On November 17, 2017 Celldex Therapeutics, Inc. (Nasdaq:CLDX) reported that enrollment has opened in its open-label Phase 2 study of CDX-3379 in combination with cetuximab in patients with cetuximab-refractory, advanced head and neck squamous cell carcinoma (HNSCC) (Press release, Celldex Therapeutics, NOV 17, 2017, View Source [SID1234522129]). CDX-3379 is Celldex’s human monoclonal antibody that selectively binds and inhibits the activity of ErbB3, also known as HER3. ErbB3 may be an important receptor regulating cancer cell growth and survival as well as resistance to targeted therapies, and it is expressed in many cancers, including HNSCC. Cetuximab, which is marketed under the brand name Erbitux, is a monoclonal antibody that specifically binds EGFR and inhibits its signaling pathway.

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"ErbB3 is a central enabler for known oncogenic drivers, including EGFR, a validated target with approved targeted therapeutics, such as cetuximab. Unfortunately, resistance to targeted treatments often develops, and we believe CDX-3379 may play an important role in overcoming it. CDX-3379 specifically blocks ErbB3 with potent binding affinity and locks it into a deactivated state, blocking both its mechanisms of interacting with its ligand and also with other oncogenic drivers," said Christopher Turner, M.D., Vice President, Clinical Science at Celldex Therapeutics. "In a Phase 1b study, we saw evidence of antitumor activity among the nine patients with HNSCC who were treated with CDX-3379 in combination with cetuximab, including a durable complete response in a patient who had previously progressed on single-agent cetuximab."

Study Overview
This multicenter, open-label, Phase 2 study of CDX-3379 in combination with cetuximab will enroll approximately 30 patients with cetuximab-resistant, advanced HNSCC who have previously been treated with an anti-PD1 checkpoint inhibitor, a population with limited options and a particularly poor prognosis. CDX-3379 (12 mg/kg) will be administered once every three weeks, and cetuximab (400 mg/m2 initial dose, then 250 mg/m2) will be administered every week. Treatment will continue until disease progression or intolerance, and assessments will occur every six weeks.

Using a Simon two-stage design, the first stage of study will enroll 13 patients, and if at least one patient achieves a partial response or complete response, enrollment will progress to the second stage. The primary objective is to assess the anti-tumor efficacy of CDX-3379 in combination with cetuximab as measured by objective response rate. Secondary objectives of the study include analyses of safety, pharmacokinetics, immunogenicity and further assessment of anti-tumor activity across a broad range of endpoints, such as clinical benefit rate, duration of response, progression-free survival and overall survival, for the combination. Tumor response assessments will be performed by the investigator according to standardized, objective response criteria (RECIST 1.1).

More information about this study is available on www.clinicaltrials.gov (Identifier: NCT03076372).

About CDX-3379
CDX-3379 is a human immunoglobulin G1 lambda (IgG1λ) monoclonal antibody that selectively binds and inhibits ErbB3 activity. ErbB3 may be an important receptor regulating cancer cell growth and survival as well as resistance to targeted therapies, and it is expressed in many cancers, including head and neck, thyroid, breast, lung and gastric cancers, as well as melanoma. 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. CDX-3379 also has potential to enhance anti-tumor activity and/or overcome resistance in combination with other targeted and cytotoxic therapies to directly kill tumor cells.

Erbitux is a registered trademark of Eli Lilly & Co.