Celldex Therapeutics Initiates Phase 1/2 Study Of Varlilumab

(RTTNews) - Celldex Therapeutics, Inc. (CLDX) announced the initiation of an open-label, Phase 1/2 safety and tolerability study examining the investigational combination of varlilumab and sunitinib or SUTENT in patients with metastatic clear cell renal cell carcinoma or CC-RCC.

Varlilumab is Celldex's fully human monoclonal agonist antibody that binds and activates CD27, a critical co-stimulatory molecule in the immune activation cascade. Sunitinib is approved by the FDA as monotherapy for the treatment of advanced renal cell carcinoma or RCC, as well as certain advanced gastrointestinal stromal tumors and pancreatic neuroendocrine tumors. Varlilumab is currently being studied in four Phase 1/2 combination studies, and additional combination studies will be initiated in 2015.

Sunitinib blocks the function of receptor tyrosine kinases (RTKs), of which several are implicated in tumor growth, angiogenesis and metastasis. Sunitinib was selected for an investigational combination with varlilumab because it has demonstrated the potential to modulate anti-tumor immunity and reverse immune suppression in the tumor microenvironment. Varlilumab strengthens or creates an immune response against a new antigen, or target; therefore, a synergistic combination of sunitinib and varlilumab may elicit stronger responses in the immune system to fight CC-RCC and potentially other cancers.

In Celldex's Phase 1 study of varlilumab in multiple solid tumors, promising signs of clinical activity in patients with refractory CC-RCC were observed, including a durable partial response (13.0+ months) that has continued to decrease in tumor volume over time and prolonged stable disease (4 patients with a range of 5.3 to 33.0+ months).

The Phase 1 portion of the study will assess the safety and tolerability of varlilumab at 0.3, 1.0 and 3.0 mg/kg combined with sunitinib at 50 mg in order to identify a recommended dose for the Phase 2 portion of the study. In both phases of the trial, varlilumab will be administered once every three weeks for up to eight six-week cycles (a total of up to 16 varlilumab doses).

In each six-week cycle, sunitinib 50mg will be administered orally once daily for four weeks followed by two weeks without administration. The primary objective of the Phase 2 portion of the study is to assess the preliminary anti-tumor efficacy of the varlilumab/sunitinib combination measured by the overall response rate (ORR). Secondary objectives include safety and tolerability, pharmacokinetics, immunogenicity and further assessment of anti-tumor activity across a broad range of endpoints. The study is anticipated to include up to 10 sites in the United States and enroll approximately 60 patients.