2013-Program

Cancer Immunotherapy and Cancer Vaccines

New concepts are emerging in the use of cancer vaccines and other forms of active immunotherapy such as checkpoint inhibitors both as monotherapy and in combination therapies. These include: (a) When used as monotherapy, certain cancer vaccines and checkpoint inhibitors have been shown to extend survival without an improvement in time to progression. (b) In contrast to the use of conventional therapeutic agents, cancer vaccines can alter the growth rate of tumors, leading to extended survival. (c) Debulking of tumor with surgery, chemotherapeutic agents, radiation, and/or hormones, prior to or in combination with vaccines can lead to enhanced time to progression and potentially enhance survival. (d) Certain chemotherapeutic agents and small molecule targeted therapeutics can positively alter the effector T-cell to regulatory T-cell ratio thus providing a window of opportunity to concurrently employ cancer vaccines. (e) Certain conventional therapeutics can alter the phenotype of human tumors to render them more susceptible to T-cell–mediated lysis, thus enhancing the efficacy of active immunotherapy. (f) Cancer vaccines can be developed to target transcription factors, which drive the epithelial-to-mesenchymal transition (EMT) process, “stemness” and drug resistance. This session will describe these and other emerging concepts in cancer active immunotherapy and cancer vaccines.

Practical Considerations in Biomarker Development: Cutoff Selection Strategies

Cancer treatments are increasingly being developed along with a companion diagnostic assay that is used to select patients for treatment. For these assays, a cutoff must be identified that defines the assay result as positive or negative, with this information used in patient selection. Even for simple dichotomous DNA mutation-based tests, cutoff selection is required during development of the assay. Additional complexities in cutoff selection are the often limited information available to select a cutoff before enrollment in a pivotal study begins, and in the case where patients who test negative are unlikely to benefit, how many such patients must be treated to determine the clinical predictive value of the assay with a given cutoff. This session will describe strategies to identify and develop cutoffs for companion diagnostic assays, focusing on statistical and regulatory perspectives.

Defining Patient Benefit with Collection of Electronic Patient Outcome Data

There is increasing interest to include patient-reported outcomes (PROs) in drug development programs and labeling. There are two FDA guidance documents providing information about methods involved with developing, qualifying, implementing, and analyzing PRO data. However, a host of methodological and logistical challenges are involved with designing PRO endpoints. This session will review some of these challenges and solutions used in prior drug development programs. Recent oncology labels with PROs include Jakafi and Zytiga, and approaches used in these cases will be described. The relationship of PROs to other patient-centered outcomes, and to outcomes used in other contexts such as comparative effectiveness research and performance evaluation, will be described.

Quantifying the Burden of Disease for Individual Cancer Therapies

Jakafi (ruxolitinib), a small-molecule drug against myelofibrosis, was approved by the USFDA in November 2012. It is the first treatment approved against myelofibrosis and also the sponsor’s (Incyte) first drug to market. The case study is fascinating for a variety of reasons. The drug clinically validated a novel mechanism of action in cancer by blocking the Janus-kinases JAK1 and JAK2, and the sponsor used a rapid development pace until approval (six years after an activating mutation in JAK2 was first identified in this cancer); and, importantly the agent illustrates the use of patient-reported outcome tools as a key element in facilitating approval.

In the pivotal trials, the primary endpoint was a 35% or greater reduction in spleen volume at 24 weeks in Comfort 1, and at 48 weeks in Comfort 2. That was achieved in Comfort 1 by 42% of Jakafi-treated patients and in Comfort 2 by 29%. In addition, Comfort 1 also included a secondary endpoint based on a patient-reported outcome: the proportion of patients with a 50% or greater reduction in a score of a total of six symptoms from baseline to week 24. This was measured using a novel instrument, the modified myelofibrosis symptom assessment form (MFSAF) v2.0 diary, which Incyte developed in consultation with patients and FDA during early phase 1/2 testing. The work on the MFSAF enabled the company to develop a special assessment protocol with the FDA for the phase 3 trial and tracking by MFSAF of all the symptoms enabled “full approval.”

