-TNBC: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer (clinicaltrials.gov)
    P1/2; Active, not recruiting --> Recruiting
    Enrollment open • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    PD-L1 expression • PIK3CA mutation
    |
    VENTANA PD-L1 (SP142) Assay
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • gemcitabine • Enhertu (fam-trastuzumab deruxtecan-nxki) • capecitabine • Verzenio (abemaciclib) • albumin-bound paclitaxel • Kisqali (ribociclib) • fulvestrant • Halaven (eribulin mesylate) • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Itovebi (inavolisib) • Actemra IV (tocilizumab) • ladiratuzumab vedotin (SGN-LIV1A) • selicrelumab (RG7876)
    over2years
    KEYNOTE 721: Safety and Efficacy of SGN-LIV1A Plus Pembrolizumab for Patients With Locally-Advanced or Metastatic Triple-Negative Breast Cancer (clinicaltrials.gov)
    P1b/2, N=186, Active, not recruiting, Seagen Inc. | Recruiting --> Active, not recruiting
    Enrollment closed • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)
    |
    HER-2 expression • PGR expression
    |
    Keytruda (pembrolizumab) • ladiratuzumab vedotin (SGN-LIV1A)