The first-in-class anti-CD27 antibody varlilumab demonstrated clinical activity among and was well-tolerated by patients with solid tumors, according to a study published in the Journal of Clinical Oncology.1
Varlilumab is being evaluated in an open-label, phase 1, dose-escalation trial among patients with solid and hematologic tumors. This analysis includes patients with solid tumors including renal cell carcinoma (RCC), hormone-refractory prostate cancer, ovarian cancer, colorectal adenocarcinoma (CRC), and non–small cell lung cancer.
The study enrolled 56 patients with stage IV disease; 25 participated in the dose escalation and 16 patients with RCC or melanoma were enrolled in expansion cohorts. The dose escalation phase evaluated 0.1, 0.3, 1.0, 3.0, and 10 mg/kg of varlilumab given over 90 min without prophylactic premedication.
Varlilumab exposure was dose-dependent and linear across dosing groups. T cell saturation occurred with doses of 1 mg/kg and higher.
Dose escalation did not identify a maximum tolerated dose, and patients received a median of 4 doses.
One patient discontinued treatment due to grade 3 asymptomatic hyponatremia that occurred 14 days after the last dose of varlilumab and spontaneously resolved. Other grade 3 adverse events — which did not lead to discontinuation — were decreased appetite and decreased lymphocyte count.
Most treatment-related toxicities were grade 1 or 2 in severity and included fatigue, rash, nausea, and diarrhea. Infusion reactions occurred in 3 patients, 2 of which were prevented with premedication prior to subsequent dosing.
Antitumor activity was noted among 9 patients. A patient with RCC experienced tumor regression and stable disease for at least 3.9 years. Four patients with RCC, 3 with melanoma, and 1 with CRC experienced disease stabilization for over 3 months.
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According to the authors, these findings “provide proof of concept and a rationale for further study in combination with immunotherapies and traditional therapies.” Additional studies of varlilumab are ongoing.
- Burris HA, Infante JR, Ansell SM, et al. Safety and activity of varlilumab, a novel and first-in-class agonist anti-CD27 antibody, in patients with advanced solid tumors. J Clin Oncol. 2017 May 2. doi: 10.1200/JCO.2016.70.1508 [Epub ahead of print]