ladiratuzumab vedotin (SGN-LIV1A) / Merck (MSD), Pfizer - LARVOL DELTA

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 | Sponsor: Hoffmann-La Roche | N=56 ➔ 792

Enrollment change • Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PD-L1

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=1132 | Recruiting | Sponsor: Hoffmann-La Roche | N=792 ➔ 1132

Enrollment change • Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PD-L1

Preclinical characterization of novel LIV1 antibody drug conjugates (AACR 2026) - "After conjugation into ADCs, the T1/2 of 48D6 ADC-2 ranged 10.4~11.6 days while that of SGN-LIV1A analog in mice is 3.7~3.9 days. LIV1 targeting ADC-2 and ADC-3 exhibited strong anti-tumor activities as monotherapy in PDX models and the anti-tumor activity is further enhanced by checkpoint inhibitor. ADC-2 displayed excellent tolerability profile in mice. These results support further investigation of our LIV1 ADCs in LIV1 positive solid tumors."

ADC • IO biomarker • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • PD-L1

Preclinical development of SCR-A003, a novel topoisomerase I inhibitor-based antibody-drug conjugate (ADC) targeting LIV-1 for solid cancer (AACR 2025) - "SCR-A003, exhibited a favorable preclinical profile, with potent in vivo activity toward LIV-1-expressing tumor xenografts representing a range of cancer indications. These data support clinical development of SCR-A003 for the treatment of LIV-1-expressing solid cancers."

ADC • Preclinical • Breast Cancer • Melanoma • Oncology • Ovarian Cancer • Solid Tumor • SLC39A6

SDP03923-000-9106, a novel and optimized LIV-1 ADC with superior anti-tumor efficacy in breast cancer xenograft models (AACR 2024) - "In summary, SDP03923-000-9106 is a novel LIV-1 targeted ADC with a highly permeable payload demonstrating great anti-tumor activity across multiple types of tumors in preclinical studies. The promising preclinical data support advancing SDP03923-000-9106 into clinical testing, and Investigational New Drug (IND) application to NMPA has been submitted."

ADC • Preclinical • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Triple Negative Breast Cancer • HER-2 • SLC39A6 • SPR

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=242 | Recruiting | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PD-L1

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 • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PD-L1

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=242 | Active, not recruiting | Sponsor: Hoffmann-La Roche | N=133 ➔ 242 | Trial completion date: May 2024 ➔ May 2026 | Trial primary completion date: May 2024 ➔ May 2026

Enrollment change • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PD-L1

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=280 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Aug 2021 ➔ Jun 2022 | Trial primary completion date: Aug 2021 ➔ Jun 2022

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • PD-L1

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=280 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Mar 2023 ➔ Sep 2023 | Trial primary completion date: Mar 2023 ➔ Sep 2023

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PD-L1

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=280 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2023 ➔ May 2024 | Trial primary completion date: Sep 2023 ➔ May 2024

Enrollment closed • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PD-L1

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=280 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jun 2022 ➔ May 2023 | Trial primary completion date: Jun 2022 ➔ May 2023

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • PD-L1

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=260 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P1/2 trial • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • PD-L1

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 | Sponsor: 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 • Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PD-L1

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=133 | Active, not recruiting | Sponsor: Hoffmann-La Roche | N=280 ➔ 133

Enrollment change • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PD-L1

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=260 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting | Initiation date: Feb 2018 ➔ Mar 2018

Enrollment open • Trial initiation date • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • PD-L1

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=280 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: May 2023 ➔ Jan 2023 | Trial primary completion date: May 2023 ➔ Jan 2023

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PD-L1

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 • Breast Cancer • Gastric Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

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."

IO biomarker • Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

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 | Sponsor: Seagen Inc. | Active, not recruiting ➔ Completed | Trial completion date: Jan 2026 ➔ Sep 2024 | Trial primary completion date: Jan 2026 ➔ Sep 2024

Metastases • Trial completion • Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

Perioperative treatment regimens and efficacy outcome measures in early-stage HR+/HER2- breast cancer: A systematic literature review of randomized controlled trials (SABCS 2024) - "Antibody drug conjugates (SGNLIV1A) were included in 1 RCT (1%)... Heterogeneity was observed in terms of patient characteristics, treatment regimens, and outcome measures among clinical trials in perioperative setting. EFS, a relevant efficacy outcome measure for perioperative interventions, was not reported as a primary endpoint in the existing literature; to date clinical trials evaluating perioperative neoadjuvant plus adjuvant regimens in HR+/HER2- BC have been limited. An emerging trend for clinical trials investigating immunotherapy-based perioperative neoadjuvant plus adjuvant interventions was observed, reflective of the unmet need for innovative therapies among patients with early-stage high-risk HR+/HER2- BC."

Clinical • IO biomarker • Review • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • HER-2

Novel Humanized LIV-1 Antibody Based ADCs Conjugated with Topoisomerase I Inhibitor Payloads Displayed Significantly Higher Anti-tumor Activities than MMAE based ADCs in TNBC Tumor Models (SABCS 2024) - "ADC-1 and ADC-2 displayed similar and specific cytotoxic activities against human LIV-1-expressing tumor cells in vitro, as compared to SGN-LIV1A analog (DAR8) or ADC-3...The enhanced anti-tumor activities of ADC-1 and ADC-2 are likely contributed by the high affinity binding of 48D6 to LIV-1 and high cytotoxicity of Topo I inhibitor in breast tumor cells. These data warrant further investigation of the lead LIV-1 targeting ADC (ADC-1 and ADC-2) as potential next-generation therapeutic agent in LIV-1 positive breast cancer and other solid tumors."

Preclinical • Breast Cancer • Oncology • Triple Negative Breast Cancer

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 | Sponsor: Seagen Inc. | Trial completion date: Dec 2024 ➔ Jan 2026 | Trial primary completion date: Mar 2024 ➔ Jan 2026

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

Expanded Access Use of Ladiratuzumab Vedotin in Advanced Solid Tumors (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: Seagen Inc.

Metastases • New trial • Oncology • Solid Tumor

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 • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD4 • CD8 • HER-2