CURE OM Patient Registry Update - 2019 CURE OM Symposium
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CURE OM Patient Registry Update - 2019 CURE OM Symposium
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Dr. Richard Carvajal gives an update on the development of the CURE OM Patient Reported Ocular Melanoma Registry.
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CURE OM Patient Registry Update - 2019 CURE OM Symposium
- 1. CURE OM Patient-Powered Registry: Capturing Patient Reported Real World Data to Improve Ocular Melanoma Outcomes
- 2. Messages from our Patients and Caregivers… Support Hope Advocacy Research Partnership Collaboration Community Education
- 3. CURE OM Patient Powered Registry Patient Registry • Organized system that uses observational study methods to collect uniform data to evaluate specified outcomes for a defined population that serves a predetermined purpose Overall Objective: To build a patient developed and led registry of prospectively collected real world data that can be utilized by all stakeholders to generate the real world evidence necessary to improve outcomes for those affected by ocular (uveal and conjunctival) melanoma Real World Evidence • Evidence derived from real world data through the application of research methodology Stakeholders • Patients and family members • Clinicians • Researchers • Pharmaceutical companies • Regulatory agencies • Payers
- 4. Swift et al. Clin Transl Sci (2018) 11, 450-460. • Data relating to patient health status and/or the delivery of heath care • Sources: EMR, admin and claims data, home monitoring devices, wearable technologies, patient registries, clinical trials Real World Data
- 5. What is a Patient-Powered Registry? To focus research more directly on patient and family member needs, patient and family advocates and organizations have created and operated “patient-powered” patient registries since as early as 1995. These registries are distinguished from researcher-generated registries in that the registry and the research it yields is managed by patients and family members themselves, often through a disease advocacy organization that receives advice and input from a scientific board of advisors. AHRQ: Engaging Patients in Information Sharing and Data Collection: The Role of Patient-Powered Registries and Research Networks 5
- 6. Emerging Emphasis Upon RWE Dec 2018 March 2019
- 7. Benefits of a Patient-Reported Registry Share data with all parties – patients, clinicians, researchers, providers, partner organizations and industry Data obtained directly from the patient or his/her legally authorized representative Data entered from anywhere in the world Brings together the patient population – platform for uniting patients around the world Enhances patient education and understanding of disease Acts as a vehicle for the patient community’s voice – patients, family members and caregivers become an integral voice in research Patients can relate, compare and learn from other patients’ journeys Helps patients, their families and caregivers further understand their condition so they can take a more active role in their care and advocacy Patient Benefits
- 8. Benefits of a Patient-Reported Registry Share data with all parties – patients, clinicians, researchers, providers, partner organizations and industry Real world data Act as a single source of information that records the patient’s full journey with OM Supports fundamental epidemiological research Documents geographic practice variations Document patient preferences Supports health and social services planning Post-marketing surveillance Demonstrates value Benefits to OM Research
- 9. Real World Evidence & Drug Reimbursement: The 4th Hurdle Quality Safety Efficacy Value For regulatory approval (FDA, EMA) For reimbursement (NICE, HTA)
- 10. • The availability of real world contemporary outcomes data would aid in the development of more robust biostatistical trial designs • Optimal trial methodologies for demonstration of efficacy and safety in rare tumors may differ from those used in more common conditions. • Real world contemporary outcomes data may be used to support the use of novel study designs that: – Are acceptable to the regulatory authorities; – Minimize the number of individuals treated on control arms with limited efficacy; and, – Permit those randomized to a control arm earlier access to the investigational therapy. Real World Evidence & Clinical Trial Development
- 11. IMCgp100 Program Registration Strategy Accelerated approval strategy: Single arm trial approval strategy is based on either ORR or OS with RWE as comparator IMCgp100-102: Second or third line in the metastatic setting IMCgp100 at RP2D from Ph I N ~ approx 150 Interim Analysis Final Analysis Real World Evidence (ORR, OS via one of three platforms: Meta- analysis, global patient registry or Flatiron derived comparator) Opportunities for approval IMCgp100-202: First line metastatic setting R Investigator Choice (dacarbazine, pembrolizumab or ipilimumab) N = approx 109 Sample size Interim Analysis Final Analysis re-estimation Primary endpoint: Median OS Traditional approval strategy: Randomized study of IMCgp100 v. Investigator choice with OS as endpoint IMCgp100 at RP2D from Ph I N = approx 218 Opportunities for approval