A small discussion group at the 2012 AAADV focused on the agent, but also the role of the FDA and disease-focused groups, such as academicians and advocates to create and perhaps catalog the actual “burden of disease” for the specific disease-affected patients. This discussion group, led by Elizabeth Thompson of Susan G. Komen for the Cure gathered enthusiasm to extend this work. It is hoped that this year’s small group can continue these efforts and develop tangible plans to define the “burden of disease” thus creating tools and opportunities for new agents and interventions to reduce this burden.

What’s to be Gained from N of 1 Clinical Trials?

Advances in genomic medicine have opened the possibility of conducting smaller, more informative clinical trials in which the drug to be tested is selected based on knowledge of the process, pathway or target most likely to be driving the growth of patient’s cancer. An extreme example of this is the “N of 1” clinical trial. This session will focus on the panelists’ experiences and perspectives on how such trials can be designed, conducted, and analyzed.

Project Data Sphere: A Universal Platform to Responsibly Share and Analyze Clinical Trial Datasets to Revolutionize Cancer Research

Project Data Sphere LLC is the universal platform to responsibly share and analyze clinical trial datasets to revolutionize cancer research. It is designed to network all stakeholders in the cancer community – researchers, industry, academia, patients, providers and other organizations – in a collaborative effort to transform “big data” into solutions for cancer patients.
Project Data Sphere makes data sharing simple and easy while addressing common concerns about security, privacy, intellectual property, cost and complexity. Project Data Sphere provides research organizations with access to deidentified individual patient-level datasets through its trusted online platform, allowing researchers to tap into and maximize the value of historic data and patient participation in clinical trials.
It takes up to $2 billion to bring a drug to market, with less than 5 percent of researched cancer compounds making it to the pharmacist’s shelf. About the same number of people are dying from cancer now as did 30-40 years ago and cancer still accounts for more deaths than heart disease, an estimated 7.6 million deaths per year.
Significant advances in “big data” management and analysis give the oncology community the capability to share cancer data on a large scale. Everyone benefits from data sharing including academics, researchers, industry, and patients. Data sharing may accelerate research by helping companies design more efficient clinical trials through: ready-made comparisons of different treatment regimens, instant pseudo-experimental control groups to study the impact of risk factors, data standards and an opportunity to use multiple instances of small sample studies to develop valid epidemiological population estimates.

