Vedotin Antibody-Drug Conjugate: Focus of First-in-Human Study in Advanced Solid Tumors

By: Joshua D. Madera, MD
Posted: Thursday, November 30, 2023

Use of an investigational agent called SGN-B7H4V in patients with advanced solid tumors, including 25 patients with breast cancer, may prove to be an effective treatment strategy, according to the preliminary results of a recent trial, presented at the European Society for Medical Oncology (ESMO) Congress 2023 (Abstract 660MO). In addition to its efficacy, this B7-H4–directed vedotin antibody-drug conjugate also seemed to have a favorable safety profile, according to Cesar A. Perez, MD, of the Sarah Cannon Research Institute at Florida Cancer Specialists, Orlando, and colleagues.

A total of 75 patients with histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumors were recruited for the study. Patients were randomly assigned to receive SGN-B7H4V on days 1 and 8 of the 21-day cycle or days 1 and 4 of the 28-day cycle. The amount of drug administered was gradually increased using a dose-escalation paradigm.

The study findings revealed that the most common treatment-related adverse events experienced by patients who received this treatment on the 21-day cycle were peripheral sensory neuropathy (20.0%), fatigue (20.0%), and neutropenia (17.1%). The most common grade 3 or greater treatment-related adverse events experienced by this treatment cohort was neutropenia (14.3%). Moreover, dose-limiting toxicities were documented in three patients and included neutropenia, an arterial embolism, and hyperglycemia. For patients in the 28-day cohort, the most common treatment-related adverse events were peripheral sensory neuropathy (27.5%), fatigue (27.5%), and nausea (22.5%). Grade 3 or greater treatment-related adverse events experienced by this cohort included pneumonia (5.0%), dyspnea (5.0%), hypotension (5.0%), and anemia (5.0%). Moreover, dose-limiting toxicities were documented in two patients and included transaminitis and peripheral sensory neuropathy.

In terms of efficacy, confirmed objective responses (starting at 0.75 mg/kg of SGN-B7H4V) were observed in 7 of 25 evaluable patients with breast cancer. Responses were also observed in a few patients with ovarian, endometrial, and biliary tract cancers.

Disclosure: For full disclosures of the study authors, visit cslide.ctimeetingtech.com.

ESMO Congress 2023