Panel on Access

1. Florida Society of Clinical Oncology: The Voice of Oncology in Florida
Emerging Immune-Oncology Therapies
Enhancing The Patient Experience Through Improving
Access Issues
Keith Knutson, PhD
Professor of Immunology, Mayo Clinic - Florida
Speaker
Lea Ann Biafora, MS, RN, OCN
Oncology Clinical Consultant, Humana
Moderator
Panelists
Katie Zacher, MBA
Director of Revenue, Florida Hospital
Don Champlain, RN, MHA
Associate Director for Care Management, Florida Cancer Specialists
Evania Nichols
Key Account Manager - Florida, Janssen Biotech

2. Florida Society of Clinical Oncology: The Voice of Oncology in Florida
http://www.asco.org/sites/new-www.asco.org/files/content-files/research-and-
progress/documents/2016-socca-infographic.pdf
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3. Bridge Between Patient and Provider
BarrierstoCancerCare
•Financial and
insurance concerns
(working, insurance
(co-pays, co-
insurance,
deductible),
prescription
coverage; housing
(utilities, food,
transportation)
•Clinical trial
opportunities
•Patient/Physician
Engagement and/or
Communication
•Support services
during treatment
•Psychosocial
concerns: cultural,
religious and person
values
ComplexDiseaseProcess
•Understanding
testing for
detecting cancer
•Understanding
the cancer
diagnosis and
extent of disease
•Need for care
coordination
•Diagnostic testing
and on-going
status checks
ComplexTreatment
•Informed decision
making with
treatment options
•Treatment
planning:
individualized drug
regimen choice
based on evidence-
pathways
•Treatment
oversight and care
coordination
•Symptoms, side
effects and quality
of life
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4. Florida Society of Clinical Oncology: The Voice of Oncology in Florida
• Review the evolution of immunotherapeutics.
• Review the mechanism of action and potential
side effects to immunotherapeutics used in cancer.
• Discuss key access barriers related to
immunotherapeutics.
• Discuss patient resources that address access
barriers in different settings.
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5. ©2014 MFMER | slide-5
Immune-based
Therapies: A Focus on
Access
Keith L. Knutson
Professor of Immunology
Director, Cancer Research, Mayo Clinic
Florida

6. ©2014 MFMER | slide-6
Conflict of Interest
• TapImmune, Inc.
• Cancer Vaccines – Jacksonville, FL
• Scientific Advisory Board (unpaid)
• Several Patent Licensing Agreements (Mayo)
• Kiromic, Inc.
• Cancer Vaccines – Lubbock, TX
• Scientific Advisory Board (Stock)
• Intelligent Immunity, Inc.
• Cancer Vaccines – Jacksonville, FL
• Scientific Advisory Board (Unpaid)
• Founder (Stockholder)
• Antigen Express, Inc.
• Cancer Vaccines – Cambridge, MA
• Scientific Advisory Board (Paid)

7. ©2014 MFMER | slide-7
textbookofbacteriology.com
Cells of the Immune System

8. ©2014 MFMER | slide-8
CD4 “helper” T cells
•Inflammation (macrophages and
neutrophils)
•Antibodies
•Induce/Enhance cytotoxic T cells
•Immune-surveillance
•Epitope-spreading
•Cytokines
CD8 “cytolytic” T cells
•Tumor lysis
B cells
•Antibodies
•Signaling
•ADCC
•Complement
The adaptive immune response

9. ©2014 MFMER | slide-9
1890 1956 1973 1997 2000 2002-3 2010 2012
Coley’s Toxins
tried in humans
Today
Identification of tumor
antigens
The first
monoclonal
antibody,
Rituximab is
approved to treat
B cell lymphoma
Adoptive cell
therapy with TILs
is first described
Immunotherapy for cancer: 100 years of
science
Dendritic cells
are discovered
1978
• BCG is first studied as a
therapy
• IL-2 is discovered
• Tumor-specific antibodies
are discovered
1988
BCG
approved for
bladder
cancer
1990 1998
• IL-2 approved to treat
metastatic melanoma
• Trastuzumab is approved
for breast cancer
Gemtuzumab
ozogamicin, an
antibody toxin
conjugate is
approved for AML
Two
antibody/radioisotope
conjugates,
Ibritumomab tiuxetan
and Iodine I 131
Tositumab are
approved
First therapeutic cancer
vaccine, sipuleucel, is
approved by the FDA
2011
Ipilimumab is
approved for
melanoma
Several clinical
studies
demonstrate the
therapeutic activity
of PD-1/PD-L1
blockade
2014
Nivolumab and
Pembrolizumab are
approved for
advanced
melanoma

