Colorado Cancer Coalition
Quarterly Coalition Meeting Date: October 27, 2016 Time: 2:00pm - 4:00pm Facilitator: Dr. Madeleine Kane
American Cancer Society Office - Brooks Conference Center, 2255 S. Oneida St., Denver, CO
Location
Remote information: Livestream Link: https://echo.zoom.us/j/7648943828 A phone number will be provided after logging in to the meeting RSVP Here: https://www.eventbrite.com/e/colorado-cancer-coalitionquarterly-meeting-tickets-28188854623 Meeting Purpose
Time
Colorado Cancer Coalition and Task Force Updates
Topic
2:00 pm 2:10 pm
Introductions
2:10- 2:40
Coalition Updates
Lead
Dr. Madeleine Kane
Notes
● ●
●
Journey Connections Update New Committees to Join ○ Checkoff Communications ○ Resource/Fundraising ○ Resource Directory ○ Patient Advisory Committee ○ Symposium ○ Clinical Trials/Treatment Task Force ○ Interested in joining a committee? CCC Financials
Page 1 of 8
2:40- 3:00
Task Force Updates
Task Force Chairs
3 Task Forces will provide updates. Other Task Force written updates are included in the agenda ● Lung Cancer- PPT Slides ● Survivorship - PPT Slides ● Family History
3:00 - 3:30
Immunotherapy Presentation
Dr. Karl Lewis
PPT Slides
3:30-3:40
Environmental Scans
Eric Taber
3:40 - 3:50
New Business
Dr. Madeleine Kane
3:50 pm
Partner Updates 2017 Quarterly Meeting Dates
Add your own calendar event to the CCC calendar- How To File Share programs and events from your organization January 26, 2017 2-4 pm ACS – Brooks Conference Center Zoom will be available April 2017 TBD- Will likely be a 1-1.5 day symposium instead of Quarterly Meeting July 27, 2017 12-2 pm Location TBD Zoom will be available October 26, 2017 2-4 pm Location TBD Zoom will be available
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TASK FORCE UPDATES **Meeting info may change. If you are not on the Task Force distribution list, be sure to contact the chair to confirm the meeting information** BREAST CANCER TASK FORCE Task Force
Chairs
Contact Info
Meeting Date
Breast Cancer Task Force
Brandy Brogan
bbrogan@projectangelh eart.org
November 17th 9:30-11am. American Cancer Society, 2255 S Oneida St, Denver, CO
Breast Cancer Task Force Update Next meeting is from 9:30-10am on November 17th. There will be an opportunity to network and connect with other members of the task force at the beginning of the meeting. The Breast Cancer Task Force published an advertisement in the Colorado Nurses magazine that goes out to 72K ppl. They are hoping to bring awareness to everyone that IBC is also a concern and one that is less known. As knowledge is power they will be creating some slides about self-breast exams, screening info, connection information, and how to talk about breast cancer so individuals can include those in presentations they are already doing. COLORECTAL CANCER TASK FORCE Task Force
Chairs
Contact Info
Meeting Date
Colorectal Cancer Task Force
Jane Harris and Jackie Woods
[email protected] [email protected] rg
November 10th, 7:30 am - 8:30 am December 8th, 7:30 am - 8:30 am January 12, 2017 7:30 am - 8:30 am LOCATION: American Cancer Society, 2255 S Oneida St, Denver, CO
Colorectal Cancer Task Force Update No update was submitted. FAMILY HISTORY TASK FORCE Task Force
Chairs
Contact Info
Meeting Date
Family History Task Force
Emily Fields facilitating for now
[email protected] s
Nov 21st, 8:00 - 9:30 am Dec19th, 8:00 - 9:30 am Jan 16, 2017, 8:00 - 9:30 am All via Zoom: https://zoom.us/j/9781446096 Page 3 of 8
Family History Task Force Update We’re working on providing a list of resources on the CCC website. Do you have a particular family history risk assessment tool that you recommend we include? If so please email it to
[email protected] Do you know a genetic counselor who should be on this Task Force? Please send their information to
[email protected] FINANCIAL BARRIERS TASK FORCE Task Force
Chairs
Contact Info
Meeting Date
Financial Barriers Task Force
Toni Panetta and Tim Taravella
TPanetta@komencolora do.org ttaravella@senseofsecu rity.org
Oct 21, 12:00 - 1:30 pm Nov 18, 12:00 - 1:30 pm Dec 16, 12:00 - 1:30 pm Jan 20, 2017, 12:00 - 1:30 Location: Colorado Foundation for Public Health and the Environment 1385 S. Colorado Blvd. Suite 622 Denver, CO 80222 Zoom remote link for all meetings: https://zoom.us/j/9781446096
