Celldex Therapeutics, Inc. (NASDAQ: CLDX) today announced the presentation of promising clinical data on CDX-011 in metastatic melanoma at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois. The Phase 2 study has met its primary endpoint and the results support additional studies in this indication. CDX-011 is an antibody-drug conjugate (ADC) in Phase 2 development for the treatment of melanoma and advanced breast cancer. In addition, in a separate presentation today at ASCO, the Company presented the study design for its recently initiated Phase 2 trial of CDX-1307 in bladder cancer. CDX-1307 is an antibody-based cancer vaccine candidate and is being evaluated as a treatment for bladder cancer.
“Further development is warranted for both candidates and we look forward to reporting additional clinical data in the near future.”
"Both CDX-011 and CDX-1307 have demonstrated tremendous potential for the treatment of the most difficult to treat cancers," said Anthony Marucci, President and Chief Executive Officer of Celldex Therapeutics. "Further development is warranted for both candidates and we look forward to reporting additional clinical data in the near future."
CDX-011 Phase 2 Melanoma Study Results
In the poster entitled Frequent Dosing and GPNMB Expression with CDX-011 (CRO11-vcMMAE), an Antibody-Drug Conjugate (ADC), in Patients with Advanced Melanoma, Celldex described updated results from the Phase 2 portion of the multicenter, open-label Phase 1/2 study of CDX-011 in patients with unresectable Stage III/IV melanoma. A total of 34 patients were enrolled in the Phase 2 expansion and the primary activity endpoint of overall response rate (ORR) in the cohort was achieved with an ORR of 15%. Median progression free survival (PFS) was 3.9 months. CDX-011 was found to be active in advanced melanoma patients in the study.
In the Phase 2 expansion study, CDX-011 was administered at the pre-defined maximum tolerated dose (MTD) once every three weeks. A more frequent dosing schedule at MTD was evaluated in two additional, parallel dose-escalation arms in which patients received CDX-011 weekly>
CDX-011 consists of the potent cellular toxin MMAE conjugated to a fully-human monoclonal antibody (CR011) to GPNMB. The destruction of GPNMB-expressing cells, or transmembrane glycoprotein NMB, a novel glycoprotein expressed in over 80% of melanomas, may be involved in growth delay and reduction of a tumor's metastatic potential. CDX-011 is designed to be stable in the bloodstream but to release MMAE upon internalization in GPNMB-expressing tumor cells, resulting in a targeted cell-killing effect. 83% (33/40) of patients with tumor sample analyzed by immunohistochemistry to date were positive for GPNMB expression. Preliminary data suggest an increase in PFS in patients with high tumoral GPNMB expression. The subset of seven patients, whose tumors were found to express high amounts of GPNMB, and who were treated at the maximum tolerated doses across all dosing schedules, demonstrated a median PFS of 4.9 months. The development of rash, which may be associated with the presence of GPNMB in the skin correlated with greater PFS. The most frequent treatment-related adverse events included rash, fatigue, alopecia (hair loss), pruritus, diarrhea and neuropathy.
CDX-1307 Bladder Cancer Study Design
In the poster entitled A Randomized Phase II Study of a Novel Antigen-Presenting Cell-Targeted hCG-β Vaccine (the CDX-1307 Regimen) in Muscle-Invasive Bladder Cancer, Celldex describes the study design for its Phase 2 trial of CDX-1307 in bladder cancer initiated in May of 2010. Recently CDX-1307 successfully completed a Phase 1 study in epithelial cancer.
In the multi-center Phase 2 controlled trial, 60 chemotherapy-naive patients with newly diagnosed, non-metastatic, resectable, muscle invasive hCG-beta positive bladder cancer will be randomized to receive either a neoadjuvant gemcitabine/cisplatin chemotherapy (GC) or CDX-1307 in combination with GC, poly-ICLC (PIC) and resiquimod (R) (the CDX-1307 regimen). The CDX-1307 dual mechanism of action shows that cytotoxic T cell responses specific to hCG-beta can directly kill tumor cells and that humoral anti-hCG-beta responses may neutralize anti-hCG-beta activity.
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