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

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."

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

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

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 • Metastases • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1 • PIK3CA

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

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."

Preclinical • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Negative 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

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

SGNLVA-005: A Study of Ladiratuzumab Vedotin in Advanced Solid Tumors (clinicaltrials.gov) - P2 | N=205 | Terminated | Sponsor: 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

Metastases • Trial completion date • Trial primary completion date • Trial termination • Breast Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • HER2 Breast Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ALK • BRAF • BRCA

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. | Phase classification: P1b/2 ➔ P1/2

Combination therapy • Metastases • Phase classification • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

Allogeneic CAR T cells targeting Liv-1 for breast cancer (SITC 2023) - "Liv1 is being explored clinically as a target via an antibody drug conjugate (ADC: Ladiratuzumab vedotin) which has shown encouraging safety and anti tumor data. Its specific expression in breast cancer, as opposed to other tissues, reduces the risk of off-target toxicity. We have demonstrated that anti-Liv1 CAR T cells can be produced with potent in vitro and in vivo CAR T cell activity against multiple breast cancer cell lines."

CAR T-Cell Therapy • IO biomarker • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

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 • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1 • PIK3CA

Seagen, Merck put $1.6B ADC collab on the back burner citing 'emerging treatment landscape' (FierceBiotech) - "Seagen is putting a phase 2 Merck & Co.-partnered antibody-drug conjugate on the shelf for now, nearly three years after signing on to a $1.6 billion partnership for the asset..The company—which is in the process of being acquired by Pfizer—briefly noted in a second-quarter earnings filing Thursday that ladiratuzumab vedotin, or LV, is being deprioritized. Merck confirmed in an email Thursday afternoon that the company is in the process of discontinuing the program...The Seagen statement noted that the collaboration agreement signed in 2020 is still active."

Discontinued • Breast Cancer • Genito-urinary Cancer • Melanoma • Oncology • Prostate Cancer • Skin Cancer • Solid Tumor

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 | Sponsor: Seagen Inc. | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

SGNLVA-005: A Study of Ladiratuzumab Vedotin in Advanced Solid Tumors (clinicaltrials.gov) - P2 | N=205 | Active, not recruiting | Sponsor: Seagen Inc. | Recruiting ➔ Active, not recruiting | N=414 ➔ 205

Enrollment change • Enrollment closed • Metastases • Breast Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • HER2 Breast Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ALK • BRAF • BRCA

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 • Metastases • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1 • PIK3CA

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=211 | Recruiting | Sponsor: Seagen Inc. | Trial primary completion date: Apr 2023 ➔ Mar 2024

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

[VIRTUAL] Combination Immunotherapy (IT) and Chemotherapy (CT) Can Improve Pathologic Complete Responses (pCR) in Women with Triple Negative (TNBC) and HER2+ Breast Cancer (BC) but Does Not Improve Predictability for Post Therapy Magnetic Resonance Imaging (MRI) (SSO 2020) - "We analyzed 44 TNBC and HER2 NAICT pts from 4 distinct Trx protocols including: (1) 14 TNBC pts treated with intratumoral Talimogene laherparepvec (TVEC) in combination with weekly paclitaxel (T) followed by dose dense Adriamycin and Cytoxan (ddAC); (2) 13 ER+HER2+ pts treated with subcutaneous interferon gamma (IFN-) in combination with weekly T with trastuzumab and pertuzumab (HP); (3), 6 ER-HER2+ pts treated with 3 weeks of HER2 pulsed dendritic cell vaccines (DC1) followed by Taxotere, Carboplatin, and HP; and (4), 11 pts on ISPY2 trial; 8 pts randomized to Trx with pembrolizumab with weekly T followed by ddAC, 1 pt treated with SGN-LIV1A followed by ddAC, and 2 pts treated with durvalumab, and T, followed by ddAC. The addition of IT with standard CT regimens in TNBC and HER2 BC has improved pCR but reduced the predictive capacity of MRI suggesting MRI may not be accurate enough to make further surgical decisions."

