NEEDHAM, Mass. ( TheStreet) -- A targeted cancer drug, CDX-011, from Celldex Therapeutics (CLDX - Get Report) delayed tumor growth and prolonged survival in patients with an advanced and aggressive form of breast cancer compared to single-agent chemotherapy, according to final results from a mid-stage study presented Saturday.
Dr. Denise Yardley of the Sarah Canon Research Institute said the CDX-011 data showed a "clear signal of activity" because the breast cancer patients enrolled in the study typically respond poorly to currently approved medicines. However, the data presented Saturday was derived from a small number of patients, meaning Celldex will have to run a larger, confirmatory study to more definitively vet CDX-011's benefit, she cautioned.
Celldex plans to meet soon with the U.S. Food and Drug Administration to get sign-off on a plan for a confirmatory study of CDX-011, which if positive, could lead to an accelerated approval, said CEO Anthony Marucci.
The CDX-011 phase II results were released at the San Antonio Breast Cancer Symposium. Interim results from the same study were announced by Celldex last May.CDX-011 is a monoclonal antibody drug conjugate. The antibody portion latches on to cancer cells that contain a protein known as GPNMB, which has been shown to correlate with poorer outcomes in breast cancer patients. When the CDX-011 antibody attaches to GPNMB-expressing tumor cells, it releases a toxic chemotherapy payload. This "drug conjugate" was licensed from Seattle Genetics (SGEN - Get Report) and is the same one used in the newly approved lymphoma drug Adcetris. Celldex designed the phase II study to test the theory that CDX-011 would work better in breast cancer patients with tumors containing high levels of the GPNMB protein. The 120 patients enrolled in the study were screened to make sure they all had at least some tumor cells that contained GPNMB but were then separated into high-expression and low-expression groups. All the patients had advanced breast cancer that was no longer responding to a median of 5-6 prior therapies. Two-thirds of patients were treated with injections of CDX-011 while the remaining third of patients were treated with chemotherapy of the doctor's choice. In patients with triple-negative breast cancer that also contained high levels of GPNMB -- a group of patients most difficult to treat -- treatment with CDX-011 led to a 33% response rate compared to no responses in patients treated with "investigator's choice" chemotherapy. CDX-011 doubled the time before tumors started to grow again to a median of 3 months compared to 1.5 months for control arm patients. Median overall survival also almost doubled in the CDX-011-treated patients to a median 10 months versus 5.5 months for patients in the control arm. Results were statistically significant although the benefit was derived from an analysis that included just 12 patients treated with CDX-011 and 4 patients treated with investigator's choice chemotherapy. Based on these data, Celldex would like to run a confirmatory trial for CDX-011 in patients with triple-negative breast cancer that also contains high levels of GPNMB, pending FDA agreement. Approximately 5,000 to 9,000 breast cancer patients in the U.S. fit this category, according to various estimates. CDX-011 may benefit a broader group of 30,000 to 40,000 breast cancer patients in the U.S. with tumors that contain high levels of GPNMB. Thirty-two percent of GPNMB high expressers responded to CDX-011 treatment compared to a 13% response rate in patients treated in the control arm in the phase II study. CDX-011 delayed the re-growth of tumors by a median 2.7 months compared to 1.5 months for the control arm. Median overall survival was 10 months for CDX-011 versus 5.7 months for the control arm. These results, culled from a subgroup of 38 patients, trended in favor of CDX-011 but were not statistically significant. CDX-011 does not appear to benefit breast cancer patients with tumors that contain minimal levels of the GPNMB protein. When all 122 patients in the phase II study were analyzed, treatment with CDX-011 resulted in a 16% response rate compared to a 14% response rate in patients treated with investigator's choice. The time to tumor re-growth and overall survival were essentially identical between both groups of patients. Celldex Chief Medical Officer Tom Davis said different cutoff levels of GPNMB expression were examined in the phase II study, with 25% and above determined to be the level at which CDX-011 showed the greatest efficacy. With relatively few patients to examine in the phase II study, however, the margin of error is greater. This raises the risk that the benefit of CDX-011 seen in the small phase II study may disappear when a larger study of the drug is conducted. -- Reported by Adam Feuerstein in Boston. Follow @AdamFeuerstein