- 12. Timeline of Registry Activities March 2016 CureOM Unite Campaign Launch Hired Registry Expert Consultant Formed Interdisciplinary Steering Committee March 2017 First Steering Committee Working Group Meeting Engaged and Surveyed Stakeholders; Identified Funding Sources Formalized Registry Objectives and Protocol Vetted Multiple Technology Platforms and Innovation Models Nov 2018 Formally Presented Proposal to MRF SAC Progress towards Seed Funding March 2019 Second Steering Committee Working Group Meeting
- 13. Interdisciplinary Steering Committee Patient/Family Advocates Linda O’Brien Chad Kimbler, MA Carla Tressel Shana Ratner, MD Ocular Oncologists Bertil Damato, MD, PhD Dan Gombos, MD Ivana Kim, MD Miguel Materin, MD Medical Oncologists Richard Carvajal, MD Marlana Orloff, MD Nursing Renee Zalinsky, RN Barbara Perez, BSN, RN Social Work Alison Petok, MSW, MPH Melanoma Research Foundation CureOM Sara Selig, MD, MPH Jacqueline Kraska Biostatistics Codruta Chiuzan, PhD Patient Reported Outcomes Ethan Basch, MD, MSc Epidemiology Ashley Schoenfisch, PhD
- 14. Overall Objectives 1. To develop and utilize a standardized global patient-reported online registry to provide data regarding the incidence, prevalence, demographics, risk factors, genetics, natural history, treatments and patient experience (patient preferences and quality of life) from diagnosis through the lifetime of OM. 2. To provide patient centered data to enhance the care of individuals with OM. 3. To facilitate collaborative efforts between patients, clinicians and researchers to improve the outcomes for patients affected by this disease. 4. To develop a virtual OM biospecimen repository (future goal).
- 15. Eligibility and Enrollment Targets Recruitment: Start in the United States Over time, achieve global coverage, starting with international collaborators in UK, Canada, Europe and Australia Enrollment target of 400 recruits annually (1,200 over the first 3 years) Inclusion Criteria: Diagnosis of OM Ability to provide informed consent Exclusion Criteria: No conclusive diagnosis of OM
- 16. CURE OM Patient Registry Experience Inform and Engage Register Consent Complete Profile Knowledge
- 17. Recent Accomplishments Added three new disciplines to interdisciplinary registry steering committee: Biostatistics, Epidemiology, and Patient-Reported Outcomes experts. Secured transformational funding partnership to support support launch and multiyear maintenance. Opened new partnership opportunities including funding partners as well as international participants. Presented and engaged stakeholders and partners at three international scientific meetings. – Including obtaining feedback from a wide range of stakeholders as well as an oral presentation at the 2019 International Society of Ocular Oncology meeting.
- 18. Registry of registries… Academic Natural History Registry
- 19. • Demographics • Family history • Social history • Con meds • Diagnostic procedures/results • Therapeutic procedures/results • Pathology results • Molecular results • Laboratory results • Imaging results • Surveillance strategies • Treatment/Toxicity • Biospecimen repository • Symptoms • Quality of life • Diet/supplements • Lifestyle/Fitness/Stress • Environmental exposures • Occupational exposures • Impact upon daily life • Perception of disease • Perception of treatments • Treatment effectiveness • PRO-CTCAE • Economic impact • Ratings of care Academic Registry Patient Registry Relationship Between Registry Efforts
- 20. Next Steps 1. Confirm technology partner 2. Finalize data dictionary 3. Build platform 4. Obtain IRB approval 5. Continue outreach, education and fundraising efforts 6. Launch!!!
- 21. Thank you
Editor's Notes
- Passed away July 2018 Jim Mills Ashley McCrary Cassie Beisel
- Patient registry: Uniform data – clinical and other Defined population – disease, condition, exposure Predetermined purpose – scientific, clinical or policy
- NICE = national institute for health and care excellence (HTA in England and Wales) VALUE BASED PRICING
- Although it is commonly estimated that 20 to 25% of all oncology patients have a rare cancer diagnosis, with our evolving understanding of cancer biology and the associated changes in our taxonomy of malignancy, these numbers now underestimate the incidence of rare malignancies. Our ability to effectively manage and treat individuals with these conditions requires a thorough understanding of the natural history and the pathophysiology of these diseases, as well as a re-evaluation of how we develop novel therapies for rare cancers. It is acknowledged by the regulatory authorities that certain aspects of drug development that are feasible for common diseases may not be feasible for rare diseases; however, regulatory approval of all drugs, regardless of the rarity of the indication, requires the demonstration of substantial evidence of effectiveness and safety. Given the inherent challenges associated with drug development for uncommon conditions, the optimal methodologies available for demonstration of efficacy and safety in rare tumors may differ from those used in more common conditions. The development of real world contemporary outcomes data for rare cancers in parallel to the conduct of pivotal trials in those indications may be used to support the use of novel study designs that are acceptable to the regulatory authorities, minimize the number of individuals treated on control arms with limited efficacy, and/or permit those randomized to a control arm earlier access to the investigational therapy. In this