AACR II: Antibody-Drug Conjugate Targets CLDN6/9 in Epithelial Ovarian Cancer
Posted: Monday, July 20, 2020
Despite advancements in the development of PARP inhibitors and other agents in gynecologic cancers, there is still a therapeutic void for patients with recurrent epithelial ovarian cancer. With that in mind, Erika P. Hamilton, MD, of the Sarah Cannon Cancer Institute, Nashville, and colleagues presented their findings during the 2020 American Association for Cancer Research (AACR) Virtual Annual Meeting II (Abstract CT124) of the first-in-human study of SC-004, an antibody-drug conjugate targeting CLDN6/9, in epithelial ovarian cancers. Among 19 evaluable patients, the best overall response of stable disease was reported in 73% of patients.
“SC-004 demonstrated low tolerability with a side-effect profile similar to other pyrrolobenzodiazepine-conjugated antibody-drug conjugates, along with insufficient evidence of activity to support continued investigation,” the investigators concluded.
In this open-label, phase I clinical trial, the safety, tolerability, and maximum tolerated dose of SC-004 were assessed in patients with platinum-resistant or -refractory epithelial ovarian cancers and endometrial cancer. SC-004 was administered intravenously at 0.005 to 0.3 mg/kg every 3 weeks (0.3 mg/kg was administered every 4 weeks). Treatment-emergent adverse events were defined as any adverse event that worsened from the first dose of SC-004 through 90 days after discontinuation of treatment. Membranous CLDN6 expression was assessed by immunohistochemistry.
The best overall response of stable disease was reported in 14 of 19 evaluable of patients; partial response was observed in one patient (5%), and progressive disease was reported in four patients. As for the safety profile associated with SC-004, the most common treatment-emergent adverse events were fatigue (38%), peripheral edema (33%), vomiting (33%), pleural effusion (25%), urinary tract infection (25%), maculopapular rash (25%), anemia (21%), abdominal pain (21%), diarrhea (21%), and decreased appetite (21%). A total of 13 patients (54%) died during the trial, mainly due to disease progression.
Disclosure: For full disclosures of the study authors, visit abstractsonline.com.