Financial Barriers Task Force Update The Financial Barriers Task Force held its second meeting on October 21. The group is working on updating the Action Plan, completing the Environmental Scan and the Resource Directory. At the first meeting in August, participants were asked to review two documents shared by Toni Panetta - Patient Self-Advocacy Reference: https://drive.google.com/file/d/0BzprTC59c3WnR2M2cVh1M0FjNU9qUExYVjJGckdmSi02Z3lv/view?u sp=sharing Checklist for Insurance Purchasing: https://drive.google.com/file/d/0BzprTC59c3WnTHNVQTdqeDhGbWROVHhSYmFELThrX2FYMVBr/vie w?usp=sharing The Task Force is looking for a co-chair. Our next meeting is November 18. HPV PREVENTION TASK FORCE Task Force
Chairs
Contact Info
Meeting Date
HPV Prevention Task Force
Eric Taber
[email protected]
Nov 16, 10 am - 11:00 am - CDPHE Building C, Room C1E https://zoom.us/j/539214139 Dec 8, 10 am - 11:00 am - CDPHE Building C, Room C1E https://zoom.us/j/765832629 Jan 12, 2017, 10 am - 11:00 am - CDPHE Building A, Snow Room Page 4 of 8
https://zoom.us/j/638712777 HPV Task Force Update At this month’s task force meeting, we finalized our ‘pitch’ of what the task force can offer and we’re reaching out to LPHAs and school nurses to offer our assistance and grow our membership base. We also initiated discussions with Denver Public Schools about their health education curriculum. Furthermore, we reviewed existing HPV educational materials (i.e. infographics and fact sheets) and we plan to coordinate with the Denver Metro Alliance for HPV Prevention to push out pieces of their communications campaign to a larger, statewide audience. Finally, we’ve identified community events where we can raise awareness about HPV vaccination, and this week we were at the Crucial Catch Day hosted by ACS and MCPN. LUNG CANCER TASK FORCE Task Force
Chairs
Contact Info
Lung Cancer Task Force
Dr. Debby Dyer and Dr. Jim Fenton
[email protected] [email protected]
Meeting Date Dec 13, 5:30 pm Location: National Jewish Health, Room L111, 1400 Jackson Street, Denver CO 80206 Conference Call: 1-888-875-1833 Passcode: 93561200
Lung Cancer Task Force Update Update will be provided at the meeting. OVARIAN CANCER TASK FORCE Task Force
Chairs
Ovarian Cancer Task Force
Mary Phillips
Contact Info
Meeting Date
Ovarian Cancer Task Force Update No update was submitted. PATIENT NAVIGATION TASK FORCE Task Force
Chairs
Patient Navigation Task Force
Morgan Nestingen and Ron Brady
Contact Info
Meeting Date October 26, 2-3 pm American Cancer Society, 2255 S Oneida St, Denver, CO Zoom remote link for all meetings: https://zoom.us/j/9781446096 Page 5 of 8
Patient Navigation Task Force Update No update was submitted. SKIN CANCER TASK FORCE Task Force
Chairs
Skin Cancer Task Force
Jessica Mounessa and Dr. Robert Dellavalle
Contact Info
Meeting Date Nov 8, 2 - 3 pm Dec 13, 2-3 pm Denver VA, Neurology Conference Room, 1055 Clermont St. Room 6a-121, Denver CO 80220 Conference Call
Skin Cancer Task Force Update ●
● ●
●
●
Our work was recently featured in the Denver Post ( http://www.denverpost.com/2016/10/10/colorado-sunscreen-melanoma/) and in the CDC Success Story, "Specialized Photography Promotes Sun Safety in Colorado” (attached). Klein Buendel has received a mini-grant from the CDPHE to disseminate sun safety curriculum in 200 high altitude CO schools. Drs. Lori Crane and Nancy Asdigian from the Colorado School of Public Health and Dr. Dellavalle from the Department of Dermatology have begun a 2-year project funded by the CCPD to promote skin cancer prevention on 10 college campuses across Colorado. We have participated in a number of outreach events including the Summit Melanoma, Bronco’s Wellness Fair, UPS Health Fair, Colorado Cancer and Wellness Conference. At these events we have provided sunscreen and educated participants on skin cancer prevention using our specialized cross-polarized light photography revealing sun damage. We will be involved in the upcoming Cancer Screening Provider Training. SURVIVORSHIP TASK FORCE
Task Force
Chairs
Contact Info
Meeting Date
Survivorship Task Force
Cathy Bledsoe and Sandy Priester
[email protected] m
Physical Health Work Group Nov 2, 9 am Dec 7, 9 am Jan 4, 2017 9 am Location: Project Angel Heart 4950 Washington St., Denver, CO 80216 Remote connection: https://zoom.us/j/9781446096
