Porter v. Tap Pharmaceutical, et al

Filing 588

Judge Richard G. Stearns: ORDER entered acknowledging receipt and review of A. David Mazzone Programmatic Report #8. (Zierk, Marsha)

UNITED STATES DISTRICT COURT
DISTRICT OF MASSACHUSETTS
M.D.L. NO. 1430
CIVIL ACTION NO. 01-10861
IN RE LUPRON® MARKETING AND
SALES PRACTICES LITIGATION
MEMORANDUM ACKNOWLEDGING THE RECEIPT
AND REVIEW OF THE
A. DAVID MAZZONE PROGRAMMATIC REPORT #8
March 31, 2015
STEARNS, DJ.
On March 30, 2015, Dr. Philip Kantoff of the Dana-Farber/Harvard
Cancer Center (DF/HCC), the principal investigator for the A. David
Mazzone

Research

Awards

Program

(Program),

and

co-principal

investigator, Dr. Jonathan Simon, President of the Prostate Cancer
Foundation (PCF), submitted the eighth in a series of Program Reports.
This Report covers the period from July 1, 2014, to December 31, 2014.
Prior to the reporting period, in 2014, the court authorized the
distribution of the remaining $160,000 of Program funds. DF/HCC issued
a special 2014 Request for Applications (RFA) to solicit grant proposals in
the areas of Community Outreach and Disparities Research. With the
additional money, the Program was able to fund two new Disparities
Research grants of $90,000 and $50,000.
1

The Program allocated the

remaining $20,000 to Student Training through the DF/HCC Cure
Program. PCF also awarded its final $500,000 matching grant during the
same period.
Dr. Kantoff and Dr. Simon report that the special RFA grants were
awarded through the screening and evaluation process established in
previous years for communicating, collecting, reviewing, and selecting
projects.

The DF/HCC RFAs were publicized in venues relevant to

Community Outreach and Disparities Research. Proposals were vetted by
peer reviewers with expertise in the field. A merit score for each proposal
was determined based on the published review criteria after extensive
discussion by the peer committee, which made the final recommendations
to Dr. Kantoff.
The first grant ($50,000 for two years) was awarded to principal
investigator Zoltan Szallasi, MD, Children’s Hospital, Boston; co-principal
investigator, Matthew Freedman, MD, DFCI; and collaborator Mark
Pomerantz, MD, DFCI, for the research proposal:

Whole genome

sequencing based identification of clinically relevant genomic aberrations
specific to prostate cancer cases in African Americans.

In their

application, the investigators noted that while the medical community has
been long aware that prostate cancer disproportionately affects African
2

Americans (who are diagnosed at an earlier age, progress more quickly, and
are three times more likely to die of the disease), no systematic study has
ever compared the cancerous genome between African American and
European American prostate cancer patients. The investigators will seek to
identify somatic genomic aberrations that are predominantly present or
absent in prostate cancers afflicting African Americans. To do so, they will
analyze the cancer genome of twenty-seven African Americans and one
hundred Caucasian patients to determine structural, copy number, and
mutational variations that are predominantly present in one as opposed to
the other group. Any genomic aberrations will be validated in an
independent cohort and correlated with the clinical course of disease. The
results will enable diagnosis and more aggressive treatments, and may also
provide therapeutic targets.
The second grant ($90,000 for two years) was awarded to principal
investigator Mark Preston MD, MPH, Brigham and Women’s Hospital and
collaborator Lorelei Mucci, ScD, Harvard School of Public Health for the
proposal: Do Baseline Prostate Specific Antigen (PSA) Levels Predict
Advanced Prostate Cancer in African-American Men? The investigators
acknowledge that while prostate specific antigen (PSA) screening has been
shown to reduce mortality from prostate cancer, the screening is
3

controversial because of the risk of over-diagnosis and over-treatment. The
investigators note that no study to date has examined the predictive ability
of PSA among African-American men, a group with a substantially higher
prostate cancer incidence and mortality than white men.

To enhance

screening strategies, the investigators propose leveraging the Southern
Community Cohort Study (SCCS), a well-established, prospective cohort
that includes a high-proportion of African-American men, to determine the
predictive ability of baseline PSA testing in African-American men during
midlife.
As anticipated in the last report, the PCF issued an RFA for its final
$500,000 Mazzone Special Challenge Award. It selected as grantees and
principal investigators David Baltimore, Ph.D., President Emeritus, and
Robert Andrews Millikan Professor of Biology at the California Institute of
Technology (CIT); together with collaborators Owen N. Witte, M.D.,
University of California, Los Angeles (UCLA), professor of microbiology,
immunology, and molecular genetics; Lili Yang, Ph.D., UCLA assistant
professor of microbiology, immunology, and molecular genetics; and
Michael T. Bethune, Ph.D., senior postdoctoral fellow in biology at CIT.
Their study - T Cell Receptor Gene Therapy for Treatment of Lethal
Prostate Cancer – will seek to devise a new strategy for discovering
4

antigenic targets of T cell immunity. By cloning T cell receptors (TCRs) that
are enriched among prostate cancer-reactive T cells (that is, tumorinfiltrating T cells or T cells that expand when co-cultured with a prostate
cancer cell line), the investigators hope to identify TCRs that recognize the
most immunogenic prostate tumor antigens.

They will then construct

soluble reagents from these TCRs and use them to select cognate antigens
from a library of HLA-A2-bound peptides displayed on the surface of yeast.
This represents a fundamentally new approach to cancer antigen discovery
that is expected to have broad applicability to other T cell-driven immune
responses for which antigenic targets are unknown. The investigators will
seek to promote the use of TCR gene therapy for prostate cancer, and to use
a competition-based assay to select the prostate-reactive TCRs that are
most highly expressed upon T cell transduction, thereby maximizing their
potential for clinical application. They hope to provide proof-of-concept
studies showing that the primary danger of TCR gene therapy – lethal graftvs-host disease resulting from TCR mispairing – can be addressed by a
novel and general strategy of swapping domains between the TCR α and β
chains. This should streamline the development of new TCR gene therapies
by establishing measures to improve the safety and efficacy of TCR
candidates.

By comparing TCR gene therapies in their efficacy, the
5

investigators will seek to categorize newly discovered antigens as
therapeutic targets for SCPC and castration-resistant adenocarcinoma, or
both. Finally, they will investigate the extent to which vaccination with
these novel antigenic targets potentiates TCR gene therapy in vivo. All
tumor models, antigenic vaccines, and TCRs tested will be of human origin.
The court firmly believes these three innovative studies will make an
invaluable contribution to the goals of the Mazzone Program as it nears its
conclusion. The court looks forward to receipt of the September 30, 2015
Annual Progress Report.
/s/ Richard G. Steams
___________________
United States District Judge

6