A novel, first-in-class, agonist anti-CD27 monoclonal antibody was found to be clinically and biologically active, according to early findings published in the Journal of Clinical Oncology.

In this phase I first-in-human study of varlilumab, doses at 0.1 to 10 mg/kg were well tolerated by patients with advanced solid tumors. In addition, antitumor activity was also observed. One heavily pretreated patient with stage IV disease renal cell carcinoma (RCC) experienced durable and significant tumor regression, with 78% tumor shrinkage and a partial response that persisted for 2.3 years without additional anticancer therapy, reported Howard A. Burris, MD , of the Sarah Cannon Research Institute, Tennessee Oncology, Nashville, and his colleagues (J Clin Oncol. 2017 May 2. doi: 10.1200/JCO.2016.70.1508 ).

Another RCC patient achieved an 18% shrinkage of target lesions, and has been able to maintain stable disease status for nearly 4 years without the need for additional therapy. This patient had previously progressed after treatment with everolimus and sorafenib for 3 months and capecitabine for 9 months.

In addition, eight patients achieved stable disease for more than 3 months while on the study.

“This phase I study of varlilumab provides proof of concept and a rationale for further study in combination with immunotherapies and traditional therapies,” wrote Dr. Burris and his colleagues. “Therapy that targets multiple nonredundant pathways that regulate immune responses may be synergistic and enhance antitumor immune responses.”

The study was conducted to assess the safety, pharmacokinetics, pharmacodynamics, and activity of varlilumab when used as a single agent in patients with advanced solid tumors.

The entire cohort included 56 patients enrolled at nine centers, and the dose escalation component included 25 patients. The expansion part of the trial included 16 patients with melanoma and 15 patients with RCC.

The most common cancer type in the dose-escalation phase was colorectal cancer (40%) followed by melanoma (28%). All patients had stage IV disease and, in general, were heavily pretreated.

A median of 4 doses was administered to the cohort (1-21), and, in the dose escalation phase, the 10 mg/kg was reached without identifying a maximum tolerated dose. Only one patient experienced a dose limiting toxicity, which was grade 3 asymptomatic hyponatremia (129 mmol/L) that occurred at the 1.0-mg/kg dose level.

A total of eight patients achieved stable disease, including four with RCC (duration of stable disease: 5.3, 5.6, 9.3, and 47.3 months), three with melanoma (3.8, 7.3, and 11.5 months), and one patient with colorectal adenocarcinoma (5.7 months).


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