[email protected] g (Mental and Physical Health Workgroup contact)
Mental Health Work Group Nov 14, 1:00 pm Dec 12, 1:00 pm Jan 9, 2017, 1:00 pm Location: Colorado Department of Public
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Health and Environment (CDPHE) 4300 Cherry Creek Drive South, Denver, CO 80246 Remote connection: https://zoom.us/j/9781446096
Transition Work Group - TBD Legislative/Reimbursement Work Group TBD Survivorship Task Force Meeting - TBD Survivorship Task Force Update Update will be provided at the meeting. SCREENING COORDINATING COMMITTEE Task Force
Chairs
Contact Info
Meeting Date
Screening Coordinating Committee
Ian Kahn and Becky Selig
[email protected] [email protected] s
Oct 18, 2-3 pm Nov 15, 2-3 pm Dec 20, 2-3 pm Jan 17, 2017, 2-3 pm Location: American Cancer Society 2255 S Oneida St, Denver, CO Conference: Call in: 323-484-8105 Conference ID: 7534474
Screening Coordinating Committee Update We are working to finalize the mission of this committee - key points that we'd like to include are: ● ● ● ● ●
Core space to coordinate disparate rates of screening Synergize work that each task force is doing, avoiding overlap/duplication Identify areas of collaboration Share what all are currently doing on own (and across task forces), identify ways others can support and work on new projects together Collaborate on ways we can have a greater impact on policies and other systems level work that relates to screening
Projects/collaborations being discussed include: ● ●
Early stages of looking into the feasibility of a state-wide screening registry Very early stages of discussing a public-facing screening website/assessment tool ○ Potentially start with a health assessment of sorts, would provide users with information on which screenings they are due for) ○ Expand to other functionalities like connecting to resources and specific patient needs
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●
Potential 9HealthFair collaboration
Upcoming Provider Training for the primary care workforce - Nov. 4 - please share with your networks ●
Cancer Screening session from 12:30-4:30pm. More information and to register here: http://tinyurl.com/NovProviderTraining
Action Needed: For remote attendees - Please fill in this survey at the conclusion of the meeting: https://www.surveymonkey.com/r/CCCquarterlyfeedback
Websites: Colorado Cancer Coalition: http://www.coloradocancercoalition.org/ Colorado Cancer Plan: https://www.colorado.gov/cancerplan
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Colorado Cancer Coalition Standing Committees ○
Resource Committee - Lead: Dr. Cathy Bradley ■ Develop resource plan and sponsorship packets to fund CCC activities. ■ Research grants and companies for potential funding opportunities. ■ On-going committee
○
Annual Symposium Committee - Lead: Dr. Tim Byers ■ Plan and execute the Annual Symposium. ■ Acquire speakers for the Symposium. ■ Acquire sponsors for the Symposium. ■ Primary time commitment: November - April
○
Colorado Cancer Fund: ■ Colorado Cancer Fund Communications - Lead: Cindi Vogt ● Develop communications plan to spread awareness of the check off fund. ● Acquire sponsors to cover advertising expenses. ● Primary time commitment: November - April ■ Colorado Cancer Fund Grantors: ● Review Cancer Fund applications and award competitive grants. ● Primary time commitment: Aug - Nov
○
Resource Directory Committee: ■ Review resources (as necessary). ■ Plan the development of the online resource directory. ■ Discuss the possibility of a printed directory. ■ On-going committee
○
Patient Advisory Committee: ■ A group of patients and survivors that are available to provide feedback as needs arise. ■ On-going. Ad hoc emails and meetings as necessary
○
Communications Committee: ■ Develop communications plan to broadcast Coalition messaging across the state. ■ On-going committee
If anyone is interested in joining a committee, please contact c
[email protected] and
[email protected]
Colorado Foundation for Public Health and the Environment Statement of Activities From 1/1/2016 Through 12/31/2016
CCC - Colorado Cancer Coalition (In Whole Numbers) Total Operating Revenue Contributions Contributions - Business Contributions - Nonprofit/Foun Total Contributions
