Celldex Therapeutics and Bristol Myers-Squibb (BMS) have started a Phase I/II dose escalation and cohort expansion trial of the combination of varlilumab and Opdivo (nivolumab) to treat advanced refractory solid tumours.
The trial is designed to evaluate the safety and tolerability of this combination in adults with advanced non-small cell lung cancer (NSCLC), metastatic melanoma (MEL), colorectal cancer (CRC), ovarian cancer, and head and neck squamous cell carcinoma (SCCHN).
Celldex's CD27 targeting investigational immune-activating antibody, varlilumab is a fully human monoclonal antibody that targets CD27, a critical molecule in the activation pathway of lymphocytes.
BMS's immunotherapy Opdivo is a human programmed death receptor-1 (PD-1) blocking antibody that binds to the PD-1 receptor expressed on activated T-cells.
The trial is designed to address the hypothesis that the combination of these two mechanisms enhances the anti-tumour activity compared to either agent alone.
As part of the clinical trial collaboration signed between the two firms, Celldex will be responsible for conducting the trial, while development costs will be shared.
The Phase I dose-escalation portion of the trial will evaluate the safety and tolerability of varlilumab at doses ranging from 0.1 to 10mg/kg when administered with Opdivo (3mg/kg).
After dose escalation, a Phase II portion of the trial will include five disease specific groups, with either 18 (CRC, SCCHN, ovarian) or 35 (NSCLC and MEL) patients in each group.
In this portion of the trial, patients will be treated with varlilumab until intolerance, disease progression or completion of up to four cycles.
The primary objective of the Phase II portion is overall response rate, while secondary objectives include pharmacokinetics assessments, determining the immunogenicity of varlilumab when given in combination with Opdivo.
The trial's secondary objectives also include further evaluation of the anti-tumour activity of combination treatment, including duration of response, time to response, progression-free survival and overall survival.
Currently, Varlilumab is being evaluated in two Phase I/II combination trials, and several additional combination trials will be started in 2015.
Earlier, the US Food and Drug Administration (FDA) approved Opdivo injection for intravenous use to treat patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor.