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.

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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.


  1. 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]