REMMIT Study Evidence-based analysis for targeted treatment

What is REMMIT

The Refractory Metastatic Mechanism Informatics Based Treatment study (REMMIT) will match each person fighting advanced metastatic cancer to a combination of therapies customized to the genomic and non-genomic changes causing their disease to progress. Simply, individualized medicine. For many patients, the standard of care that was approved 8-10 years ago is not enough.

REMMIT is based on the dramatic clinical results of customized combination therapy in metastatic breast and ovarian cancer demonstrated by Razelle Kurzrock, MD, of the University of California, San Diego Moore Precision Cancer Center and Brian Leyland-Jones, MD, director of the Avera Precision Oncology Center at the Avera Health System.

WHAT WE WILL DO FOR YOU

  • REMMIT will provide 2,000 cancer patients and their physicians with combination treatments over the next 2-3 years.
  • Every cancer-fighting person who participates in REMMIT will be genomically tested and given treatment that is customized or personalized to the way their tumor cells develop. While cancer cells may originate in one part of the body, they often kill when they spread. We will not turn away any physician or patient because they don’t have cancer in a specified body part or location.
  • To this end, REMMIT will involve people whose cancer cells are multiplying even after one round of traditional treatment and who are able and willing to provide tumor tissue and other samples needed for customization and monitoring
  • Every cancer-fighting person will get the combination of treatments they deserve. They and their friends and family will get the care they deserve. Their physicians will be able to learn from and contribute to the well-being of thousands of other patients without having to spend more time and money on health IT. Our goal is to raise the money to fund the patient’s cost for the trial.
  • The ultimate goal is to add as much life and well-being to each person, the same way that it has for people with AIDS and hepatitis C: through combinations of medicines that anticipate and control how cancer cells survive.

Why? It’s necessary to improve cancer survival for three reasons:

  1. 1Cancer is perhaps the most complex and evasive disease, we need to collect all types of relevant data for one person, as frequently as possible — perhaps every day or periodically over months or years and then aggregate and use this information to continually improve or change treatments for every cancer patient.1
  2. 2Treatment combinations will need to be personalized to be effective; traditional clinical trials that randomize subjects to one combination or to standard of care are both unscientific and inefficient.
  3. 3Patients deserve the right combinations of treatments immediately to treat their illness. REMMIT will collect data that will allow health plans and insurers to cover such treatments and evaluate the financial impact this approach has on themselves and patients.

REMMIT is a VOICE for patients, their families and caregivers. As a “patient first” defined study, REMMIT will provide people fighting cancer a role in determining what quality of life outcomes should be studied and how data should be shared.

With the help and guidance of people fighting cancer, REMMIT will treat participants as valued partners. It will reduce the time, cost, and inconvenience associated with traditional clinical trial participation by allowing people to share data remotely, through health apps; be seen by their nurse or physician in their home, if desired; and helping out with supportive services.

For more information, contact Robert Goldberg, bob@drbobgoldberg.com

Brian Leyland-Jones, MB BS, PhD

Professor Leyland-Jones is an internationally renowned breast cancer expert, a Visiting Scholar for the Division of Oncology at Stanford University School of Medicine, and Vice-President of Molecular and Experimental Medicine at the Avera Cancer Institute.

Prof. Leyland-Jones was most recently Director of Edith Sanford Breast Cancer Research in Sioux Falls. He came to Sioux Falls from Atlanta, Ga., where he was Executive Vice-President and Director of the Winship Cancer Institute and Chair of Hematology-Medical Oncology at Emory University School of Medicine. Prof. Leyland-Jones lead the Centre to obtain National Cancer Institute Cancer Centre Designation, the first in the State of Georgia, and for the first time in 30 years. He was named both the Georgia Research Alliance Eminent Scholar and Georgia Cancer Coalition Distinguished Cancer Scholar.

Dr. Leyland-Jones earned biochemistry, medical and PhD degrees from the University of London. After postgraduate training in London, he completed fellowships in medical oncology and clinical pharmacology at Memorial Sloan-Kettering Cancer Center and Cornell University Medical College, and then went become Assistant Professor in both disciplines at both institutions. Dr. Leyland-Jones subsequently served as head of the Developmental Chemotherapy Section at the National Cancer Institute, and then founding Chairman of the Department of Oncology, Minda de Gunzburg Chair in Oncology, Professor of Medicine and Oncology, and Director of the McGill Comprehensive Cancer Center at McGill University in Montreal, Canada.

He has over 35 years’ experience in oncology, molecular and clinical pharmacology: his whole life has been devoted to the development of a broad spectrum of novel therapeutic approaches, and associated biomarkers. His major contributions have been specifically in the areas of platinum, anthracyline, taxane. trastuzumab, erythropoiesis-stimulating agents, mTOR/ IGF1R clinical trials, preclinical models and clinical/ molecular pharmacology. He has been responsible for coordinating biospecimen collection guidelines globally and has built a CLIA facility for biomarker profiling. He is also deeply involved with IBCSG, BIG and iSPY2 trials and formerly coordinated the ECOG Breast Molecular Profiling Working Group. His more recent focus has been the application of combined array/ sequence profiling to large retrospective cooperative group and intergroup trial sets with the goal of determining key drivers and parallel pathways, and the application of this knowledge to Forward Genomic oncology trials.

Dr. Leyland-Jones is the recipient of numerous research grants, and has served as principal, co-principal and co-investigator on more than 100 clinical studies. He has authored and co-authored more than 200 peer-reviewed articles and book contributions, 28 books and book chapters, 354 abstracts and 34 patents.