Accelerating Anticancer Agent Development and Validation Workshop
2013 Program


Wednesday, May 8

7:00-8:00 am Registration/Continental Breakfast
8:00-9:00 am Opening Remarks
  • H. Kim Lyerly, M.D. ;Duke University
  • Gregory Reaman, M.D. ;U.S. Food and Drug Administration
  • Richard Schilsky, MD ;American Society of Clinical Oncology
  • Raymond DuBois, MD, PhD ;American Association for Cancer Research
  • Chandini Portteus ;Susan G. Komen for the Cure
9:00 - 10:30 am Session I: Key Issues in the Design, Conduct and Analysis of Oncology Trials
Chair: Thomas Fleming, PhD ;University of Washington
  • Challenges in the Use of Biomarkers as Endpoints in Phase 3 Trials
    Speaker: John Powers, MD; George Washington University
  • Challenges in the Development and Validation of Biomarker-based Tests for Personalized Therapeutic Decision-making in Oncology
    Speaker: Lisa McShane, PhD; National Cancer Institute
  • Confirmatory vs. Exploratory Analyses in Clinical Trials
    Speaker: Thomas Fleming, PhD; University of Washington
10:30 – 11:00 am Break
11:00 - 12:30 pm Session II: FDA Core Curriculum #1
Modules are conducted concurrently, and will be repeated on Thursday and Friday. Learners will have the opportunity to attend all three modules.
  • Module 1: Bridging the Gap Between Drug Discovery and Clinical Trials.
  • Speakers: Todd Palmby, PhD and Marc Theoret, MD
  • Module 2: Clinical Pharmacology: Finding the Right Dose for All Patients.
  • Speakers: Julie Bullock, PharmD and Stacy Shord, PharmD
  • Module 3: From Activity to Meaningful Clinical Benefit: Considerations for Clinical Development Programs to Support U.S. Marketing Approval.
  • Speakers: Paul Kluetz, MD and Tatiana Prowell, MD
12:30 - 1:30 pm Lunch
1:30 - 3:30 pm Session III: Panel Discussion: Defining and Describing "Meaningful Clinical Benefit"
Chair: Chandini Portteus ;Susan G. Komen for the Cure
Panelists:
  • Amy Abernethy, MD; Duke University
  • Thomas Fleming, PhD; University of Washington
  • Patricia Haugen; National Breast Cancer Coalition
  • Mace Rothenberg, MD; Pfizer Pharmaceuticals
  • Mary Jackson Scroggins, Pathways Project
  • Martin Stockler, MD; University of Sydney (Australia)
  • Wyndham Wilson, MD; National Cancer Institute
3:30 – 4:00 pm Break
4:00 – 5:30 pm Session IV: Case Studies #1
Case studies are conducted concurrently, and will be repeated on Thursday and Friday. Learners will have the opportunity to attend all three case studies.
  • Jakafi - Incyte Corporation (ruxolitinib phosphate)
    A kinase inhibitor indicated for treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis.
  • Perjeta – Genentech (pertuzumab)
    A HER2/neu receptor antagonist indicated in combination with Herceptin® (trastuzumab) and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.
  • Xtandi – Medivation, Inc./Astellas Pharma US (enzalutamide)
    An androgen receptor inhibitor, indicated for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously received docetaxel.
5:30 – 7:30 pm Reception/Dinner/Dinner Panel
Panel: Alternate Models for Oncology Drug Discovery and Development
Chair: Jacqueline Northcut ,Texas BioAlliance
Panelists: Kald Abdallah, MD, PhD; Sanofi, US
Philip Jones, MD; MD Anderson Cancer Center
David Schubert, MBA; Houston Area Translational Research Consortium

