Annual Meeting Proceedings Part 1 - American Society of Clinical ...

326s Genitourinary Cancer
TPS4698^ General Poster Session (Board #17A), Sun, 8:00 AM-12:00 PM
TERRAIN: A randomized, double-blind, phase II study comparing MDV3100
with bicalutamide (Bic) in men with metastatic castrate-resistant prostate
cancer (CRPC). Presenting Author: Edwina S. Baskin-Bey, Astellas Pharma
Europe, Ltd., Staines, United Kingdom
Background: MDV3100 is a novel androgen receptor (AR) signaling inhibitor
(ARSI) in clinical development for treatment of prostate cancer (PCa).
Compared with Bic in nonclinical CRPC models, MDV3100 showed higher
affinity AR binding, inhibited nuclear translocation and AR-DNA binding,
showed no evidence of AR agonism, and caused tumor regression in
Bic-resistant xenografts. MDV3100 has shown antitumor activity in men
with advanced PCa. We present the study design of a trial comparing
MDV3100 and Bic in men with progressive metastatic PCa. Methods:
Multinational study (Table) with planned enrollment of 370 patients
(randomized 1:1 to MDV3100 160 mg/d or Bic 50 mg/d). Inclusion criteria
include metastatic (�2 bone lesions or soft tissue disease at screening)
progressive CRPC (�3 rising prostate-specific antigen [PSA] levels or new
bone/soft tissue disease), ongoing stable gonadotropin-releasing hormone
(GnRH) analog therapy or surgical castration (serum testosterone �50
ng/dL), Eastern Cooperative Oncology Group performance status 0–1, and
life expectancy �1 year. Exclusion criteria include previous chemotherapy,
current/prior antiandrogens (except if administered for �12 wk and
discontinued no less than 6 mo before study). Patients will be stratified by
time of bilateral orchiectomy or GnRH analog initiation (before/after
diagnosis of metastases) and will receive treatment until occurrence of
radiographic progression/skeletal-related event, start of new antineoplastic
therapy, or development of an adverse event requiring discontinuation.
Results: The primary endpoint is progression-free survival; secondary
endpoints are safety, PSA response, and time to PSA progression. Exploratory
endpoints include circulating tumor cell conversion rate and quality of
life. Patients are currently enrolling. Conclusions: This ongoing, head-tohead,
phase II trial is the first to prospectively assess whether MDV3100
can provide improved antitumor effects vs Bic in men with metastatic
CRPC.
Country Sites, n
Canada 4
US-East 12
US-Midwest 13
US-South 11
US-West 10
France 9
Germany 6
Romania 3
UK 5
Belgium 5
TPS4700 General Poster Session (Board #17C), Sun, 8:00 AM-12:00 PM
Targeting castration resistant prostate cancer (CRPC) with autologous
PSMA-directed CAR� T cells. Presenting Author: Susan F. Slovin, Sidney
Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-
Kettering Cancer Center, New York, NY
Background: Based on our preclinical animal models, we initiated a phase I
dose-escalating study to assess safety, dose requirement and targeting
efficiency of genetically directed autologous human T cells targeted to
Prostate Specific Membrane Antigen (PSMA). Our approach is based on the
infusion of autologous PSMA-targeted T cells utilizing the P28z second
generation chimeric antigen receptor (CAR) in patients (pts) with metastatic
CRPC, following iv cyclophosphamide (Cy) (trial NCT01140373).
For safety, the herpes simplex virus-1 thymidine kinase (hsvtk) gene is
co-expressed with the P28z receptor, and renders T cells sensitive to
ganciclovir for immediate T cell elimination if needed. The expression of
hsvtk enables PET imaging using radiolabeled FIAU to localize adoptively
transferred T cells. The aims of the trial are to assess: (1) safety of
PSMA-targeted T cells; (2) biologic and anti-tumor effects; (3) T cell
persistence at tumor site; and (4) immune response. Methods: Autologous T
cells are activated from a leukapheresis product using anti-CD3/CD28
Dynabeads. Release criteria include mean vector copy number by Q-PCR
and vector identity by Southern blot, absence of Replication Competent
Retrovirus and residual Dynabeads. Pts will be treated at 3 dose levels from
107 to 108 CAR� T cells/kg. Four patients have been enrolled; 3 have been
treated with 300mg/m2 of Cy one day before infusion of 107 CAR� T
cells/kg. Pts underwent baseline and post treatment CT, bone and PET
scans. Pts are followed weekly, then monthly with blood work including
immune and vector sequence monitoring. Results: The first 3 pts within the
first cohort were successfully treated without toxicity. Two had stable
disease for greater than 6 months with the third patient having disease
progression. There were no acute adverse events. Conclusion: We have
established an ex vivo transduction, expansion and therapeutic protocol for
the generation and testing of safe, clinical-grade, PSMA targeted T cells.
Pts enrolled at the next dose level of 3x107CAR� T cells/kg will be
assessed as described and by imaging the transduced T cell population
using 18F-FIAU as a radiotracer. The data pertaining to the planned T cell
imaging will be presented as well.
