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Annals of Oncology
(visceral and nodes). The most common Grade 3/4 adverse events (AEs) were
neutropenia (64.5%, 20 Pts) leukopenia (45.2%, 14 Pts), and febrile neutropenia
(9.7%, 3 Pts). G3/4 diarrhoea was reported 3.2%, 1 pt. Pain response was 64.3%.
PSA response 6 cycles (32 Pts)
decline ≥50%
PSA response by Gleason (decline >50%)
53%
GS 4-6 ( 9 Pts) 44%
GS 7 (10 Pts) 60%
GS 8-10 (13 Pts)
PSA response by previous D regimen
54%
1 (17 Pts) 12 (71%)
>1 (15 Pts) 5 (33%)
Tumor Response (RECIST) 22 Pts
PR + SD 19 (86.4%)
PD 3 (13.6%)
Conclusions: Our results indicate a high activity of cabazitaxel in terms of PSA,
tumor and pain responses in all subgroups of pts analysed; cabazitaxel shows globally
a clinically manageable safety profile in daily clinical practice.
Disclosure: All authors have declared no conflicts of interest.
963TiP PHASE I TRIAL OF ASG-5ME IN METASTATIC CASTRATION
RESISTANT PROSTATE CANCER (CRPC)
M. Morris 1 , J. Bruce 2 , L. Reyno 3 , B. Anand 3 , A. Hartford 3 , K. Jelaca-Maxwell 3 ,
J. Lackey 3 , M. Eisenberger 4
1 Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, UNITED
STATES OF AMERICA, 2 Medicine, University of Wisconsin Center for Health
Sciences Medical School UW Carbone Cancer Center, Madison, WI, UNITED
STATES OF AMERICA, 3 Development, Agensys, Santa Monica, CA, UNITED
STATES OF AMERICA, 4 Medicine, Sidney Kimmel Comprehensive Cancer
Center at Johns Hopkins Medical Center, Baltimore, MD, UNITED STATES OF
AMERICA
Background: SLC44A4 is a 710 amino acid protein expressed on prostate, pancreas
and other cancers. SLC44A4 is found in 95% of primary prostate tumors (75%
express moderate to high levels). ASG-5ME is an antibody drug conjugate (ADC)
comprised of a fully human antibody against SLC44A4, conjugated to the
microtubule-disrupting agent monomethyl auristatin E. ASG-5ME has
dose-dependent cytotoxic effects in vitro and significant anti-tumor activity in
xenograft models. We report results of a phase I study of ASG-5ME for CRPC,
conducted by the Prostate Cancer Clinical Trials Consortium.
Methods: Patients (pts) had progressive metastatic CRPC. Prior chemotherapy was
allowed. Treatment cohorts were 0.3, 0.6, 1.2, 1.8, 2.4, 2.7 and 3.0 mg/kg. ASG-5ME
was given IV q3 weeks. Safety, pharmacokinetic properties, anti-tumor effects,
circulating tumor cell (CTC) enumeration, and CTC molecular profiles were assessed.
Pts were treated until disease progression or unacceptable toxicity. Dose limiting
toxicity (DLT) was defined by cycle 1 toxicity.
Results: 26 pts have been treated (3, 3, 3, 3, 6, 6, and 2 pts per respective cohort).
Mean age was 69.5 (range 56-87), median Gleason score 8 (6-10), mean baseline PSA
82.25 (4.4-1987). Pts received a mean of 3.8 doses (1-12). A DLT occurred at 2.7 mg/
kg: Grade (Gr) 4 neutropenia, Gr 3 constipation and diarrhea. 2 DLTs occurred at 3
mg/kg: one with Gr 3 troponin elevation and the second with Gr 3 maculopapular
rash, hypoxia, constipation, and Gr 4 neutropenia. Common Gr 1 and 2 adverse
events included fatigue, anorexia, peripheral neuropathy, dyspnea and nausea. Gr 3
events included: fatigue (2 pts), peripheral neuropathy (1), dyspnea (1) and nausea
(1). Serum concentrations of ASG-5ME decreased multi-exponentially and the
exposure was dose-proportional. The half-life of the ADC was 7.01 days
(range-3.93-15.9, n = 17) after the first dose and 11.2 days (range-7.75-19.1 days, n =
10) after the last dose. PSA declines of >50% were seen in 3/8 pts treated in the last 3
cohorts and one >50% decrease in retroperitoneal nodes.
Conclusions: The maximum tolerated dose (MTD) was exceeded at 3 mg/kg. The
drug appears to have anti-cancer activity above 2.4 mg/kg.
Disclosure: L. Reyno: The author is the CMO and Sr Vice President of Agensys, Inc,
B. Anand: The author is a director of Agensys, IncA. Hartford: The author is a
director of Agensys, Inc, K. Jelaca-Maxwell: The author is a paid safety consultant of
Agensys, Inc, J. Lackey: The author is a director of Agensys, Inc. All other authors
have declared no conflicts of interest.