3,000 16,935 19,935
Total Operating Revenue
19,935
Total Operating Revenue
19,935
Total Revenue
19,935
Operating Expenses Professional Fees Contractor Fees
3,055
Total Professional Fees
3,055
Non-Personnel Expenses Supplies Total Non-Personnel Expenses
158 158
Conferences, Conventions & Meetings Conference/Meeting Food Total Conferences, Conventions & Meetings
52 52
Miscellaneous Web Hosted Business Tools Total Miscellaneous Total Operating Expenses
341 341 3,607
Inter-Company Expenses Foundation Fiscal Service Fees Total Inter-Company Expenses
1,615 1,615
Total Expenses
(5,221)
Net Revenue Over Expenditures
14,714
Ending Fund Balance
14,714
Date: 10/26/2016, 11:12 AM
Page: 1
10/25/2016
Immunotherapies Karl Lewis, MD Associate Professor University of Colorado Aurora, CO
Treatment Options for Cancer • Surgery • Radiation • Systemic therapies: – Chemotherapy – Hormonal therapy – Immune therapy – Targeted therapy
Treatment Options for Cancer • Surgery • Radiation
Local therapies
• Systemic therapies: – Chemotherapy – Hormonal therapy – Immune therapy – Targeted therapy
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Systemic Therapies • Chemotherapy: chemicals given to poison growing and dividing cells (cytotoxic)
Chabner BA, Roberts TG. Nat Rev Cancer. 2005;5:65-72.
Systemic Therapies (cont.) • Hormonal therapy: some cancers (breast, prostate) are sensitive to hormones – Blocking or changing hormone balance can lead to cancer cell death.
Tamoxifen
Leuprolide
Systemic Therapies (cont.) • Targeted therapies: – Proof of concept: CML results from very specific chromosomal translocation. – 2001: approval of imatinib based on work from Brian Druker at OHSU "There is no question that we can defeat cancer. What it requires is knowledge. When we understand what is broken, we can fix it." ‐ Brian Druker, M.D., Director, OHSU Knight Cancer Institute CML = chronic myelogenous leukemia
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Systemic Therapies (cont.) • Immunotherapy: a treatment that uses the body’s own immune system to help fight cancer.
Immunology Terms • Antigen: substance that induces an immune response in the body • Antibody: a circulating protein that binds to a specific antigen • Lymph node: small structures that contain immune cells and filter lymphatic fluid • Cytokines: secreted substances of immune cells that have an effect on other cells (interferon, interleukin, etc.)
Major Players in Cancer Immunology • CD8+ cytotoxic T cells (Tc): cells that kill cancer cells, cells that are infected (e.g., with viruses), or cells that are damaged in other ways. • CD4+ helper T cells (Th): help the activity of other immune cells by releasing cytokines (e.g., stimulate B cell antibody secretion). • Dendritic cells = antigen presenting cells (APC): process antigen and present it on the cell surface to T cells. • Regulatory T cells (Treg): immunosuppressive
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Cancer Immunity Cycle 4 3
Priming & activation (APCs and T cells)
T-cell trafficking to tumours (CTLs) 5
2
T-cell infiltration into tumours (CTLs, endothelial cells)
blood vessel
Antigen presentation (DCs and other APCs)
lymph node 6
T-cell recognition of cancer cells
7
Killing of cancer cells
tumour 1
Antigen release (cancer cell death)
Chen DS, Mellman I. Immunity. 2013;39:1–10.
Immunotherapy Milestones Immunotherapy Milestones
Melero I, et al. Nat Rev Clin Oncol. 2014;11:509–524.
William B. Coley • 1890’s: Injected first pt with streptococcal organisms based on reports of cancer regression in pts developing infections • Coley’s Toxin: heat-killed Streptococcus and Serratia sp. • Injected over 1,000 pts throughout his career • Significant criticism based on inconsistent and nonreproducible results.
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Regression of Primary Melanoma
Vitiligo of Metastatic Melanoma
High-dose IL-2 in Metastatic Melanoma
Survival for the whole study population (270 patients) treated with high-dose IL2
Probability of Survival
1.0
Survival for the whole study population (270 patients) treatedMedian with high-dose IL-2 survival 11.4 months
0.8
0.6 0.4 0.2
0.0 0
12
24
36
48
72 60 Months
84
96
108
120
132
Atkins MB, et al. J Clin Oncol. 1999;17:2105.