10. ©2014 MFMER | slide-10
Clinical Trial Sponsorship
• Physicians
• Scientists
• Medical Institutions
• Foundations
• Voluntary Groups
• Pharmaceutical Companies
• Federal Agencies (cooperative group research)
• NIH
• NCI (ACRIN is funded through the NCI as a cooperative group)
• DOD
• VA

11. ©2014 MFMER | slide-11
Phase 0
• Recent designation for exploratory,
first-in-human trials
• Expedite the development of
promising therapeutic or imaging
agents
• Involve the administration of single
sub therapeutic doses to a small
number of subjects (10-15).
• Preliminary data on the
pharmacokinetic and
pharmacodynamic properties and
mechanism of action.
Phase I
• Typically first step in testing in
humans.
• Researchers look for safety and
potentially harmful side effects.
• Usually include only a limited
number of human subjects (20-
80).
• This phase of testing usually takes
several months.
• Multiple different kinds of Phase I
trials.
• Preliminary data on efficacy and
pharmacology.

12. ©2014 MFMER | slide-12
Phase II
• Once a drug has shown to
be safe, then it must be
tested for efficacy.
• This phase may last from
several months to a few
years.
• Usually involves several
hundred patients
• Most of these trials are
randomized trials
Phase III
• Randomized control trials
(300-3000).
• Compare the results of the
patients on the experimental
trial to those patients
utilizing standard diagnostic
studies, standard treatment,
or placebo.
• Multi-center trials.
• Many phase III trials are
randomized and blinded.

13. ©2014 MFMER | slide-13
BC141410: FRa Vaccination to Prevent
Progression of Triple Negative Breast
Cancer
Stages IIb/III
TNBC
Placebo
N=93
Vaccine
N=187
Conventional
Therapy
• Multicenter Phase II Trial to Test Whether Vaccine
Prevents Recurrence in Patients Diagnosed and
Treated for TNBC
FRa is preferentially overexpressed in TNBC

14. ©2014 MFMER | slide-14
Complex Eligibility
Specification
Limits Access to
Most Advanced
Clinical Trials:
Example of Phase
II of Vaccine Trials
• No evidence of disease.
• Within one year of standard
of care treatment.
• Recurrent cancer ineligible.
• Existing or preexisting
autoimmune disease.
• Target expression
Side Effects of Cancer
Vaccination
• Fatigue
• Injection site
reactions
• Nausea

15. ©2014 MFMER | slide-15
aBased on small subgroups of patients with HER2-positive breast cancer;
bDDFS; CTx, chemotherapy; AC, doxorubicin, cyclophosphamide;
P, paclitaxel; T, docetaxel; Carbo, carboplatin; V, vinorelbine;
CEF, cyclophosphamide, epirubicin, 5-fluorouracil
DFS benefit for Trastuzumab in Adjuvant Trials
3
4
5
4
Gianni et al 2008;
Gianni et al 2009; Joensuu et al 2009;
Slamon et al 2006; Perez et al 2007;
Smith et al 2007; Spielmann et al 2007;
Perez 2005
3
3
Median follow-up, years/HRDFS benefit
B-31 / N9831 ACPH
HERA CTxH 1 year
FinHera VH / THCEFb
PACS-04a CTxH 1 year
BCIRG 006 ACTH
TCarbo H
n=231
n=528
NOAH CTx / HH 1 year 3
0 1 2Favors
Trastuzumab
Favors no
TrastuzumabHR
Chemotherapy plus Trastuzumab administered for 1 yr represents the standard of care
On average, this treatment induces a 50% reduction in HR for relapse in all subgroups of pts,
especially concurrent with chemo
N9831 ACP  H 1.5 0.87
0.48
0.64
0.61
0.67
0.86

16. ©2014 MFMER | slide-16
Proposed mechanisms of action of
trastuzumab

17. ©2014 MFMER | slide-17
Trastuzumab – Side Effects
• Fever
• Nausea
• Vomiting
• Diarrhea
• Infections
• Increased cough
• Headache
• Fatigue
• Shortness of breath
• Rash
• Low white and red cells
• Muscle pain
MOST COMMON SEVERE
• Reduced heart function
• Congestive heart failure
• Swelling of the lungs
• Severe shortness of
breath
• Fetal death

18. ©2014 MFMER | slide-18
Discovery Medicine
Adoptive T cell therapy with CAR T cells
LIMITATIONS
• Production of a recombinant transgenic construct to modify T cells
from patient.
• High cost expansion infrastructure to grow T cells

19. ©2014 MFMER | slide-19
Side effects associated with CAR T cell therapy
Mol Therapy 2016
LIMITATION
• Tumor must have
specific target
expressed

20. ©2014 MFMER | slide-20
The Checkpoint Blockade Revolution
Lymphomation.org

21. ©2014 MFMER | slide-21
Side Effects of Immune Checkpoint Inhibitors
Cancergrace.org

22. ©2014 MFMER | slide-22
Other Factors that Limit Access of Patients to
Clinical Trials
• Insurance: No formal agreements or industry policy on
what components of a clinical trial are covered by
insurance companies. Limits activating trials.
• Awareness: Community physicians are unaware of trials.
• Resources: Community physicians and clinics lack
resources to become involved in clinical trials.
• Adverse event risk: Trials are not attractive to potential
participants.
• Industry interests: Early testing is regulated by company
because of strategic interests and limited resources.

