They presented a "Retrospective Analysis" of the results of the PII of MT201 at ASCO. Although the primary endpoints were not met,as previously reported, the RA showed that patients with a
high EpCAM expression showed much better results.<g>
Final Data from a Phase 2 Trial Presented at ASCO Specifies Dose-dependent Activity of Adecatumumab (MT201)
Monday June 4, 7:00 am ET
BETHESDA, Md., June 4 /PRNewswire-FirstCall/ -- Micromet, Inc. (Nasdaq: MITI - News), a biopharmaceutical company focusing on the development of novel, proprietary antibody-based products for cancer, inflammatory and autoimmune diseases, today reported final data from the randomized phase 2 clinical trial of adecatumumab (MT201) in metastatic breast cancer (MBC) patients, including recent exploratory posthoc subgroup analyses.
Adecatumumab originated at Micromet and is being developed in collaboration with Merck Serono, a division of Merck KGaA, Darmstadt Germany.
The product candidate, a fully human monoclonal antibody targeting tumor cells overexpressing the epithelial cell adhesion molecule (EpCAM), was tested as a single agent at two dose levels to assess its efficacy and safety in patients with EpCAM-positive metastatic breast cancer (N=109).
EpCAM expression has been implicated to be a negative prognostic marker associated with strongly decreased overall survival in MBC patients.
The final data set of the Phase 2 clinical trial of adecatumumab in patients with metastatic breast cancer including new additional subgroup analyses was presented at the 43rd Congress of the American Society of Clinical Oncology (ASCO) in Chicago, IL. As previously reported, the primary endpoint of the clinical trial (i.e., 25 percent clinical benefit rate at week 24) was not reached. However, a significant prolongation of time-to- progression in patients treated with the higher dose of adecatumumab compared to patients receiving the lower dose was shown (p<0.05).
The additional analysis was triggered by the trend toward increased time- to-progression in patients treated with adecatumumab expressing "high" EpCAM levels as opposed to patients treated with adecatumumab with "low" EpCAM expression on their primary tumor tissue. This observation is in contrast to EpCAM expression being implicated as a negative prognostic marker associated with strongly decreased overall survival in MBC patients.
The retrospective analysis of the data set applied modified EpCAM cut-off criteria. Whereas the original criteria used to define a tumor's EpCAM expression as "high" allowed samples with both medium (2+) and high intensity (3+) staining in the immunohistochemistry (IHC), the retrospective analysis restricted "high" EpCAM to patients with high intensity (3+) staining specimens only. In a second step, various cut-off criteria for the required frequency of stained cells in those 3+ samples were applied.
Overall, all efficacy parameters of adecatumumab on disease progress (clinical benefit rate, time to tumor progression, progression free survival) improved with increasing EpCAM expression. Whereas only 2.9% of patients with "low" EpCAM expressing tumors were progression-free after 24 weeks of follow- up, this outcome was shown in 12.2% of patients in the original "high" EpCAM group. Applying the most stringent criteria for "high" EpCAM expression used in the retrospective analysis resulted in 22.2% of patients with high-EpCAM expressing tumors with no signs of disease progression after 24 weeks. Notably, 30% of patients receiving high-dose adecatumumab in this specific group did not progress up to week 24. The poster presentation with more detailed information has been filed with the SEC and can be viewed on the company's website at www.micromet-inc.com.
"While the previously reported data of this Phase 2 clinical trial already suggested activity of adecatumumab, this finding now is corroborated by the results of the retrospective analyses," the principal investigator, Dr. Ahmad Awada, Head of the Medical Oncology Clinic at Institute Jules Bordet in Brussels, Belgium, commented. "The finding of better clinical outcome in patients with truly high EpCAM expressing tumors confirms the targeted nature of adecatumumab and is in line with observations from other tumor-specific monoclonal antibodies in oncology like Herceptin®."
Adecatumumab was generally well tolerated with the observation of a dose- dependent incidence of adverse events (AE's). The most frequent AE's were fever, chills, diarrhea, hypertension, lymphopenia and elevation of pancreatic enzymes, and most AE's were of mild to moderate severity.
Adecatumumab is currently being explored for tolerability in combination with docetaxel in an ongoing phase 1b clinical trial in patients with metastatic breast cancer. An additional phase 1 clinical trial is currently planned to investigate further increased doses of adecatumumab and intensified dosing regimens in other EpCAM-expressing solid tumors such as colorectal cancer, lung cancer, gastric cancer, and ovarian cancer.
Snip
After the announced collaboration with Nycomed on MT203, the ones that still remain "Unpartnered", as shown on the table of their "pipeline" as per the Annual Report, are MT204 & MT110, which are on "Preclinical Phase".MT110 also targets EpCAM.
Of course, MT201, which targets EpCAM, & uses a combination of adecatumumab-Docetaxel Combo is the one that appears to be more advanced with a completed PIIa. That's the on in which they are collaborating with Merck Serono for breast cancer.
MT103, that targets CD19 & has completed a PI. is the one in which they are collaborating with MEDI for NHL.
Bernard |