application, we propose to develop a multicenter prospective natural history study that will provide such data for uveal melanoma, a rare malignancy that is clinically and biologically distinct from its more common cutaneous counterpart, which qualifies as an orphan disease as defined by the United States Food and Drug Administration (FDA), and for which no therapy that improves outcomes once distant metastases occurs has been identified. We have specifically partnered with Immunocore, a biotechnology company focused on the development of a new class of immunotherapeutic agents, to create a prospective natural history study to support the development of IMCgp100, a novel bispecific biological agent that was granted Orphan Drug Designation by the FDA in January 2016 (IND 114,314; Lead Medical Reviewer, Marc Theoret; Project Manager, Gina Davis), for patients with metastatic uveal melanoma. Recent interactions between Immunocore and the European Medicines Agency have outlined a development strategy of a pivotal randomized study in the first line setting of uveal melanoma (IMCgp100-202) that mandates the use of existing real world registry data for the purposes of providing overall survival data to permit contextualization of trial results. Regulatory approval for IMCgp100 would lead to the first approved agent available for the treatment of metastatic uveal melanoma. Our proposed natural history program will provide the real world registry overall survival data necessary for this development program. Furthermore, the data our program will generate can be used to support registration strategies of other novel agents beyond IMCgp100 that are in development for the treatment of this disease. This application has been developed together with co-investigators from 20 major uveal melanoma centers within the United States. We are collaborating with international leaders in the field who are developing uveal melanoma registries for the United Kingdom/Europe and Australia, as well as leadership from the Melanoma Research Foundation CureOM patient advocacy group which is developing an online database for patient-entered data, with the intent to harmonize our efforts to permit the utilization of data from all four efforts for joint analysis. The completion of this proposal with result in the identification of benchmark endpoints for the development of novel therapies for uveal melanoma, will inform critical outstanding questions in the field unlikely to be answered by well-designed prospective clinical trials, and will result in a virtual uveal melanoma tumor repository that can be utilized by investigators to develop or confirm hypotheses related to tumor biology and to facilitate drug development for this deadly disease. The specific aims of our proposal include: Specific Aim 1: To document clinical outcomes of patients with uveal melanoma, adjusting for known prognostic risk factors as well as other baseline demographic and clinical factors, including therapies, in order to provide benchmark endpoints for the development of novel therapies for this disease. Specifically, we will provide overall survival data from our existing real world registry requested by the European Medicines Agency to support the development of IMCgp100 (IND 114,314). Specific Aim 2: To inform critical outstanding questions in the field unlikely to be answered by well-designed prospective clinical trials regarding risk stratification, radiographic surveillance, and optimal patient selection for liver-directed as opposed to systemic therapies. Specific Aim 3: To develop a virtual uveal melanoma tumor repository that can be utilized by investigators to develop or confirm hypotheses related to tumor biology and to facilitate drug development.
- The intra-patient escalation regimen of IMCgp100 results in an approximate 50% increase in dose above the dose identified in the FIH Phase 1 study, manageable safety profile and observations of efficacy in patients with metastatic UM Prolonged overall survival in this single arm trial is associated with observed toxicities and immune response in patients, including more severe skin toxicity, reductions in mean arterial pressure and lymphocyte trafficking with the first 3 weekly doses of IMCgp100 as well as a potent IL-6 response at 24 hours after the first dose Objective response rate of 18% was observed in the Phase 1 portion of the trial and the median OS in this patient cohort has not been reached with a median follow-up of 19.1 months. Objective responses were observed and RECIST imaging was converted to the time-based endpoint of AUC over 6 and 12 months. A preliminary association of the AUC analysis with overall survival was observed A Phase 2 expansion cohort enrolling patient with prior treatment and separate pivotal trial of IMCgp100 in advanced UM are ongoing The primary objective is to compare the OS in patients treated with IMCgp100 monotherapy versus Investigator’s Choice in HLA-A*0201 positive patients with advanced UM with no prior treatment in the metastatic setting. The secondary objectives of the study are: • To characterize the safety and tolerability of IMCgp100 in the intrapatient dose escalation regimen • To characterize the pharmacokinetic (PK) profile of single-agent IMCgp100 in the intra-patient dose escalation regimen • To assess the objective response rate (ORR) between IMCgp100 and Investigator’s Choice using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 