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PET Scans of Melanoma Patient Treated with IL-2
Immune Cytokines: IL-2 • Proof that immune system can control/eliminate cancer • Unable to select patients who will respond • Associated with high toxicity
Monoclonal Antibodies as Cancer Therapy • Antibodies that are designed to specifically target certain antigens, particularly antigens that are found on cancer cells • Generally not naturally occurring antibodies • Chimeric antibodies: consist of both mouse and human elements Image retrieved from: http://www.cancerresearchuk.org/file/53146
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Tumor-associated Antigens Targeted by Therapeutic Monoclonal Antibodies Antigen category
Examples of antigens
Examples of therapeutic mAbs raised against these targets
Tumour types expressing antigen
Haematopoietic differentiation antigens
CD20
Rituximab
Non-Hodgkin’s lymphoma
Ibritumomab tiuxetan and tositumomab
Lymphoma
CD30
Brentuximab vedotin
Hodgkin’s lymphoma
DC33
Gemtuzumab ozogamicin
Acute myelogenous leukemia
CD52
Alemtuzumab
Chronic lymphocytic leukemia
EpCAM
IGN101 and adecatumumab
Epithelial tumors (breast, colon and lung)
Labetuzumab
Breast, colon and lung tumors
Glycoproteins expressed by solid tumors
CEA gpA33
huA33
Mucins
Pemtumomab and oregovomab
Breast, colon, lung and ovarian tumors
TAG-72
CC49 (minretumomab)
Breast, colon and lung tumors
Colorectal carcinoma
CAIX
cG250
Renal cell carcinoma
PSMA
J591
Prostate carcinoma
Folate-binding protein
MOv18 and MORAb-003 (farletuzumab)
Ovarian tumors
Glycolipids
Gangliosides (such as GD2, GD3 and GM2)
3F8, ch14.18 and KW-2871
Neuroectodermal tumors and some epithelial tumors
Carbohydrates
Le
hu3S193 and IgN311
Breast, colon, lung and prostate tumors
Scott AM, Wolchok JD, Old LJ, et al. Nat Rev Cancer. 2012;12:278-287.
Tumor-associated Antigens Targeted by Therapeutic Monoclonal Antibodies Examples of therapeutic mAbs raised against these targets
Tumour types expressing antigen
VEGF
Bevacizumab
Tumor vasculature
VEGFR
IM-2C6 and CDP791
Epithelium-derived solid tumors
Integrin αVß3
Etaracizumab
Tumor vasculature
Integrin α5ß1
Volociximab
Tumor vasculature
EGFR
Cetuximab, panitumumab, nimotuzumab and 806
Glioma, lung, breast, colon, and head and neck tumors
ERBB2
Trastuzumab and pertuzumab
Antigen category
Examples of antigens
Targets of antiangiogenic mAbs
Growth and differentiation signaling
MM-121
Breast, colon, lung, ovarian and prostate tumors
MET
AMG 102, METMAB and SCH 900105
Breast, ovary, and lung tumors
IGF1R
AVE1642, IMC-A12, MK-0646, R1507 and CP 751871
Glioma, lung, breast, head and neck, prostate and thyroid cancer
EPHA3
KB004 and IIIA4
Lung, kidney and colon tumors, melanoma, glioma and hematological malignancies
TRAILR1
Stromal and extracellular matrix antigens
Breast, colon, lung, ovarian and prostate tumors
ERBB3
Mapatumumab (HGS-ETR1)
TRAILR2
HGS-ETR2 and CS-1008
RANKL
Denosumab
Colon, lung and pancreas tumors and hematological malignancies Prostate cancer and bone metastases
FAP
3F8, ch14.18 and KW-2871
Neuroectodermal tumors and some epithelial tumors
Tenascin
81C6
Glioma, breast and prostate tumors
Scott AM, Wolchok JD, Old LJ, et al. Nat Rev Cancer. 2012;12:278-287.
