Eligible patients require pathologically confirmed, incurable LA/MBC (subtype-specific criteria for Parts A-F), measurable disease, ECOG 0-1, and adequate organ function; exclusions encompass severe neuropathy (≥Grade 2), untreated CNS metastases, prior LV/MMAE therapy, and trastuzumab hypersensitivity (combination arm). Tumor PD-L1/CPS and LIV-1 expression are mandated for specific cohorts.

SGNLVA-001 (NCT01969643) is an ongoing, multi-part, open label study investigating the safety and efficacy of LV in patients with metastatic breast cancer (mBC). Part E evaluated LV q1w in escalation and expansion starting at LV 1.0 mg/kg q1w. Patients with first (1L) or second line (2L) endocrine therapy refractory hormone receptor-positive (HR+)/HER2-negative (HER2-) mBC or 2L mTNBC were enrolled. Tumor assessments occurred every 6 weeks per RECIST v1.1.

Eligible patients must have untreated metastatic/locally-advanced TNBC (PD-L1 CPS<10 for Part D), measurable lesions (&ge;10mm tumor/&ge;15mm lymph node), ECOG 0-1, and adequate organ function. Key exclusions: prior immuno-oncology therapy, Grade&ge;2 neuropathy, active CNS metastases (unless treated/stable for &ge;4 weeks without steroids), recent radiotherapy (<2 weeks), active autoimmune disease/interstitial lung disease, or steroid-requiring pneumonitis.

Eligible patients must have metastatic/inoperable locally advanced breast cancer (RECIST v1.1 measurable disease), ECOG 0-1, life expectancy &ge;3 months, and adequate organ function. Key exclusions: prior immune checkpoint therapies (anti-PD-1/PD-L1/CTLA-4), active/uncontrolled CNS metastases, autoimmune/immunodeficiency disorders, severe infections, significant cardiovascular disease, recent immunosuppressants, or pregnancy/breastfeeding. Tumor biopsy/biomarker testing is mandatory.

Eligible patients must have newly diagnosed invasive breast cancer (Stage II-III or T4/Nany/M0; tumor &ge;2.5cm) without prior chemo/radiation. Key requirements: ECOG 0-1, adequate organ function, MRI compatibility, and biomarker-evaluable tumor (MammaPrint High or ER-/HER2+). Exclusions: metastatic disease, severe cardiac conditions, active infections, or prior investigational drug use within 30 days. Baseline biopsies and serial imaging are mandatory.

Secondary goals include developing predictive/prognostic models using biomarkers (from blood/tissue collected at baseline, mid-treatment, and pre/post-surgery) for pCR and residual cancer burden (RCB), while also analyzing 3/5-year relapse-free and overall survival rates. Safety profiles (AEs/SAEs) and treatment response via MRI volumetric changes (at 4 timepoints) will be monitored throughout the study.

Eligible participants had measurable disease (RECIST v1.1), ECOG 0-1, and progression after prior therapy. Cohort-specific requirements: SCLC (1 prior platinum-based chemo), NSCLC (squamous/nonsquamous; EGFR/ALK/ROS wild-type; 1 prior chemo + anti-PD (L)1), HNSCC (platinum-refractory), esophageal/gastric (HER2-treated if applicable), CRPC (no prior chemo in mCRPC), and melanoma (anti-PD (L)1-refractory, BRAF-treated if mutated). Key exclusions: active CNS metastases, Grade &ge;2 neuropathy, interstitial lung disease, or concurrent malignancy within 3 years.

The primary efficacy endpoint was Objective Response Rate (ORR) per RECIST v1.1, defined as confirmed complete (disappearance of all target lesions) or partial response (≥30% decrease in lesion diameters) in Part A (up to 8.3 months follow-up) and Part B (up to 34.7 months). For prostate cancer (Cohort 7), PSA response (≥50% reduction confirmed ≥3 weeks apart) was additionally assessed per PCWG3 criteria with a maximum follow-up of 13.5 months.

Safety profiles-including treatment-emergent adverse events (TEAEs), serious AEs (≥Grade 3), and treatment-related AEs-were monitored up to 37.5 months. Secondary endpoints included Disease Control Rate (DCR: CR/PR/SD), Duration of Response (DOR), Progression-Free Survival (PFS), and Overall Survival (OS), all evaluated per RECIST v1.1. Pharmacokinetics (AUC21/AUC7, Cmax) for ladiratuzumab vedotin (ADC, TAB, MMAE) and antidrug antibody (ATA) incidence were also analyzed.