259P Weekly ladiratuzumab vedotin monotherapy for metastatic triple-negative breast cancer

Abstract

LIV-1 is highly expressed in breast cancer. Ladiratuzumab vedotin (LV) is an investigational anti-LIV-1 antibody-drug conjugate with a protease-cleavable linker conjugated to monomethyl auristatin E (MMAE). LV 2.5 mg/kg given every 3 weeks (q3w) was generally well tolerated and has demonstrated encouraging efficacy in patients with pre-treated metastatic triple-negative breast cancer (mTNBC). Here, we evaluated the efficacy and tolerability of weekly LV dosing (q1w). 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. As of March 19, 2021, 81 patients were treated in Part E (median age 55 years, female 100%, ECOG-0 62%, subtype: mTNBC 49%, HR+/HER2- 51%). No dose limiting toxicities occurred with either LV 1.0, 1.25, or 1.5 mg/kg q1w. At LV 1.5 mg/kg, neutropenia was reported in 6 of 9 patients (66%; 1 Grade 1, 1 Grade 2, 1 Grade 3, and 3 Grade 4). Subsequent enrollment continued only in the LV 1.25 mg/kg cohort. The most common treatment emergent adverse events (TEAEs) observed with LV 1.25 mg/kg q1w (n=52) were nausea (60%), fatigue (58%), peripheral sensory neuropathy (54%), decreased appetite (44%), and constipation (39%). The most common ≥ Grade 3 TEAEs were neutropenia (21%), fatigue (14%), and hyperglycemia, hypokalemia, and hypophosphatemia (12% each). The most common serious adverse events were pneumonia (6%) and abdominal pain (4%). In the 29 patients with 2L mTNBC who received LV 1.25 mg/kg, the confirmed objective response rate was 28% (95% CI: 13, 47). Pharmacokinetic analyses indicate q1w dosing reduced peak-trough fluctuations, lowered Cmax while maintaining a higher Ctrough compared to q3w dosing. LV 1.25 mg/kg q1w is associated with a manageable safety profile and favorable preliminary efficacy data in patients with 2L mTNBC. Further studies of LV q1w in patients with breast cancer and other tumors are underway.