Celldex Therapeutics Initiates Phase I/II Study

Celldex Therapeutics, Inc. recently announced it has initiated an open-label Phase I/II safety and tolerability study of glembatumumab vedotin in patients with unresectable stage IIIB or IV, gpNMB-expressing, advanced or metastatic squamous cell carcinoma (SCC) of the lung, who have progressed on prior platinum-based chemotherapy. Glembatumumab vedotin is a fully human monoclonal antibody-drug conjugate (ADC) that targets gpNMB, a protein overexpressed by multiple tumor types, including SCC of the lung, where approximately 85% of patients overexpress the marker. Overexpression of gpNMB has been shown to promote the invasion and metastasis of cancer and has been associated with poor clinical outcome. Celldex has entered into a collaborative relationship with PrECOG, LLC, which represents a research network established by the Eastern Cooperative Oncology Group (ECOG), and PrECOG, LLC will conduct the study.

“While checkpoint inhibitor therapy has been an important development for patients with squamous cell lung cancer, the majority of patients still require new, effective treatment options, especially targeted therapies,” said Thomas Davis, MD, Executive Vice President and Chief Medical Officer of Celldex Therapeutics. “gpNMB, the target of glembatumumab vedotin, is strongly expressed in the vast majority of squamous cell lung cancers. Glembatumumab vedotin has consistently induced notable response rates in other difficult to treat cancers that overexpress gpNMB. We hope to elicit similar activity in squamous cell carcinoma and look forward to completing this study.”

Glembatumumab vedotin is currently being evaluated in patients with metastatic triple negative breast cancers that overexpress gpNMB in the registrational METRIC study, as well as in a Phase II study in patients with advanced melanoma who have progressed after at least one checkpoint inhibitor therapy and, if applicable, BRAF- or MEK-targeted therapy. It has been previously evaluated in a Phase II study in advanced breast cancer (the EMERGE study), a Phase I/II study in advanced breast cancer and a Phase I/II study in patients with unresectable stage III or IV melanoma. Also, Celldex and the National Cancer Institute (NCI) have entered into a Cooperative Research and Development Agreement (CRADA) under which the NCI is sponsoring two studies of glembatumumab vedotin – one in uveal melanoma and one in pediatric osteosarcoma. Both studies are currently open to enrollment.

This Phase I/II study will enroll patients with gpNMB-positive stage IIIB or IV non-small cell lung cancer (NSCLC) of squamous histology who have previously been treated with platinum-based chemotherapy. gpNMB positivity will be determined by a greater than, or equal to, 5% gpNMB expression in tumor epithelial cells. Glembatumumab vedotin will be administered once every 3 weeks until disease progression or intolerance. The study is expected to include 10 sites in the United States.

The study will include a dose-escalation phase followed by a two-stage Phase II portion (Simon two-stage design). The Phase I, dose-escalation portion of the study will assess the safety and tolerability of glembatumumab vedotin at the current dose of 1.9 mg/kg and then 2.2 mg/kg in order to determine whether higher dosing is feasible in this population. The first stage of the Phase II portion will enroll approximately 20 patients, and if at least two patients achieve a partial response or complete response, a second stage may enroll an additional 15 patients. The primary objective of the Phase II portion of the study is to assess the anti-tumor efficacy of glembatumumab vedotin in squamous cell lung cancer as measured by objective response rate (ORR). Secondary objectives of the study include analyses of safety and tolerability and further assessment of anti-tumor activity across a broad range of endpoints.

Lung cancer is the leading cause of cancer related deaths in the world, with an estimated one million new cases worldwide and around 216,000 in the U.S. annually. Non-small cell lung cancer (NSCLC) represents more than 80% of all lung cancers, and squamous cell carcinoma (SCC) of the lung accounts for approximately 30% to 40% of NSCLC. While new treatment options, especially targeted therapies, have become available for patients with adenocarcinoma, another type of NSCLC, clinical studies have not identified targeted therapies with major benefits for patients with SCC of the lung. Recent improvements for patients with SCC of the lung include checkpoint immunotherapy; however, not all patients respond to this treatment, and new therapeutic options are needed. Approximately 85% of patients with SCC of the lung have tumors that overexpress gpNMB, the target of glembatumumab vedotin.

Glembatumumab vedotin (CDX-011) is a fully human monoclonal antibody-drug conjugate (ADC) that targets glycoprotein NMB (gpNMB). gpNMB is a protein overexpressed by multiple tumor types, including breast cancer, melanoma, lung cancer, head and neck cancer, uveal melanoma, osteosarcoma, pancreatic cancer and glioblastoma. gpNMB has been shown to be associated with the ability of the cancer cell to invade and metastasize and to correlate with reduced time to progression and survival in breast cancer. The gpNMB-targeting antibody, CR011, is linked to a potent cytotoxic, monomethyl auristatin E (MMAE), using Seattle Genetics’ proprietary technology. Glembatumumab vedotin is designed to be stable in the bloodstream but to release MMAE upon internalization into gpNMB-expressing tumor cells, resulting in a targeted cell-killing effect. Glembatumumab vedotin is in development for the treatment of locally advanced or metastatic breast cancer with an initial focus in triple negative disease, stage III and IV melanoma, squamous cell lung cancer, uveal melanoma and osteosarcoma.

Celldex is developing targeted therapeutics to address devastating diseases for which available treatments are inadequate. Its pipeline is built from a proprietary portfolio of antibodies and immunomodulators used alone and in strategic combinations to create novel, disease-specific therapies that induce, enhance or suppress the body’s immune response. For more information, visit www.celldex.com.