TPS4699 General Poster Session (Board #17B), Sun, 8:00 AM-12:00 PM
Prospect: A randomized, double-blind, phase III efficacy trial of PROST-
VAC. Presenting Author: Olga Bandman, BN ImmunoTherapeutics, Mountain
View, CA
Background: PROSTVAC is a candidate cancer vaccine comprised of two
recombinant poxviral vectors: vaccinia (V) and fowlpox (F), each with
insertions of four human genes: PSA and three costimulatory molecules
(TRICOM) - LFA-3, B7.1 and ICAM-1. This off the shelf vaccine demonstrated
a statistically significant overall survival (OS) benefit of 8.5 months
while displaying a favorable side effect profile in patients (pts) with
asymptomatic to minimally symptomatic prostate cancer (mCRPC) in a
randomized, placebo –controlled 122-pt Phase II trial. Data from this
Phase II trial supported the design of a Phase III protocol that will rigorously
test the hypothesis of OS benefit, as well as expand our understanding of
immune system response to cancer vaccines. Methods: 1200 pts will be
randomized in a double-blind fashion to three arms: PROSTVAC,
PROSTVAC�GM-CSF, or Placebo, at 1:1:1 ratio. A five-month treatment
regimen will include a priming vaccination with PROSTVAC-V, and six
booster vaccinations with PROSTVAC-F. Eligible pts will have asymptomatic
or minimally symptomatic mCRPC, and progression despite androgen
ablation and be chemotherapy-naïve. Pts with rapidly progressing disease
will be excluded, as well as pts with risk factors for developing vacciniaassociated
complications. The projected trial size is 400 pts per arm for at
least 85% power. Primary endpoint is OS. The final analyses will be
event-driven and will compare each active arm independently with placebo.
Pts will be followed for 12 months after the projected number of events in
each arm is realized. Secondary endpoint is proportion of event-free pts at 6
months compared to placebo. A number of exploratory endpoints are
planned, including immune response to immunizing antigen, non-vaccinecontained
prostate antigens, tumor-associated antigens; changes in baseline
biomarker levels and CTC levels, as well as characterization of T cell
subpopulations. The thorough immune monitoring program would provide
basis for future studies on the effects of cancer immunotherapy on immune
system and facilitate search for potential biomarkers of such effects. The
trial is currently open for enrollment. ClinicalTrials.gov registry number:
NCT00450463.
TPS4701 General Poster Session (Board #17D), Sun, 8:00 AM-12:00 PM
Randomized phase II clinical trial to assess MUC1 specific immune
response to L-BLP25 vaccine in addition to standard therapy in newly
diagnosed high-risk prostate cancer. Presenting Author: Nishith Singh,
Laboratory of Tumor Immunology and Biology and Medical Oncology
Branch, National Cancer Institute, Bethesda, MD
Background: In high-risk prostate cancer, radiation therapy (RT) � androgen
deprivation therapy (ADT) improve survival. Nonetheless, 10-year
disease specific mortality is about 25%. L-BLP25 is a cancer vaccine
containing the BLP25 lipopeptide that targets MUC1 tumor antigen. It may
enhance immune targeting of cells that express MUC1 (e.g. prostate
cancer). In murine models, RT synergizes with vaccine-induced anti-cancer
immunity (augments T-cell mediated cancer cytolysis, up-regulates cellular
Fas and co-stimulatory/adhesion molecules). ADT augments T-cell
trafficking to prostate. Immune response to combining the three (L-BLP25
� RT � ADT) is not known. The current trial intends to study this immune
response to L-BLP25 � RT � ADT and compare it to RT�ADT alone. Using
ELISPOT, endo-rectal MRI and serial prostate biopsies, this trial was
designed to correlate systemic immune response with changes in tumor
imaging and/or tumor microenvironment after treatment with L-BLP25.
This trial may provide insight into immune response biomarkers that are
most appropriate in this setting. Methods: A randomized (1:1), open-label,
phase II trial of 42 pts is planned. Eligibility: Adult males with newly
diagnosed high-risk prostate cancer (T3 or Gleason � 8 or seminal vesicle
involvement or N1 or PSA�20) and HLA-A2/A3 positivity (to allow for
ELISPOT analysis). The vaccine arm will receive RT � 2-year ADT �
L-BLP25. Standard arm will receive RT � 2-year ADT. L-BLP25 vaccine
schedule: biweekly X 5 starting with neo-adjuvant ADT, then 6 weekly X 4
starting with RT. A single 300mg/m2 cyclophosphamide infusion (decreases
suppressor T-cells) will be given 3 days before L-BLP25 to enhance
immune response in the vaccine arm. The impact of L-BLP25 � RT�ADT
on MUC-1-specific systemic immune response will be determined using
interval peripheral blood ELISPOT assays. Endo-rectal coil MRI will be
done before and after treatment to study prostate signal changes for
correlative and predictive analysis. MRI-UltraSound guided lesion-targeted
serial prostate biopsies will be obtained to assess immune response in
tumor microenvironment. Two pts have been enrolled.
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