FDA-approved Monoclonal Antibodies and Their Mechanisms of Action Antibody
Target
FDA-approved indication
Mechanisms of action
Naked antibodies: solid malignancies Trastuzumab: humanized IgG1
ERBB2
ERBB2-positive breast cancer, as a single agent or in combination with chemotherapy for adjuvant or palliative treatment
Inhibition of ERBB2 signaling and ADCC
ERBB2-positive gastric or gastro-esophageal junction carcinoma as first-line treatment in combination with cisplatin and capecitabine or 5-fluorouracil Bevacizumab: humanized IgG1
VEGF
For first-line and second-line treatment of metastatic colon cancer, in conjunction with 5-fluorouracil-based chemotherapy; for first-line treatment of advanced NSCLC, in combination with carboplatin and paclitaxel, in patients who have not yet received chemotherapy; as a single agent in adult patients with glioblastoma whose tumor has progressed after initial treatment; and in conjunction with IFNα to treat metastatic kidney cancer
Inhibition of VEGF signaling
Cetuximab: chimeric human-murine IgG1
EGFR
In combination with radiation therapy for the initial treatment of locally or regionally advanced SCCHN; as a single agent for patients with SCCHN for whom prior platinum-based therapy has failed; and palliative treatment of pretreated metastatic EGFR-positive colorectal cancer
Inhibition of EGFR signaling and ADCC
Panitumumab: human IgG2
EGFR
As a single agent for the treatment of pretreated EGFRexpressing, metastatic colorectal carcinoma
Inhibition of EGFR signaling
Ipilimumab: IgG1
CTLA4
For the treatment of unresectable or metastatic melanoma
Inhibition of CTLA4 signaling
Scott AM, Wolchok JD, Old LJ, et al. Nat Rev Cancer. 2012;12:278-287.
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FDA-approved Monoclonal Antibodies and Their Mechanisms of Action Antibody
Target
FDA-approved indication
Mechanisms of action
Naked antibodies: hematological malignancies Rituximab: chimeric human-murine IgG1
CD20
For the treatment of CD20-positive B cell NHL and CLL, and for maintenance therapy for untreated follicular CD20positive NHL
ADCC, direct induction of apoptosis and CDC
Alemtuzumab: humanized IgG1
CD52
As a single agent for the treatment of B cell chronic lymphocytic leukemia
Direct induction of apoptosis and CDC
Ofatumumab: human IgG1
CD20
Treatment of patients with CLL refractory to fludarabine and alemtuzumab
ADCC and CDC
Conjugated antibodies: hematological malignancies CD33
For the treatment of patients with CD33-positive acute myeloid leukemia in first relapse who are 60 years of age or older and who are not considered candidates for other cytotoxic chemotherapy; withdrawn from use in June 2010
Brentuximab vedotin: chimeric IgG1
CD30
Fr the treatment of relapsed or refractory Hodgkin’s lymphoma and systemic anaplastic lymphoma
Delivery of toxic payload, auristatin toxin
90Y-labeled
CD20
Treatment of relapsed or refractory, low-grade or follicular B cell NHL
Delivery of the radioisotope 90Y
CD20
Treatment of patients with CD20 antigen-expressing relapsed or refractory, low-grade, follicular or transformed NHL
Gemtuzumab ozogamicin: humanized IgG4
ibitumomab tiuxetan: murine IgG1
Delivery of toxic payload, calicheamicin toxin
Previously untreated follicular NHL in patients who achieve a partial or complete response to first-line chemotherapy
131I-labeled
tositumomab: murine IgG2
Delivery of the radioisotope ADCC and direct induction of apoptosis
131I,
Scott AM, Wolchok JD, Old LJ, et al. Nat Rev Cancer. 2012;12:278-287.
Rituximab Fc
Heavy-chain (gamma) constant region
Fab
Light-chain (kappa) constant region Light-chain (anti-CD20) variable region Heavy-chain (anti-CD20) variable region
Figure above Rituximab is a chimeric antibody of the immunoglobulin G1 kappa type with murine anti-CD20 variable-sequence regions (filled areas) and human constant-sequence regions (open areas).
Wood AM. Am J Health Syst Pharm. 2001;58(3).
Rituximab Added to Standard Chemotherapy Addition of rituximab to standard chemotherapy improved the overall and event-free survival of patients with lymphoma
Fu K, et al. JCO. 2008;26:4587-4594.
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Vaccines • A preparation that is administered to produce or artificially increase immunity to a particular disease • Have been tested for several decades, but advances in this field have been slower than for other forms of immunotherapy • Therapeutic and preventative
Preventative Vaccines • Some cancers are caused by viruses. Vaccines that protect against infections with these viruses may prevent cancer. • HPV: cervical, anal, throat • HBV: liver cancer
Therapeutic Vaccines • Instead of preventing disease, they are meant to get the immune system to attack a disease that already exists • Made up of cancer cells, parts of cells, or pure antigens that try to get the immune system to attack cells with those specific antigens • Many have been or are under investigation • Overall, very disappointing results • Only one therapy approved by the FDA to treat advanced cancer to date
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Sipuleucel-T for Advanced Prostate Cancer Figure: The diagram illustrates the two steps involved in sipuleucel-T therapy: (1) harvesting the patient’s dendritic cells and then pulsing these ex vivo with a recombinant fusion protein made of prostatic acid phosphatase (PAP) and granulocytemacrophage colonstimulating factor (GMCSF); and (2) infusing the cultured cells into the patient, where the PAP-GM-CSF-loaded antigen-presenting cells induce the proliferation of T-cells that recognize and target prostate tumor cells.