Razelle Kurzrock, MD

Dr. Razelle Kurzrock is known for developing the largest Phase 1 clinical trials department in the nation/world while at the University of Texas M.D. Anderson Cancer Center. A central theme of that program was the personalized medicine strategy, embodied in a protocol called PREDICT for Profile-related Evidence Determining Individualized Cancer Therapy. This approach utilized advanced molecular technologies to match patients with targeted cancer treatment that is more likely to work for their individual tumors.

At Moores Cancer Center, Dr. Kurzrock’s charge is broad, including not just growing and innovating the center’s clinical trials program, but also heading its newly established Center for Personalized Cancer Therapy. This center focuses on precision medicine trials, using the most innovative genomically-targeted drugs and/or agents that arm the immune system. As a physician-scientist, Dr. Kurzrock brings extraordinary expertise and experience in clinical research, business operations, regulatory operations, financial and budget planning, and administrative oversight, in addition to her world-recognized work in translational science. Dr. Kurzrock is also Chief of the Division of Hematology and Oncology in the UC San Diego School of Medicine. Dr. Kurzrock received her MD degree from the University of Toronto and has over 600 peer-reviewed publications and a uniquely strong record of competitive grant funding within the setting of Phase I program building.

Dr. Kurzrock also has a strong history of building outstanding education/training programs. At University of Texas MD Anderson Cancer Center, she founded and directed the MS/PhD program (degree granting) in Human Biology and Patient-Based Research, as well as the Fellowship in Investigational Cancer Therapeutics. At UCSD Moores Cancer, she founded and directs the Fellowship in Personalized Cancer Therapy.

Dr. Kurzrock has four children and lives with her husband, Dr. Philip Cohen, a dermatologist, in San Diego, CA.

VALUE OF SEQUENCING-GUIDED TREATMENT FOR PATIENTS WITH ADVANCED MALIGNANCIES

C Williams, B Goldberg, K Williams, P De, L Rojas, D Starks, N Dey, J Klein, R Elsey, A McMillan, B Xu, P Ye, B Solomon, A Krie, B Leyland-Jones; Avera Center for Precision Oncology, Avera Cancer Institute, Sioux Falls, SD; Center for Medicine in the Public Interest, New York, NY

Background

  • Current approaches in the treatment of advanced cancer are based predominantly upon lessons learned from the cytotoxic era. Our current approaches have yielded incremental steps forward, but most patients who develop metastatic disease still die and the costs of care are soaring
  • Rational combination approaches that are selected based upon computational analysis of multi-platform molecular data, tailored for each patient based upon their past medical history, performance status and unique molecular profile, and curated to prevent the development of resistance represent a possible solution that warrants further exploration
  • The optimal treatment strategy for patients with advanced breast or ovarian cancer is currently unknown. Resistance to standard therapies like anthracyclines and taxanes limit the number of treatment options in many patients to a small number of non-cross-resistant regimens
  • We hypothesized that genomic and proteomic profiling of samples from advanced patients would identify genomic alterations that are linked to targeted therapies, and that this could facilitate a personalized approach to therapy for our patients

Methods

  • Single center analysis of 150 advanced breast or ovarian cancer patients seen over a 24 month period (May 2014 through April 2016)
  • Most patients were re-biopsied after consultation with the genomic oncology service
  • Most tissue samples were sent for FoundationOne© and/or TheraLink© (proteomics) and blood samples were sent for Guardant360© starting in the summer of 2015
  • All metastatic biopsies were obtained at same center (Avera Cancer Institute) and same protocol was used for all samples
  • Routine pathology was completed predominantly at Avera, including IHC and FISH for HER2 if applicable
  • All FFPE samples sent to Foundation Medicine and Theranostics were obtained and processed based upon instructions from both companies
  • All patients were enrolled in a sequencing protocol (NCT02470715) with no standardized treatment provided
  • All treatment suggestions were made by a formal sequencing review team
  • Response rates were based upon RECIST 1.1 measurements whenever possible

Results

  • 100 Evaluable patients
  • Over 60% of patients were able to receive full recommended therapy
  • Average lines of previous therapy was over 3
Table 1. Best Response Rate for Fully Evaluable Patients
Full
(n = 61)
Partial
(n = 12)
None
(n = 27)
CR 20% 8% 8%
PR 35% 42% -
SD 39% 25% 24%
PD 6% 25% 68%
CBR 94% 75% 32%

Full - patient received all of recommended therapy Partial - patient received at least 1 of the recommended therapies, CR – no detectable disease PR – greater than 30% disease reduction SD – overall no or minimal change PD - progressive disease Clinical Benefit Rate (CBR) = CR + PR + SD

Results

Results

Discussion

  • Molecular profiling patients with advanced breast or ovarian cancer has yielded actionable targets in a majority of cases
  • Presently, we are predominantly using FDA approved drugs in combinations based upon the molecular and proteomic information and seeking insurance approval for the treatment
  • Biggest challenge has been working with insurance companies to grant approval for off-label treatments/combinations
  • Our remarkable initial data provides very strong evidence that it is critical to incorporate multi-platform profiling as early as possible (preferably at diagnosis) in the disease course to allow for the best chance of benefit
  • Off-label drug use in a variety of combinations can be utilized safely and effectively in a community cancer center and make a significant impact in patient outcomes

Acknowlegments

The investigators would like to thank all of the patients, research staff, clinic nurses, and our many colleagues for their continued support of this research and the excellent care they provide our patients.

The investigators would also like acknowledge the generous support from the Helmsley Trust Foundation as well as the Fred and Pamela Buffett Cancer Center through The Leona M. & Harry B. Helmsley Charitable Trust Grant #2012PG-RHC031.