Celldex Therapeutics (CLDX) presented two programs at the 2018 American Society of Clinical Oncology Annual Meeting. Data from the Phase 1/2 study of Celldex's varlilumab, a CD27 targeting investigational immune-activating antibody, and Bristol-Myers Squibb's (BMY) Opdivo, or nivolumab, an anti-PD1 immunotherapy, for patients with ovarian cancer and colorectal cancer, were presented. In addition, an overview of the Phase 2 study of the anti-ErbB3 antibody CDX-3379 in combination with Erbitux in advanced head and neck squamous cell cancer was presented in a "clinical trials in progress" poster session. Varlilumab was featured in an oral presentation that highlighted the ongoing Phase 2 study of varlilumab in combination with Opdivo. The Phase 1/2 study includes cohorts in ovarian cancer, colorectal cancer, head and neck squamous cell carcinoma, renal cell carcinoma and glioblastoma, with data from ovarian cancer and colorectal cancer patients included in the presentation. The majority of patients enrolled in the study had baseline tumors that were mostly "cold" with low expectation of responding to checkpoint inhibition therapy. The combination was well tolerated at all varlilumab dose levels tested. One patient with PD-L1 negative, MSI-high disease experienced a confirmed partial response in the Phase 2 study portion and continues on treatment. Of note, a patient with PD-L1 negative disease, initially considered MMR proficient as determined by standard screening laboratory analysis, achieved a near complete response in the Phase 1 portion of the study, which now continues at 35 months. As part of this study, an additional molecular analysis was conducted on this patient's tumor. The tumor had a high mutational burden and mutations in genes regulating DNA repair, which together likely contributed to the response. DCR was 20%. CDX-3379 was featured in a "clinical trials in progress" poster presentation that highlighted the ongoing Phase 2 study of CDX-3379, a human monoclonal antibody designed to block the activity of ErbB3, in combination with Erbitux in patients with human papillomavirus negative, Erbitux-resistant, advanced head and neck squamous cell carcinoma. The proposed mechanism of action for CDX-3379 sets it apart from other drugs in development in this class due to its ability to block both ligand-independent and ligand-dependent ErbB3 signaling by binding to a unique epitope. It has a favorable pharmacologic profile, including a longer half-life and slower clearance relative to other drug candidates in this class. The multicenter, open-label, Simon two-stage design study is expected to enroll approximately 27 patients. The primary objective of the study is objective response rate. Secondary objectives include assessments of clinical benefit response, duration of response, progression-free survival and overall survival, and safety and pharmacokinetics associated with the combination. Four clinical trial sites are currently open to enrollment, and Celldex is targeting to complete enrollment to the first stage of the study by the end of the third quarter of 2018. The company continues to explore potential other opportunities in additional indications where ErbB3 is believed to play a role.
