Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 69
9
Examples of Collaborations
Relevant to Cancer
During the course of the workshop, participants cited several exam -
ples of successful collaborations in the development of investigational
combination cancer therapies, including preclinical and clinical collabora-
tions between two drug companies, as well as clinical trial collaborations
involving academic institutions and multiple companies, such as I-SPY 2
TRIAL and BATTLE 1 and 2, and some research funded by Stand Up To
Cancer, the latter of which encompasses both preclinical and clinical drug
development.
A few preclinical collaborations between two drug companies were
cited. Dr. Bachman noted that GSK and Novartis are collaborating in the
development of a cancer therapy that combines GSK’s MEK inhibitor with
Novartis’s PI3K inhibitor. Although GSK had its own PI3K inhibitor in
the pipeline, the GSK inhibitor had different properties from the Novartis
P13K inhibitor that made the collaboration worth pursuing, Dr. Bachman
noted. “Rather than just us focusing on our own inhibitor, we talked to
Novartis. Similarly Genentech and Roche are collaborating on the pre-
clinical development of a combination treatment that targets both P13K
and MEK, and AstraZeneca is collaborating with Merck in the preclinical
development of a combination that targets PI3K and ATK,” Dr. Engelman
pointed out. “It’s very exciting that these companies, when they see an
idea that they think is good, are willing to go through the painful process
of teaming up to codevelop molecules. What’s very telling here is that
these companies are codeveloping molecules that aren’t approved—they
69
OCR for page 70
70 COLLABORATIONS TO DEVELOP COMBINATION CANCER THERAPIES
are both being developed when neither one is really even that close to an
FDA approval,” he said.
Dr. Canetta noted additional clinical collaborations between two
pharmaceutical companies, each contributing their own investigational
drug. These collaborations included Bristol-Myers Squibb and Roche in
the clinical testing of a combination for melanoma, and Bristol-Myers
Squibb and Genentech in the clinical testing of a combination for colorec -
tal cancer, done under the auspices of CTEP. These trials show that it is
possible to do combination trials with experimental agents and address
concerns about intellectual property and regulatory issues. “All that it
takes is recognition of the unmet medical need and willingness to cooper-
ate,” he said.
Even more complex, multi-industry collaborations have been forged,
as exemplified by the I-SPY 2 TRIAL and BATTLE 1 and 2 trials (see
Appendix A). Mr. David Wholley, director of the Biomarkers Consortium,
said that having the Foundation for the National Institutes of Health
(FNIH) act as a trusted third party was key to forging the 19 agreements
involved with the I-SPY 2 TRIAL. FNIH acts as the holder of the IND and
as the manager of the IP rights that stem from the trials. Mr. Wholley said
an outside legal counsel who has worked with the I-SPY 2 TRIAL and is
skilled in the area of IP licensing said she was amazed that FNIH was able
to garner these agreements, and noted it would not have been possible if
FNIH was not a trusted third party and a nonprofit organization.
Dr. Herbst noted that the four companies sponsoring the BATTLE 2
trial have been flexible in the choice of agents the investigators have used,
even as this choice evolved when more knowledge on targeted therapies
emerged. “The company allowed us to work with drugs from other com-
panies and bring other collaborators in. We have a good example where
academia and industry really worked well together,” Dr. Herbst said.
The PI3K team funded by Stand Up To Cancer has invested $500,000
to purchase 50–100 gram quantities of 10 investigational drugs that
recently entered Phase II clinical trials and that were of interest to them for
combination therapies. The team’s strategy is to test these drugs as single
agents and in combinations, and to immediately inform the companies
that make these drugs if they observe efficacy in any of our mouse mod-
els as indicated by tumor shrinkage. They then work with the companies
that make the drugs to facilitate their biomarker-driven combination trials
(sometimes involving two companies).
Agents used for testing are obtained from both industry and CTEP,
and accrual is facilitated by interactions with the Translational Breast
Cancer Research Consortium, the Gynecologic Oncology Group, and
other individual centers, Dr. Cantley noted. The PI3K team also lever-
OCR for page 71
71
EXAMPLES OF COLLABORATIONS RELEVANT TO CANCER
ages complementary trials that were already in the works when the PI3K
team formed.
“Collaborations with industry have offset many of our costs,” Dr.
Cantley pointed out. But he added that in general, it takes about a year
to acquire a material transfer agreement with a company in order to use
their investigational agent to test in their animal models, and most agree -
ments stipulate the agent cannot be combined with any other drug. That
has not deterred researchers on the P13K team from combining agents in
their tests, however, Dr. Cantley said. “We always tell the company we’re
doing it. They may or may not tell their lawyers we’re doing it. But we
do it, and if we get a result that looks exciting, we come back and tell
them and I’ve yet to have anyone complain,” Dr. Cantley said. Instead,
companies have been open to discussions on how to collaborate with each
other to further test combinations where the agents come from different
companies, according to Dr. Cantley. In two such cases those discussions
have led to collaborative combination trials. “The barriers are not that
high if the data are really convincing,” Dr. Cantley said.
OCR for page 72