Garcia JA, Dreicer R. 2011. Diagn Imaging. 2011;1-11.
D9902B – IMPACT R A N D O M I Z E
mCRPC No Visceral Mets N = 512
Placebo q2wks x3
Sipuleucel-T q2wks x 3
Patients: Asymptomatic or minimally symptomatic mCRPC Primary end point: OS Secondary end point: TTP
P R O G R E S S I O N
Eligible for Sipuleucel-Ta
Physician’s Discretion
aPrepared
from cryo-preserved lymphocytes. IMPACT = immunotherapy prostate adenocarcinoma treatment; mCRPC = metastatic castration-resistant prostate cancer; OS = overall survival; TTP = time to progression.
Kantoff CS, et al. N Engl J Med. 2010;363:411-422.
IMPACT OS: Primary Endpoint ITT Population Sipuleucel-T: First therapeutic cellular immunotherapy to demonstrate effectiveness in Phase III clinical trials; first FDA approved therapeutic cancer vaccine
Probability of Survival (%)
100
•
p = .032 (Cox model) HR = 0.775 [95% CI 0.614, 0.979]
•
Median Survival Benefit = 4.1 mos
•
Sipuleucel-T (n = 341) Median Survival = 25.8 mos
•
Placebo (n = 171) Median Survival = 21.7 mos
80
60 Sipuleucel-T 40 Placebo
20
0 0
12
24
36
48
60
72
Months since Randomization
ITT = intent-to-treat; HR = hazard ratio; CI = confidence interval Kantoff CS, et al. N Engl J Med. 2010;363:411-422.
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Conclusions: Vaccines • Therapeutic vaccines have been extensively studied with limited efficacy so far – Sipuleucel-T is the only FDA-approved vaccine
• Preventative vaccines for certain cancers are effective
TVEC • Talimogene laherparepvec (TVEC) – an oncolytic virus encoding human GM-CSF approved for melanoma
TVEC Directly attacks tumour cells1,2
Induces a systemic anti-tumour immune response1,2
Death of distant tumour cells
GM-CSF = granulocyte-macrophage colony-stimulating factor 1. Kaufman HL, et al. J Immunother Cancer. 2014;2:11. 2. Drake CG, et al. Nat Rev Clin Oncol. 2014;11:24–37.
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Durable Response Rates With TVEC in Advanced Melanoma Stages IIIB, IIIC, IVM1a2
Stages IVM1b, M1c2
Taken from Senzer 20091
First-line treatment
Second-line or greater
1. Senzer N, et al. J Clin Oncol. 2009;27:5763–5771. 2. Andtbacka R, et al. J Clin Oncol. 2015;33(25):2780– 2788. 3. NCT02263508. Available at: https://clinicaltrials.gov/ct2/show/NCT02263508. Accessed May 2016.
Checkpoint Inhibitors • Our immune system has many mechanisms to shut itself off to prevent it from recognizing “self” • We don’t want an overactive immune system – Autoimmunity
Blockade of PD-1 or CTLA-4 Signaling in Tumor Immunotherapy
Ribas A. N Engl J Med. 2012;366:2517-2519
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Ipilimumab with Metastatic Melanoma Phase III Trial of Ipilimumab ± gp100 Vaccine Vs. gp100 Vaccine Alone: MDX010-20
Pretreated Metastatic Melanoma (N = 676)
Ipilimumab + gp100 (n = 403)
R A N D O M I Z E
Ipilimumab + Placebo (n = 137) gp100 + Placebo (n = 136)
• Primary end point: OS • Secondary end points: ORR, DOR, PFS OS = overall survival; ORR = overall response rater; DOR = duration of response; gp100 = glycoprotein 100; PFS = progression-free survival Hodi FS, et al. N Engl J Med. 2010;363(8):711-723.
Kaplan-Meier Analysis of Survival Comparison
HR
Arms A vs C
0.68
p-value 0.0004
Arms B vs C
0.66
0.0026
A = Ipilimumab + gp100 B = Ipilimumab alone C = gp100 alone
B A C
Hodi FS, et al. N Engl J Med. 2010;363(8):711-723.
