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Final Data from Celldex Therapeutic's CDX-011 Phase 2 Study in Metastatic Breast Cancer Supports Overall Survival Benefit in Patients with High GPNMB Expression
Dec 8, 2012
--Broad activity with greatest benefit in patients with high GPNMB-expressing triple negative breast cancer--
--Data presented today in a poster session at San Antonio Breast Cancer Symposium--
While the study was not powered to demonstrate statistical significance between the arms, beneficial activity in targeted patient populations that highly expressed GPNMB was consistently observed and, in some cases, was statistically significant. Treatment of patients with both triple negative breast cancer and high GPNMB expression showed high overall response rates (ORR) for the CDX-011 arm (CDX-011 ORR of 33% vs 0% in the Investigator's Choice (IC) arm) and an overall survival and progression free survival (PFS) benefit for CDX-011 that reached statistical significance (CDX-011 median survival of 10.0 months vs IC of 5.5 months; p=0.003); (CDX-011 median PFS of 3.0 months vs IC of 1.5 months; p=0.008). In patients with high GPNMB expression, a high response rate was observed in the CDX-011 arm (CDX-011 ORR of 32% vs IC of 13%) and a trend of improvement in overall survival and PFS was demonstrated for the CDX-011 arm (CDX-011 median survival of 10.0 months vs IC of 5.7 months; p=0.18); (CDX-011 median PFS of 2.7 months vs IC of 1.5 months; p=0.14). For the overall study population, response rates, overall survival and progression free survival after treatment with CDX-011 suggested anti-tumor activity consistent with the standard of care. Patients receiving IC alone who crossed over to receive CDX-011 upon disease progression appeared to represent the better outcomes in the control arm, with a median survival of 12.5 months, as compared to those who did not cross over, with a median of 5.4 months.
"CDX-011 is eliciting impressive response rates in these patients with
heavily-pretreated metastatic disease, where physicians typically have
little expectation of clinical response. Most importantly, these
responses appear to translate into a survival benefit in the patients
where we would expect CDX-011 to work best, the targeted patient
populations with high levels of GPNMB on the tumor cell surface," said
Final Study Results:
A total of 122 patients were treated on the study, with 81 patients randomized to the CDX-011 arm and 41 patients to the IC single-agent chemotherapy arm, of which 15 later crossed over to receive CDX-011. In total, 81 CDX-011 patients (including cross overs) and 36 IC patients had on-study radiographic assessments and were evaluable for response. Nearly all patients had Stage IV, or metastatic, disease. Patients on the CDX-011 arm received a median of six prior courses of therapy and patients on the IC arm received a median of five prior courses of therapy. Adverse events prominent with the CDX-011 arm included rash and peripheral neuropathy, while hematologic toxicity was more frequent and severe in the IC arm. The Phase 2b EMERGE study required patients' tissue to have at least 5% of cells expressing GPNMB at entry and, based on this low threshold, 99% of screened patients were eligible for entry allowing for a specific focus on expression pattern subgroups. High GPNMB expression is defined as ≥25% of tumor epithelial cells expressing GPNMB by IHC.
Phase 2b EMERGE Final Survival Results: Survival Benefit of CDX-011 is Greatest in Patients with Triple Negative Disease that Highly Expresses (≥25%) GPNMB and All Patients with High GPNMB Expression* | ||||||||||||||||
All Patients |
Triple Negative |
High GPNMB |
Triple Negative and |
|||||||||||||
CDX-011 | IC | CDX-011 | IC | CDX-011 | IC | CDX-011 | IC | |||||||||
Median PFS (months) | 2.1 | 2.0 | 2.3 | 1.6 | 2.7 | 1.5 | 3.0 | 1.5 | ||||||||
p=0.38 |
p=0.43 |
p=0.14 |
p=0.008 |
|||||||||||||
Median OS (months) | 7.5 | 7.4 | 6.9 | 6.5 | 10.0 | 5.7 | 10.0 | 5.5 | ||||||||
p=0.24 |
p=0.30 |
p=0.18 |
p=0.003 |
*Analyses include all treated patients. Patients who initially received Investigator's Choice (IC) and subsequently crossed over to receive CDX-011 (n=15) are included in the PFS analysis for each treatment. These patients, with a median OS of 12.5 months (range 4.4 to 21.0 months), are assigned to the IC arm only for OS analysis.
Phase 2b EMERGE Final Overall Response Results: Activity of CDX-011 is Greatest in Patients with Triple Negative Disease that Highly Expresses (≥25%) GPNMB and All Patients with High GPNMB Expression* | ||||||||||||||||
All Patients | Triple Negative |
High GPNMB |
Triple Negative and |
|||||||||||||
CDX-011
(n=81) |
IC
(n=36) |
CDX-011
(n=27) |
IC
(n=9) |
CDX-011
(n=25) |
IC
(n=8) |
CDX-011
(n=12) |
IC
(n=4) |
|||||||||
% Response (% Confirmed) |
16 (10) | 14 (8) | 19 (7) | 0 | 32 (16) | 13 (13) | 33 (8) | 0 | ||||||||
% Disease Control Rate | 57 | 53 | 67 | 33 | 64 | 38 | 75 | 25 |
*Responses per RECIST 1.1; IC = Investigator's Choice; CDX-011 arm includes 15 patients who crossed over to receive CDX-011 treatment after progression on IC. Analysis of best response excludes patients who discontinued from study without evaluable post-baseline radiographic imaging (n=16 for CDX-011 arm; n=5 for IC arm).
About CDX-011:
CDX-011 (glembatumumab vedotin) is an antibody-drug conjugate (ADC) that consists of a fully-human monoclonal antibody, CR011, linked to a potent cell-killing drug, monomethyl-auristatin E (MMAE). The ADC technology, comprised of MMAE and a stable linker system for attaching it to CR011, was licensed from Seattle Genetics, Inc. The ADC is designed to be stable in the bloodstream. Following intravenous administration, CDX-011 targets and binds to GPNMB, a specific protein that is expressed in breast cancer and other tumor types which promotes the migration, invasion and metastasis of breast cancer. Upon internalization into the targeted cell, CDX-011 is designed to release MMAE from CR011 to produce a cell-killing effect. CDX-011 has been shown to be well tolerated and active, with observed objective responses in two positive Phase 1/2 trials in metastatic breast cancer and advanced melanoma. In May 2010, the U.S. Food and Drug Administration (FDA) granted Fast Track designation to Celldex's CDX-011 for the treatment of advanced, refractory/resistant GPNMB-expressing breast cancer.
About
Safe Harbor Statement Under the Private Securities Litigation
Reform Act of 1995: This release contains "forward-looking
statements" made pursuant to the safe harbor provisions of the Private
Securities Litigation Reform Act of 1995, including those related to the
Company's strategic focus and the future development and
commercialization of CDX-011 or any of our other drug candidates,
including rindopepimut (CDX-110), CDX-1135 (formerly TP10), CDX-1401,
CDX-1127, CDX-301, Belinostat and any future action we or the
All forward-looking statements are expressly qualified in their entirety by this cautionary notice. You are cautioned not to place undue reliance on any forward-looking statements, which speak only as of the date of this release. We have no obligation, and expressly disclaim any obligation, to update, revise or correct any of the forward-looking statements, whether as a result of new information, future events or otherwise.
Vice
President of IR & Corp Comm
scavanaugh@celldextherapeutics.com
or
For
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