23. ©2014 MFMER | slide-23
• Increase
research
transparency
• Help people
find trials
ClinicalTrials.gov can be searched
in real time to find enrolling and
completed studies including:
• Conditions
• Interventions
• Outcome measures
• Sponsors/collaborators
• Locations
• Phases
• Dates (Start and Completion)
• Results

24. ©2014 MFMER | slide-24
http://www.ClinicalTrials.gov

25. ©2014 MFMER | slide-25

26. Florida Society of Clinical Oncology: The Voice of Oncology in Florida
Access
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27. Florida Society of Clinical Oncology: The Voice of Oncology in Florida
• Financial and insurance concerns (working, insurance: co-pays, co-insurance,
deductible), prescription coverage; housing (utilities, food, transportation)
• Clinical trial opportunities
• Patient/Physician Engagement and/or Communication
• Support services during treatment
• Psychosocial concerns: cultural, religious and person values
Access Barriers Related to Immunotherapeutics in Cancer Care
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28. Florida Society of Clinical Oncology: The Voice of Oncology in Florida
Do You Know Your Coverage ?
1. Coverage for treatment regimens are based upon what guidelines?
A. FDA
B. NCCN
C. Payor developed guidelines
D. Combination of all or some of the above
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29. Florida Society of Clinical Oncology: The Voice of Oncology in Florida
Do You Know Your Coverage ?
2. Drug Replacement Programs are available for certain drugs if a patient is
A. Uninsured
B. Underinsured
C. Insured
D. All of the Above
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30. Florida Society of Clinical Oncology: The Voice of Oncology in Florida
Do You Know Your Coverage ?
3. Financial Assistance through a variety of Foundation/Programs are
available to:
A. Uninsured
B. Insured
C. Underinsured
D. All of the Above
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31. Florida Society of Clinical Oncology: The Voice of Oncology in Florida
Do You Know Your Coverage ?
4. If you are not uninsured or underinsured, you are not able to obtain
financial assistance.
A. True
B. False
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32. Florida Society of Clinical Oncology: The Voice of Oncology in Florida
Financial Toxicity of Cancer
• 32% of cancer patients report cancer-related financial problems.
• 23% of cancer patients reporting that they postponed
recommended health care due to cost.
• Cancer patients are 2.65x more likely to go bankrupt than people
without cancer.
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33. Florida Society of Clinical Oncology: The Voice of Oncology in Florida
Financial Toxicity of Cancer
Population Median Annual
Household
Income
Average Annual
Cost of Cancer
Cost of Cancer as
Percentage of Average
Household Income
Under 65 years $57,353 $16,213 28%
65 and older $33,848 $16,441 49%
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34. Florida Society of Clinical Oncology: The Voice of Oncology in Florida
Patient Propensity to Pay, by Deductible Size
10%
20%
30%
40%
50%
60%
70%
80%
$500 - $999 $1,000 - $2,000 $2,001 - $3,500 $3,501 - $5,000 $5,001 - $6,350
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35. Florida Society of Clinical Oncology: The Voice of Oncology in Florida
Challenges within Immunotherapy
• What are some ways nurse navigators can keep abreast of new classes and expanded indications of
immunotherapeutic agents?
• How best to address the right drug/person when patients ask about candidacy for immunotherapy for
treatment and/or clinical trial?
• How do we coordinate care as patient life expectancies increase as a result of immunotherapy?
Access Barriers Related to Immunotherapeutics in Cancer Care
• Would you share best practices on how your institution addresses:
– Financial and insurance concerns (working, insurance prescription coverage; housing (utilities, food, transportation)
– Clinical trial opportunities
– Patient/Physician Engagement and/or Communication
– Support services during treatment
– Psychosocial concerns: cultural, religious and person values
Roundtable Discussion on:
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36. Florida Society of Clinical Oncology: The Voice of Oncology in Florida
Discuss patient resources that address access barriers in different settings.
• Cancer Care: 2016 Patient Access and Engagement Report
https://media.cancercare.org/accessengagementreport/Highlights-SlidesMay2016pdf.pdf
• Cancer Research Institute: TheAnswerToCancer.org
http://www.theanswertocancer.org/
• Society for Immunotherapy of Cancer: Free patient resource on Understanding Cancer
Immunotherapy and Immunotherapy for the treatment of Melanoma. www.sitcancer.org
• The Advocacy Connector www.advocacyconnector.com
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