Thursday, May 9

7:30 - 8:00 am Continental Breakfast
8:00 - 9:00 am Session V: Breakthrough Therapies
Chair: Gregory Reaman, MD; U.S. Food and Drug Administration
Moderator: Richard Pazdur, MD; U.S. Food and Drug Administration
Introduction: Gideon Blumenthal, MD; U.S. Food and Drug Administration
  • Novartis Pharmaceuticals Corp.
  • Speaker: Margaret Dugan, MD
  • Pharmacyclics, Inc.
  • Speaker: Lori Kunkel, MD
  • Merck Research Laboratories.
  • Speaker: Eric Rubin, MD
9:00 - 10:30 am Session VI: Incorporating Integral Genomic Testing in Clinical Trials
Chairs: Helen Chen, MD and Barbara Conley, MD ; National Cancer Institute
  • Assays and Devices
    Speaker: Mickey Williams, MD; National Cancer Institute
  • Implementation of Clinical Trials
    Speaker: Lillian Siu, MD; Princess Margaret Hospital (Canada)
  • Regulatory Considerations
    Speaker: Robert Becker, MD; U.S. Food and Drug Administration
10:30 - 11:00 am Break
11:00 am – 12:30 pm Session VII: FDA Core Curriculum #2
  • Module 1: Bridging the Gap Between Drug Discovery and Clinical Trials.
  • Speakers: Todd Palmby, PhD and Marc Theoret, MD
  • Module 2: Clinical Pharmacology: Finding the Right Dose for All Patients.
  • Speakers: Julie Bullock, PharmD and Stacy Shord, PharmD
  • Module 3: From Activity to Meaningful Clinical Benefit: Considerations for Clinical Development Programs to Support U.S. Marketing Approval.
  • Speakers: Paul Kluetz, MD and Tatiana Prowell, MD
12:30 – 1:30 pm Lunch
1:30 – 3:00 pm Session VIII: Case Studies #2
  • Jakafi - Incyte Corporation (ruxolitinib phosphate)
  • Perjeta – Genentech (pertuzumab)
  • Xtandi – Medivation, Inc./Astellas Pharma US (enzalutamide)
3:00 – 3:30 pm Break
3:30 – 5:30 pm Session IX: In-depth Discussion Groups
  • Cancer Immunotherapy and Cancer Vaccines
    Chairs: H. Kim Lyerly, MD; Duke University
    Jeffrey Schlom, MD; National Cancer Institute
    Speaker: James Gulley, MD; National Cancer Institute
    Robert Le, MD, PhD; U.S. Food and Drug Administration
  • Practical Considerations in Biomarker Development: Cutoff Selection Strategies
    Chairs: Eric Rubin, MD ;Merck Research Laboratories and Thomas Fleming, PhD ;University of Washington
    • Introduction and Overview
      Speaker: Eric Rubin, MD; Merck Research Laboratories
    • Statistical Approach to Selection of Cutoffs for Biomarkers
      Speaker: Lisa McShane, PhD; National Cancer Institute
    • Regulatory Perspectives to Selection and Confirmation of Cutoffs for Biomarkers
      Speaker: Elizabeth Mansfield, PhD; U.S. Food and Drug Administration
  • Defining Patient Benefit with Collection of Electronic Patient Outcome Data
    Chairs: Chair: Ethan Basch, MD ;University of North Carolina, Chapel Hill
    Speakers: Amy Abernethy, MD; Duke University
    Ashley Slagle, PhD; Oak Ridge Institute for Science and Education
    Tina Staley, LCSW; Pillars of Life, Inc.
    Tina Staley, LCSW; Pathfinders
  • Quantifying the Burden of Disease for Individual Cancer Therapies
    Chair: Gwen Darien ;Pathways Project
    Panelists: Laurie Burke, RPh, MPH; U.S. Food and Drug Administration
    Brandon Hayes-Lattin, MD; LiveStrong
    Martin Stockler, MD; University of Sydney (Australia)
  • What’s to be Gained from N of 1 Clinical Trials?
    Chair: Mace Rothenberg, MD (Pfizer Pharmaceuticals)
  • Project Data Sphere: A Universal Platform to Responsibly Share and Analyze Clinical Trial Datasets to Revolutionize Cancer Research
    Chair: Kald Abdallah, MD, PhD; Sanofi, US
5:30 – 7:00 pm Reception
Friday, May 10
7:30-8:00 am Continental Breakfast
8:00 - 9:30 am Session X: Combinations between Targeted Agents: Promise, Opportunities and Challenges
Chairs: Raymond DuBois, MD, PhD ;American Association for Cancer Research, and Richard Schilsky, MD ;American Society of Clinical Oncology
  • Target Selections for Combination Strategies
    Speaker: Levi Garraway, MD, PhD; Harvard Medical School
  • Early Phase Clinical Development of Targeted Drug Combinations
    Speaker: Lillian Siu, MD; Princess Margaret Hospital (Canada)
  • Success and Failures in Late Phase Clinical Development
    Speaker: Josep Tabernero, MD, PhD; Valle d’Hebron University Hospital (Spain)
9:30 – 10:00 am Break
10:00 – 11:30am Session XI: FDA Core Curriculum #3
  • Module 1: Bridging the Gap Between Drug Discovery and Clinical Trials.
  • Speakers: Todd Palmby, PhD and Marc Theoret, MD
  • Module 2: Clinical Pharmacology: Finding the Right Dose for All Patients.
  • Speakers: Julie Bullock, PharmD and Stacy Shord, PharmD
  • Module 3: From Activity to Meaningful Clinical Benefit: Considerations for Clinical Development Programs to Support U.S. Marketing Approval.
  • Speakers: Paul Kluetz, MD and Tatiana Prowell, MD
11:30 am – 12:00 pm Box Lunches
12:00 – 1:30 pm Session XII: Case Studies #3
  • Jakafi - Incyte Corporation (ruxolitinib phosphate)
  • Perjeta – Genentech (pertuzumab)
  • Xtandi – Medivation, Inc./Astellas Pharma US (enzalutamide)
1:30 pm Adjourn