964TiP ARN-509 IN MEN WITH METASTATIC
CASTRATION-RESISTANT PROSTATE CANCER (CRPC)
D. Rathkopf 1 , E.S. Antonarakis 2 , N.D. Shore 3 , R. Tutrone 4 , J. Alumkal 5 ,
C.J. Ryan 6 , M. Saleh 7 , R. Hauke 8 , E. Chow-Maneval 9 , H.I. Scher 1
1 Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, UNITED
STATES OF AMERICA, 2 Sidney Kimmel Comprehensive Cancer Center, Johns
Hopkins University, Baltimore, MD, UNITED STATES OF AMERICA, 3 Urology,
Carolina Urologic Research Center, Myrtle Beach, SC, UNITED STATES OF
AMERICA, 4 Urology, Chesapeake Urology Research Associates, Baltimore, MD,
UNITED STATES OF AMERICA, 5 Medicine, Oregon Health & Science University
Knight Cancer Institute, Portland, OR, UNITED STATES OF AMERICA, 6 Ucsf
Helen Diller Family Comprehensive Cancer Center, University of California,
San Francisco, San Francisco, CA, UNITED STATES OF AMERICA, 7 Medicine,
Georgia Cancer Specialists, Atlanta, GA, UNITED STATES OF AMERICA,
8 Medicine, Nebraska Cancer Specialists, Omaha, NE, UNITED STATES OF
AMERICA, 9 Clinical Development, Aragon Pharmaceuticals, San Diego, CA,
UNITED STATES OF AMERICA
Background: ARN-509 is a novel second-generation anti-androgen that binds
directly to the ligand-binding domain of the androgen receptor, impairing nuclear
translocation and DNA binding. The Phase II portion of a multicenter Phase I/II
study is evaluating the activity of ARN-509 in 3 distinct patient populations of men
with CRPC: 1) non-metastatic treatment-naïve CRPC; 2) mCRPC treatment-naïve
(tx-naïve); and 3) mCRPC abiraterone acetate pre-treated (AA). Preliminary results
for the 2 cohorts of patients with metastatic CRPC are presented here.
Methods: All patients had metastatic CRPC with progressive disease based on rising
PSA and/or imaging. No prior chemotherapy for metastatic prostate cancer was
allowed. Patients on the AA pre-treated cohort had to have been treated with AA for
at least 6 months. All patients received ARN-509 at the recommended Phase II dose
of 240 mg/day (Rathkopf et al, GU ASCO 2012). The primary endpoint was PSA
response rate at 12 weeks according to the Prostate Cancer Working Group 2 Criteria
in each of the treatment groups. Secondary endpoints included safety, time to PSA
progression and objective response rates. PSA assessments were collected every 4
weeks and tumor imaging was performed every 16 weeks.
Results: To date, 32 patients have been enrolled: 25 on the tx-naïve and 7 on the
post-AA cohorts, respectively. The combined median age was 67 (range 51-91) and at
baseline, patients presented with ECOG performance status 0 (55%), Gleason Score 8-10
(54%), and median PSA of 14.7 (tx-naïve) and 69.6 (post-AA) ng/mL. All patients
received prior treatment with a LHRH analog with or without a first-generation
anti-androgen. At a median treatment duration of 16 weeks, 4 patients discontinued the
study due to disease progression, 2 in each cohort. The most common treatment-related
adverse events (AE) were abdominal pain (36%), diarrhea (19%), nausea (16%) and
fatigue (10%). There was only 1 treatment-related Grade 3 AE of abdominal pain. At 12
weeks, the PSA response was 91% (tx-naïve) and 60% (post-AA), respectively.
Conclusion: In men with CRPC, ARN-509 is safe and well tolerated with promising
preliminary activity in metastatic, chemo-naïve patients both before and after
treatment with abiraterone.
Disclosure: E. Chow-Maneval: Dr. Chow Maneval is an employee of Aragon and
holds stock in the company. All other authors have declared no conflicts of interest.
965TiP A PHASE II STUDY (PERSEUS) OF TWO DOSES OF EMD
525797 (DI17E6) IN PATIENTS (PTS) WITH ASYMPTOMATIC
OR MILDLY SYMPTOMATIC METASTATIC
CASTRATE-RESISTANT PROSTATE CANCER (MCRPC)
K. Miller 1,* , M. Hussain 2,* , G. Mordenti 3 , H. Lannert 4
1 Charité, Department of Urology, Berlin, GERMANY, 2 University of Michigan,
Comprehensive Cancer Center, Ann Arbor, MI, UNITED STATES OF AMERICA,
3 Merck Serono S.A., Global Biostatistics, Geneva, SWITZERLAND, 4 Merck
KGaA, Global Clinical Development Unit Oncology, Darmstadt, GERMANY, * on
behalf of the PERSEUS Study Group
Purpose: Expression and function of αv-integrins are deregulated in prostate cancer,
and αv-integrins are thought to play an important role in prostate cancer metastasis.
EMD 525797 (DI17E6) is a humanized monoclonal IgG2 antibody specifically
directed against αv integrin receptors (αvß1, αvß3, αvß5, αvß6, and αvß8). It has
been shown to target tumor cells, the tumor’s environment (e.g. osteoclasts and
osteoblasts), as well as angiogenic blood vessels. Previous studies with EMD 525797
have shown a favorable tolerability profile in healthy volunteers and in mCRPC pts.
A phase II trial is investigating the anticancer activity of 2 dose levels of EMD
525797 in asymptomatic or mildly symptomatic mCRPC pts.
Methods: Adult pts with CRPC who show radiologic progression of bone lesions
with/without soft tissue lesions within 28 days prior to randomization are eligible for
inclusion. Exclusion criteria are: acute pathologic fracture, spinal cord compression,
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds400 | ix317