660MO First-in-human study of SGN-B7H4V, a B7-H4-directed vedotin ADC, in patients with advanced solid tumors: Preliminary results of a phase I study (SGNB7H4V-001)

B7-H4 is a B7 immune checkpoint ligand expressed at low levels in normal tissue and is upregulated in solid tumors, including breast, ovarian, and endometrial cancers. SGN-B7H4V is an investigational vedotin ADC comprising a B7-H4-directed monoclonal antibody conjugated to monomethyl auristatin E via a protease-cleavable linker. We report first results from dose escalation (Part A) of this ongoing phase 1 study. SGNB7H4V-001 is a first-in-human, multicenter study evaluating the safety, tolerability, pharmacokinetics, and antitumor activity (objective response rate per RECIST v1.1) of SGN-B7H4V in patients with advanced solid tumors. Part A enrolled patients with histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumors irrespective of B7-H4 expression. Patients received SGN-B7H4V on Days 1 and 8 of a 21-day cycle (2Q3W, 0.75, 1.0, 1.25, or 1.5 mg/kg), or on Days 1 and 15 of a 28-day cycle (2Q4W, 1.25, 1.5, 1.75, or 2.0 mg/kg). As of 10 March 2023, 75 patients were enrolled and received SGN-B7H4V. In 2Q3W (n=35), 3 patients (8.6%) had dose-limiting toxicities (DLTs) of hyperglycemia (1.25 mg/kg), arterial embolism (1.5 mg/kg), and neutropenia (1.5 mg/kg). The most common TEAEs across doses were fatigue (20.0%), peripheral sensory neuropathy (20.0%), and neutropenia (17.1%). The most common grade ≥3 TEAE was neutropenia (14.3%). In 2Q4W (n=40), 2 of 39 DLT-evaluable patients (5.1%) had DLTs of peripheral sensory neuropathy (1.5 mg/kg) and transaminitis (2.0 mg/kg). The most common TEAEs were fatigue (27.5%), peripheral sensory neuropathy (27.5%), and nausea (22.5%). The most common grade ≥3 TEAEs were anemia, dyspnea, hypotension, and pneumonia (5.0% each). Confirmed objective responses (starting at 0.75 mg/kg) were observed in evaluable patients with breast (7/25 patients), ovarian (2/15 patients), endometrial (1 [complete response]/16 patients), and biliary tract cancers (2/9 patients). SGN-B7H4V showed a manageable safety profile in patients with advanced solid tumors. Responses were observed at all tested dose levels and across various tumor types. Dose expansion in select tumor types is planned.