response criteria • To assess the anti-tumor efficacy of IMCgp100 with the parameters of ORR, progression free survival (PFS), duration of response (DOR), and disease control rate (DCR) • To evaluate the treatment and disease impact to health-related quality of life (HRQoL) in patients treated with IMCgp100 versus patients treated with Investigator’s Choice. HRQoL will be assessed using 2 established patient reported outcome instruments: o The EuroQoL-5 Dimensions – 5-levels of disease severity scale (EQ-5D,5L) to enable an assessment of health status compared to population norms o The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 to provide an insight into domains of cancer-specific patient health • To evaluate the incidence of anti-IMCgp100 antibody formation following multiple infusions of IMCgp100 in the intra-patient dose escalation regimen This is an open-label, randomized, multi-center Phase II study of IMCgp100 versus Investigator’s Choice (dacarbazine, ipilimumab, or pembrolizumab) in adult (> 18 years) in HLA-A*0201 positive patients with advanced UM previously untreated in advanced or metastatic setting. In this study, IMCgp100 is administered on a weekly basis with an intra-patient escalation dosing regimen compared with limited Investigator’s Choice at the approved doses of these agents. Patients enrolled in the study will be randomized in a 2:1 ratio (IMCgp100:Investigator’s Choice) and stratified by lactate dehydrogenase status to receive either IMCgp100 (Arm 1) in the intra-patient escalation dosing regimen or Investigator’s Choice (Arm 2) at the approved dose every 3 weeks of a 21-day cycle. The sample size of the trial is planned at 327 patients with advanced UM randomized in a 2:1 ratio to IMCgp100 (n = 218) or Investigator’s Choice (n = 109). Three analyses will be performed using a 3-stage adaptive group sequential design. • The first analysis will re-assess sample size using conditional power • The interim analysis will include an assessment of all relevant clinical outcomes to include OS, progression-free survival, and overall response rate • The final analysis
- Ashley Schoenfisch Sara M. Selig, MD, MPH Director, CURE OM Melanoma Research Foundation Associate Physician, Brigham and Women's Hospital Instructor, Harvard Medical School Associate Director, COPE Program Director of US Engagement, Partners in Health Bertil Damato, MD, PhD, FRCOphth Ocular Oncologist Professor of Ophthalmology and Radiation Oncology, Oxford University, United Kingdom Dan S Gombos, MD, FACS Ocular Oncologist Professor & Chief Section of Ophthalmology Department of Head & Neck Surgery MD Anderson Cancer Center Houston Texas USA Ivana Kim, MD Ocular Oncologist Associate Professor of Ophthalmology, Harvard Medical School, Co-Director Ocular Melanoma Center, Massachusetts Eye and Ear Infirmary Miguel A. Materin, MD Ocular Oncologist Duke University Eye Center Professor of Ophthalmology Director, Ophthalmic Oncology Rich Carvajal, MD Medical Oncologist Associate Professor of Medicine Director of Melanoma Service Director of Experimental Therapeutics Columbia University Medical Center Marlana Orloff, MD Medical Oncologist Assistant Professor Department of Medical Oncology Thomas Jefferson University Hospital Renee M. Zalinsky, RN, OCN Senior Cancer Care Coordinator Metastatic Uveal Melanoma Navigator/ Senior Cancer Care Coordinator Sidney Kimmel Cancer Network at Jefferson University Hospital Linda O’Brien Patient (Primary Disease) 9 years NED (No Evidence of Disease) Barbara Perez, BSN, RN Research Nurse Specialist, Ocular Oncology University of Miami Health System Chad Kimbler, BSBA, MA Patient (Primary Disease) I was diagnosed at age 29, my genetic testing revealed Castle Class 2. I am currently on a 3-month scan scheduled and am metastatic free. My favorite past time is exploring the friendly skies, I am a private pilot, but haven't been up since my encounter with Ocular Melanoma. Carla Tressel Patient (Metastatic Disease) Patient diagnosed with choroidal melanoma in August 2004 at the age of 44. I was diagnosed with metastases to my liver in January 2013. I stopped working in July of 2014 to concentrate on my health and to spend quality time with my husband, James. Shana Ratner, MD Daughter and Internist Family Member of OM Patient Alison Petok, MSW, LCSW, MPH Social Worker, Department of Medical Oncology Sidney Kimmel Cancer Center Thomas Jefferson University
- The MRF’s CURE OM Patient-powered and patient-reported registry will capture comprehensive information on genetics, disease characteristics, environment, types of treatments, physical outcomes and quality of life. Patient data from the registry will be used to unite the OM patient population, support and drive OM research, inform and educate the patient community and its partners, and engage all invested sectors to advance treatments and find a cure, including academia, healthcare and industry. It will also inform research initiatives focused on policy, patient preferences and standards of care. The registry will be a critical tool for leveraging patient input, engaging patients in the research process and improving outcomes.
- STEP 1: Learn about registry study – Inform & Engage STEP 2: Register – create online account with registry STEP 3: Informed consent online – consent to terms & conditions of participating in study STEP 4: Take registry study surveys STEP 5: See results of data