Clinical • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • IFNG

[VIRTUAL] Systemic administration of ladiratuzumab vedotin alone or in combination with pembrolizumab results in significant immune activation in the tumor microenvironment in metastatic breast cancer patients (SITC 2020) - P1, P1b/2 | "The combination of LV plus pembrolizumab resulted in a more potent immune activation in the TME and a prominent influx of CD8 T cells in addition to macrophages. Together these results provide a rationale for the continued clinical investigation of LV alone or in combination with pembrolizumab."

Biomarker • Clinical • Combination therapy • IO biomarker • Tumor microenvironment • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • PD-L1

Phase 1 open-label study of ladiratuzumab vedotin in patients with first-line unresectable locally advanced or metastatic triple-negative breast cancer (SGNLVA-001, part F, trial in progress) (SABCS 2022) - P1 | "Safety, PK, and efficacy measures will be summarized using descriptive statistics. Enrollment for Part F is ongoing in the US."

Clinical • IO biomarker • P1 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

Phase 1 study of the antibody-drug conjugate SGN-LIV1A in patients with heavily pretreated triple-negative metastatic breast cancer (SABCS 2017) - P1; "LIV-1 is expressed in almost all MBC tumors. SGN-LIV1A monotherapy was generally well tolerated and showed encouraging antitumor activity in heavily pretreated TN MBC, with a PR rate of 32%, confirmed PR rate of 21%, and CBR (≥24 wks) of 36%. Response duration data continue to evolve."

Clinical • P1 data • HER2 Breast Cancer • Hormone Receptor Breast Cancer

Post-treatment biopsies show evidence of cell cycle arrest and immune cell infiltration into tumors of ladiratuzumab vedotin-treated advanced breast cancer patients (ESMO 2018) - P1, P1b/2; "These data expand upon preclinical observations that MMAE-linked ADCs can induce mitotic arrest, immunomodulation, and immunogenic cell death. These translational data strongly support further clinical investigation of LV monotherapy and LV in combination with immuno-oncology agents, e.g. checkpoint inhibitors, as in the SGNLVA-002 study (NCT03310957)."

Clinical • IO biomarker • Hormone Receptor Positive Breast Cancer • Triple Negative Breast Cancer

[VIRTUAL] Module 3: Immune Checkpoint Inhibitors and Other Novel Strategies for the Treatment of Triple-Negative Breast Cancer (TNBC) (ASCO 2021) - "Available results from the Phase III KEYNOTE-522 and IMpassion031 trials documenting the benefit of neoadjuvant pembrolizumab or atezolizumab, respectively, with chemotherapy versus chemotherapy alone for TNBC Current nonresearch role, if any, of neoadjuvant immune checkpoint inhibition for patients with TNBC Long-term efficacy and safety findings from the Phase III IMpassion130 trial evaluating atezolizumab/nab paclitaxel as first-line therapy for metastatic TNBC (mTNBC) Primary results from the Phase III IMpassion131 study of first-line paclitaxel with or without atezolizumab for mTNBC; recent FDA alert regarding efficacy and safety concerns with this combination Key efficacy and safety findings supporting the recent FDA approval of pembrolizumab in combination with chemotherapy for patients with previously untreated PD-L1-positive mTNBC (KEYNOTE-355 trial); effect of chemotherapy partner and previous chemotherapy exposure on outcomes FDA approvals of atezolizumab/nab..."

Checkpoint inhibition • IO biomarker • Breast Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • Triple Negative Breast Cancer

Phase 1b/2 study of ladiratuzumab vedotin (LV) in combination with pembrolizumab for first-line treatment of triple-negative breast cancer (SGNLVA-002, trial in progress) (SABCS 2022) - P1, P1b/2 | "Safety and efficacy endpoints will be summarized with descriptive statistics. Global enrollment is ongoing in the US, EU, and Asia."

Clinical • Combination therapy • P1/2 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer