Celldex Therapeutics, Inc. (NASDAQ: CLDX) today announced the results of a positive Phase 2 study of CDX-011 (formerly CR011-vcMMAE), in patients with heavily pre-treated, locally advanced or metastatic breast cancers. As presented today at the 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium, the primary efficacy endpoint for the study has been met with significant antitumor activity in patients whose tumors express the target GPNMB. In addition, encouraging results were seen in patients with “triple-negative disease” where treatment options are relatively limited due to lack of hormone receptor or HER2-neu expression.
CDX-011 is the first candidate from the Company’s antibody-drug conjugate (ADC) platform, which utilizes fully human monoclonal antibodies to deliver the potent cellular toxin, MMAE, directly to tumor cells by targeting GPNMB. GPNMB is a glycoprotein frequently expressed in a number of tumor types and associated with cancer progression and recurrence. CDX-011 uses the Seattle Genetics MMAE ADC technology, which has established a very promising antitumor effect in advanced clinical studies.
“As seen in this study, treatment with CDX-011 can induce disease regression and stabilization,” said Thomas Davis, M.D., Senior Vice President and Chief Medical Officer of Celldex Therapeutics. “We are very encouraged to see such positive results in patients with triple negative disease – or those with advanced, refractory and heavily pre-treated breast cancers — where there is a clear unmet medical need. Moving forward, we are planning expanded Phase 2 development focused on patients with tumors expressing GPNMB.”
The Phase 2 study investigated the safety, tolerability and efficacy of CDX-011 in locally advanced or metastatic breast cancer patients who were heavily pre-treated (median of seven prior regimens). The study confirmed the safety of CDX-011 at the pre-defined maximum dose level (1.88 mg/kg) in 6 patients. An additional 28 patients were enrolled as an expanded Phase 2 cohort (for a total of 34 treated patients at 1.88 mg/kg, the Phase 2 dose) to evaluate the progression-free survival (PFS) rate at 12 weeks. As previously seen in melanoma patients, the 1.88 mg/kg dose was well tolerated in this patient population. The primary activity endpoint, which called for at least 5 of 25 (20%) patients in the Phase 2 study portion to be progression-free at twelve weeks, has been met. To date, 9 of 26 (35%) evaluable patients are without progression of disease at twelve weeks.
In addition, at the Phase 2 dose level, 4 of 32 (13%) evaluable patients achieved confirmed or unconfirmed Partial Responses (PR) while 15 of 25 (60%) evaluable patients with measurable disease experienced some reduction in tumor size. GPNMB expression was identified in 10 of 14 (71%) of analyzed tumor samples and treatment with CDX-011 was associated with improved outcomes in all activity parameters in patients whose tumors expressed GPNMB. Notably, in patients who received the Phase 2 dose and whose tumors expressed GPNMB, 2 of 7 (29%) had confirmed Partial Responses, 5 of 7 (71%) had decreases in tumor size, and all 7 achieved at least stable disease with duration from 17.3 to 26.9 weeks. The median PFS in all patients was 9.1 weeks, but in patients whose tumors expressed GPNMB, median PFS was 18.3 weeks, compared to median PFS of 5.9 weeks for patients whose tumors did not express GPNMB. In patients with triple negative disease, 5 of 7 (71%) analyzed samples expressed GPNMB, 7 of 9 (78%) evaluable patients had tumor shrinkage, and the median PFS for these patients was 17.9 weeks.