Ipilimumab Patterns of Response Screening
Week 12: Swelling & progression
Week 14: Improved
“mobile” Week 16: Continued improvement
Week 72: Complete remission
Week 108: Complete remission
(Memory)
Maggon. 2011. Available at: http://www.slideshare.net/MelanomaResearchFoundation/2014-seattle-patientsymposium-slide-deck. Accessed August 26, 2016.
13
10/25/2016
Pooled OS Analysis Including EAP Data: 4846 Patients 1.0 0.9
Median OS (95% CI): 9.5 (9.0–10.0)
Proportion Alive
0.8 0.7 0.6
3-year OS Rate (95% CI): 21% (20–22%)
0.5 0.4 0.3 0.2 Ipilimumab
0.1
CENSORED
0.0 0
12
24
36
48
60
72
84
96
108
120
120
26
15
5
0
Months Patients at Risk Ipilimumab 4846
1786
612
392
200
170
EAP = expanded access treatment protocol Schadendorf D, et al. J Clin Oncol. 2015;33(17):1889-1894.
OS Relative to Historical Data 1.0
1.0
Phase III Ipilimumab Predicted Survival (Kom Model)
Phase II Ipilimumab Predicted Survival (Kom Model)
0.8 Survival Probability
Survival Probability
0.8
0.6
0.4
0.2
0.6
0.4
0.2
0.0
0.0 0
20
40
60
80
100
Time (months)
120
0
20
40
60
Time (months)
• Historical controls – Phase II: 1278 patients in 42 cooperative group trials from 1975 to 20051 – Phase III: 3739 patients in 10 trials from 1999 to 2011 1. Korn EL, et al. J Clin Oncol. 2008;26(4):527-34.
Blockade of PD-1 or CTLA-4 Signaling in Tumor Immunotherapy Blockade of PD-1 or CTLA-4 Signaling in Tumor Immunotherapy.
Ribas A. N Engl J Med. 2012;366:2517-2519.
14
10/25/2016
PD-1 Antibodies • Nivolumab and pembrolizumab were both first approved to treat metastatic melanoma • Response rates, in general, higher than ipilimumab • Toxicities, in general, less than ipilimumab • MAJOR BREAKTHROUGH in immunotherapy and cancer in general!!!!
Pembrolizumab vs Ipilimumab in Treatment of Metastatic Melanoma RR 33.7%
RR 32.9%
RR 11.9%
Robert C et al. N Engl J Med. 2015;372:2521-2532.
Pembrolizumab vs Ipilimumab in Treatment of Metastatic Melanoma 100
90
90
80
80
70
Pembrolizumab, Q2W
60 50 40 30
Pembrolizumab, Q3W
20 10
Overall survival (%)
Progression-free survival (%)
100
Pembrolizumab, Q3W Pembrolizumab, Q2W
70 60 50
Ipilimumab
40 30 20 10
Ipilimumab
0
0 0
2
4
6
8
10
12
14
Months
6-month PFS: 2 wk: 47.3% 3 wk: 46.4% Ipi: 26.5%
0
2
4
6
8
10
12
14
16
18
Months
12-month OS: 2 wk: 74.1% 3 wk: 68.4% Ipi: 58.2%
Robert C et al. N Engl J Med. 2015;372:2521-2532.
15
10/25/2016
Studies of PD-1 Antibodies • Garon EB, et al. Pembrolizumab for the Treatment of Non-Small-Cell Lung Cancer. N Engl J Med. 2015;372:2018-2028. • Seiwert TY, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicenter, phase 1b trial. Lancet Oncol. 2016;17(7):956-965. • Borghaei H, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627-1639. • Motzer RJ, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373:1803-13. • Ansell SM, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372:311-319.
Studies of PD-1 Antibodies (cont.)
Larkin J et al. N Engl J Med. 2015;373:23-34.
Progression-Free Survival (Intentto-Treat Population) 100
NIVO + IPI (N=314)
NIVO (N=316)
IPI (N=315)
11.5 (8.9–16.7)
6.9 (4.3–9.5)
2.9 (2.8–3.4)
HR (99.5% CI) vs. IPI
0.42 (0.31–0.57)*
0.55 (0.43–0.76)*
--
HR (95% CI) vs. NIVO
0.76 (0.60– 0.92)**
--
--
Median PFS, months (95% CI)
90
Progression-free Percentage Survival of PFS (%)
80 70 60
*Stratified log-rank P
