Sapna Pradyuman Patel, MD
Glembatumumab vedotin (CDX-011) induced a disease control rate (DCR) of 61% in patients with metastatic uveal melanoma, despite a low a low objective response rate (ORR) of 6%, according to results from the the phase II NCI9855 study.
There were no complete responses, 2 (6%) partial responses, and 17 patients (55%) with stable disease. Twelve patients (39%) experienced disease progression.
“We had 2 confirmed partial responses in patients with M1b and M1c disease of the liver,” said Sapna Pradyuman Patel, MD, assistant professor of melanoma medical oncology at MD Anderson Cancer Center, said when presenting the results at the 2017 World Congress of Melanoma.
The median duration of response was 8.6 months and the median duration of stable disease was 4.8 months, or 7 cycles. Eleven patients (35%) had stable disease for more than 100 days.
Glembatumumab vedotin (CDX-011) is a fully human monoclonal antibody-drug conjugate that targets glycoprotein NMB (gpNMB), a protein overexpressed by multiple tumor types, including uveal melanoma. Previous studies have shown that 86% of uveal melanomas express gpNMB.
NCI9855 was a phase II, open-label, single-arm, multicenter study. Patients were treated at the recommended phase II dose of 1.9 mg/kg of glembatumumab IV every 3 weeks. Investigators assessed response every 6 weeks using RECIST 1.1. The target ORR was 20%.
The primary endpoint was ORR. Secondary endpoints included progression-free survival (PFS), overall survival (OS), DCR, and gpNMB expression.
From January 2016 to September 2017, 73 patients enrolled in the study and 34 were treated on-protocol. Results from 31 patients were included in this analysis. Two patients remained on treatment.
The median age was 56 (range, 28-79) and just under half the cohort was female (47%). Three-quarters of patients had an ECOG performance status of 0 and the remainder had a status of 1.
The liver was the most common site of metastases (91%), followed by the lungs (35%), lymph nodes (26%), and deep soft tissue (26%).
The median PFS was 3.2 months and the median OS was 11.8 months in the total patient population. The median PFS was 5.5 months in the disease control cohort and median OS has not been reached.
Neutropenia (41%), maculopapular rash (6%), and pruritus (6%) were the most common grade 3 adverse events. Only neutropenia (15%) was grade 4 in severity.
“Across the study, the most common grade 3/4 treatment-related adverse event was neutropenia,” Patel said. “This was reversible and supported in subsequent cycles with the use of growth factor.”
Patel said that, in contrast to previous analyses, rash in cycle 1 did not correlate with response or PFS in this study.
Investigators assessed gpNMB expression at baseline and again at 21 days. Patel said that gpNMB expression was high across the study, with any tissue samples exhibiting 100% expression and 3+ intensity.
“This did not appear to change in response to 1 dose of treatment,” she said. “Additional tissue studies are underway to investigate percent of drug saturation to this high target.”
She added that exploratory immune correlates are underway to provide insight into combination strategies and induction of antigen release.
Patel S. A phase II study of glembatumumab vedotin for metastatic uveal melanoma. Presented at: 2017 World Congress of Melanoma; October 18-21, 2017; Brisbane, Australia. Presentation SMR09-5.<<< View more from the World Congress of Melanoma