Transcript Oncology Models – Jaime Modiano

CVM-Pharmacy Spring Symposium
What CVM has to Offer (Oncology)
(ACCR)
Jaime F. Modiano
The Animal Cancer Care and
Research Program (ACCR)
• Joint program of CVM and MCC
• Basic, translational, and clinical
research mission
• Educational and training mission
• Clinical service delivery mission
Onc Section Faculty and Research Interests
• Jaime Modiano – Professor
– Cancer biology, immunology, genetics
• Mike Henson – Associate Professor
– Translational therapy
• Fekadu Kassie – Assistant Professor
– Cancer chemoprevention
• Erin Dickerson – Assistant Professor
– Drug targeting and cancer metabolism
• Antonella Borgatti – Assistant Professor
– Translational therapy
• Daisuke Ito – Assistant Professor (6/1/13)
– Lymphoma biology
• Claire Cannon – Research Associate (Onc Fellow)
– Translational therapy
Other ACCR Faculty
•
•
•
•
•
•
•
•
Liz Pluhar and Vicki Wilke (CVM, Surgery)
Subree Subramanian (SOM - Surgery)
Aaron Sarver (MCC)
David Largaespada (MCDBG)
Khalil Ahmed (VA and SOM, LMP)
Jeff Miller (SOM, Medicine)
Dan Vallera (SOM, Radiology)
Many others
Research Opportunities
• > 1 million dogs are diagnosed and managed with
cancer in the U.S. each year
• Intact immune system
• Compressed life span
• Cancers are influenced by similar factors (e.g. age,
nutrition, gender, reproductive state, environmental
exposure)
www.canusgoatsmilk.com
Key Programs
• Brain cancer (Pluhar, Moertel)
• Sarcomas (Borgatti, Weigel, Largaespada, Spector, Wilke,
Sarver, Subramanian, Modiano, Dickerson, Clohisy, et. al.)
• Hematologic malignancies (Ito, Miller, Modiano, O’Brien,
Linden, Bachanova, Burns)
• Chemical carcinogenesis and prevention (Kassie)
• Etiology and cancer genetics (Modiano, Sarver,
Subramanian, Largaespada, O’Brien, Kassie)
• Therapeutic targeting and microRNAs (Subramanian,
Dickerson, Vallera, Ahmed, Kassie)
• Clinical trials (Borgatti, Henson, Cannon)
Resources
• Tissue bank
– >100 cell lines (mostly sarcomas) and
>1200 tumor samples with blood for germ
line DNA (e.g., T:N sequencing) with broad
geographic distribution
– Bank was developed as a joint effort with
collaborators at Broad and NCSU, and
supplemented from local patient samples
and from U of M clinical studies
Clinical Opportunities
• Studies originating locally (home
grown therapies)
• Studies originating from contracts or
collaborations (imported technology)
• Hypothesis testing and hypothesis
generating
Tumor Distribution at the CVM
All Admissions
Tumor Distribution at the CVM
New Diagnoses
- New Diagnoses
Clinical Oncology Studies at the CVM
Disease
Study
Description
Inclusion/exclusion
Lymphoma
(LSA)
Karyo-1
CRM1 inhibitor
Safety, dose-finding study
Dogs with lymphoma,
otherwise healthy
LSA
Karyo-2
CRM1 inhibitor
Efficacy study
LSA
MADGIC
LSA
Incentive
PI
Status
Fully funded
Borgatti
C
Dogs with naïve and
first relapsed
lymphoma, otherwise
healthy
Fully funded
Borgatti
A
Sample collection study
Discovery and characterization
of heritable and somatic
cancer mutations in Golden
Retrievers
Dogs with lymphoma
Biopsy samples and
blood samples
Modiano
A
LICKing
Lymphoma
PSC-833
Ablation of tumor initiating
cells, safety and efficacy study
with concurrent doxorubicin
chemotherapy
Dogs with lymphoma,
otherwise healthy
Study drug
$2,000 to owners
towards
chemotherapy
Modiano
C
LSA
Idarubicin
Prospective, open- label,
phase I
Dogs with measurable
lymphoma
Study costs
Husbands
C
LSA
Acupuncture
Efficacy of acupuncture in
alleviating chemotherapyinduced side effects
Concurrent doxorubicin
chemotherapy
Randomized, double-blinded
Dogs with lymphoma
Covers the cost of
acupuncture
Choi
P
Clinical Oncology Studies at the CVM
Disease
Study
Description
Inclusion/exclusion Incentive
PI
Brain tumors
(Glioma,
Meningioma)
1) Gene therapy +
immunotherapy vs.
