Tokai Pharmaceuticals, Inc. TKAI today announced updated interim
results from its ongoing ARMOR2 Phase 2 clinical trial of galeterone in
castration-resistant prostate cancer (CRPC) patients. These interim results
from the trial support the potential of galeterone to treat CRPC expressing
androgen receptor (AR) splice variants, including AR-V7. The presence of AR
C-terminal loss generally, and AR-V7 specifically, has been linked to poor
responsiveness to hormonal agents commonly used to treat CRPC.
The data were presented today at the EORTC-NCI-AACR Symposium on Molecular
Targets and Cancer Therapeutics in an oral presentation titled “Activity of
Galeterone in Castrate-Resistant Prostate Cancer (CRPC) with C-Terminal AR
Loss: Results from ARMOR2” by Mary-Ellen Taplin, M.D., Associate Professor of
Medicine, Director of Genitourinary Clinical Research, Dana-Farber Cancer
Institute, Harvard Medical School, and co-principal investigator of ARMOR2.
“Recent data have shown that the AR-V7 splice variant of the androgen receptor
can be a predictor of resistance to treatment with enzalutamide and
abiraterone,” said Dr. Taplin. “We believe AR-V7 and other related variants
are a mechanism of resistance in this disease and patients who have them may
have a poorer prognosis.”
Results Support Galeterone Potential in the treatment of Patients with
C-Terminal Loss
In Part 2 of ARMOR2, the company is characterizing circulating tumor cells for
the presence of AR C-terminal loss. As previously reported, seven
treatment-naïve CRPC patients have been identified as having C-terminal loss
in a retrospective subset analysis; six of these patients had maximal
reductions in PSA levels of at least 50%. The seventh patient, who did not
show any PSA reduction, discontinued therapy due to an adverse event unrelated
to galeterone after approximately six weeks in the trial and did not receive
the full 12 week treatment regimen. As of October 14, 2014, the data cutoff
for the presentation, the median time to PSA progression among the seven
patients is 7.3 months, as defined by the Prostate Cancer Working Group 2
(PCWG2) criteria.
Of the six responders with AR C-terminal loss, four elected to continue into
an optional extension phase of the trial following the initial 12 week
treatment period. As of October 14, 2014, the time on treatment for these
patients in the extension phase ranged from 155 days to more than 334 days.
“In the subset of seven patients who had circulating tumor cells with a higher
ratio of N-terminal compared to C-terminal androgen receptors and so were
likely to have the AR-V7 variant, six had favorable PSA responses to
galeterone. This suggests that the presence of AR-V7 in circulating tumor
cells does not preclude response to galeterone as has been shown to be the
case for abiraterone and enzalutamide in independent clinical studies of those
compounds,” Dr. Taplin said.
Based on the results demonstrated in ARMOR2 in patients with AR C-terminal
loss and positive preclinical data in multiple AR-V7 models, the company
expects to initiate ARMOR3-SV, an open-label Phase 3 registrational trial in
the first half of 2015. In ARMOR3-SV, patients will be screened and those
testing positive for AR-V7 will then be randomized to receive either
galeterone or enzalutamide. The trial will have a primary endpoint of
radiographic progression-free survival, with secondary endpoints that include
overall survival, skeletal-related events and time to cytotoxic therapy.
“The continued encouraging efficacy and tolerability from ARMOR2 demonstrate
that galeterone has the potential to become an important treatment option for
CRPC patients, including AR-V7 patients with high unmet need,” said Jodie
Morrison, President and Chief Executive Officer of Tokai Pharmaceuticals. “We
remain on track to initiate ARMOR3-SV, the first biomarker-based
registrational trial of its kind in prostate cancer, in the first half of 2015
with top line results targeted for the end of 2016.”
Clinically Meaningful PSA Reductions, Favorable Safety Profile in CRPC
Patients
ARMOR2 is a two-part Phase 2 study designed to confirm the dose of galeterone
and demonstrate safety and efficacy in treatment-naïve metastatic and
non-metastatic CRPC patients.
The interim results presented include data collected as of October 14, 2014,
on 107 patients in Part 1 and Part 2 of the trial who were treated with
galeterone at a daily oral dose of 2550 mg. Consistent with a prior interim
analysis, among 39 treatment naïve metastatic CRPC patients, 85% achieved a
maximal reduction in PSA levels of at least 30% (PSA30) and 77% achieved a
maximal reduction in PSA levels of at least 50% (PSA50). Among 60 combined
non-metastatic and metastatic treatment naïve CRPC patients, 83% achieved a
PSA30 and 70% achieved a PSA50.
Galeterone was well tolerated, with approximately 90% of reported adverse
events (AEs) classified as Grade 1 or 2.
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