immunotherapy alone
Study selected
based on diagnosis
MRI prior to
enrollment
No evidence of
systemic disease
Fully funded
Pluhar
A
Status
2) Gene therapy +
chemotherapy
3) Immunotherapy +
chemotherapy
Any histology,
*histiocytic
sarcoma
Compassionate use of
TTG100 in canine
spontaneous cancer
Safety and efficacy
of TTG100
ECG, PK series,
Visits Day 1, 22, 43,
71, 99
Any measurable
disease
SOC not successful
or declined
No anticancer therapy
for at least 3 weeks
prior to enrollment
Drug and PK levels
covered
$1,000 credit + $1,000
credit to owners of
Bernese Mountain
Dogs (from breed
club)
Henson
A
Various
histologies
*liver cancer
Microwave ablation +
immunotherapy
Safety and efficacy
of ultrasoundguided microwave
ablation combined
with adjuvant
Dogs and cats with
unresectable masses
amenable to
microwave ablation
Partially-funded
Ober
A
Any histology,
including breed
specific cohorts
COTC016: A Pilot Study
Assess feasibility
of tissue
collections and
molecular profiling
for future
comparative
oncology
personalized
medicine
Any measurable
disease
$1,000 credit to
owners + costs
associated with
sample collection
Henson
C
Clinical Oncology Studies at the CVM
Disease
Hemangiosarcoma
(HSA)
Study
Description
Dose-finding
Splenectomy and
doxorubicin
chemotherapy
PET-CT at baseline
and on day 21 if
abnormalities on
the initial scan
PK samples
2) MADGIC
Sample collection
1) OSAL (Salmonella-IL2)
PI
Status
Modiano
Borgatti
Vallera
A
Modiano
A
Splenic HSA
No evidence of
metastasis
Enrollment post
splenectomy
Study rechecks are
covered + $3,300
towards SOC
chemotherapy
All dogs with HSA
Samples/pathology
Safety and efficacy
Concurrent
doxorubicin
chemotherapy
Naïve appendicular
OS
$2,000 incentive
Wilke
A
2) miR31
Markers of
pulmonary
metastatic disease
Naïve appendicular
OS
Pays sample
collection
Kassie
Fritz
A
OS
Palladia/Piroxicam/Cyclop
hosphamide maintenance
therapy
Impact and efficacy
of maintenance
therapy following
amputation and
carboplatin
Microscopic, nonmetastatic OS
Partially-funded
Borgatti
C
Feline oral
squamous cell
carcinoma (SCC)
Protein kinase CK2
(nanocapsules)
Safety and efficacy
Oral SCC, regional
metastasis permitted,
no distant metastasis
or systemic disease
Treatment, rechecks,
up to $2,500 towards
adverse events
Cannon
A
Osteosarcoma
(OS)
1) SRCBST
Bispecific ligand targeted
toxin
Inclusion/exclusion Incentive
Clinical Investigation Center (CIC)
What Else Sets the UMN Apart?
A Few Select Examples:
• Translation of brain cancer therapy from dogs to humans
– “Successful Cancer Trial In Dogs Helping To Save Teenager”
• Prediction and prognosis for bone cancer patients
– “U of M researchers look to dogs to better understand
intricacies of bone cancer”
• Translation of cancer therapies from humans to dogs and
back
– Sal-IL-2 for bone cancer
– Minnelide™ for bone cancer
– “LICKing Lymphoma” – Novartis partnership targeting tumor
initiating cells
– Bispecific Ligand Targeted Toxin for hemangiosarcoma
– Gene therapy for liver tumors
What Have We Accomplished?
• Research success has allowed us to
establish a level of credibility in the
scientific community and created a
stable partnership between CVM and
MCC
• Success stories extend from the
laboratory to the clinic – advancing
translation