The SWOG ITSC Pilot Awards: Request for Application 2018 Announcement

Transcription

1 The SWOG ITSC Pilot Awards: Request for Application 2018 Announcement SWOG formed an alliance with two premiere basic science research institutions - Cold Spring Harbor Laboratory (CSHL) and The Jackson Laboratory (JAX) to promote the integration of ground-breaking basic research into clinical trials. SWOG is a group member of the National Cancer Institute-supported National Clinical Trials Network (NCTN), with a mission to improve the practice of cancer medicine in preventing, detecting, and treating cancer, and to enhance the quality of life for cancer survivors, primarily through design and conduct of clinical trials. Cold Spring Harbor Laboratory is an independent nonprofit research institution committed to exploring the molecular basis of human cancer through a focused, multidisciplinary approach, and using this knowledge to improve the diagnosis and treatment of all major forms of cancer. The Jackson Laboratory is an independent, nonprofit organization, focused on mammalian genetics research, which applies its strengths in genomics, preclinical modeling, and computational analytics to address the molecular pathways that drive cancer initiation, progression and resistance to therapy. Both CSHL and JAX are NCI-designated Cancer Centers. Working together, SWOG, CSHL, and JAX received seed grant funding from the NCI in 2014 to support an Integrated Translational Science Center (ITSC) with the goal of facilitating incorporation of translational science into NCTN clinical trials. The SWOG ITSC program is under the leadership of three co-principal Investigators: Dr. David Tuveson (CSHL Professor and Cancer Center Deputy Director), Dr. Edison Liu (JAX President, CEO and Cancer Center Director) and Dr. Laurence Baker (University of Michigan Professor, and Chair-Emeritus of SWOG). The mission of the ITSC is to bridge the gap between the laboratory and the clinic by elucidating the key clinical problems and challenges in oncology that can be addressed in the laboratory, discovering new diagnostic and therapeutic approaches that can be integrated into clinical trials, and providing a conduit for clinical trial results to be re-interpreted in the laboratory, identify basic research programs with potential clinical value and integrate these approaches into ongoing and developing clinical trials. The purpose of the SWOG ITSC Pilot Awards is to stimulate collaborative translational research among our institutions and SWOG investigators with the objective of integrating promising preclinical approaches into ongoing and future clinical trials rapidly. These awards will support projects with a CSHL or JAX scientist as co-pi in a true partnership with a SWOG investigator co-pi, with the goal of using technology platforms available at CSHL and JAX to obtain preliminary data that can then be used as the basis for grant funding and/or the development of clinical protocols. Priority will be given to pilot projects that either (1) address issues germane to ongoing or planned SWOG clinical trials; or (2) show potential for leading to a future clinical trial, especially in the area of personalized medicine. Funding up to $100,000 in direct costs will be awarded for pilot projects. Support for these awards is provided by The Hope Foundation, the ITSC U10 grant award, and funds from CSHL or JAX (depending on the home institution of the awardees). In the case where there are collaborations between an investigator and both CSHL and JAX, funding will be allocated according to percent effort of each basic science institute. The number of awards and duration of program is contingent upon available funding from The Hope Foundation, CSHL, and JAX. The available level of funding should support up to four pilot projects in the next year. OBJECTIVES The ITSC Program is intended to foster novel scientific ideas, agents, targets, and technologies that have the potential to substantially advance the practice of clinical cancer research within SWOG and the NCTN. For example, a project may seek to identify new bio-markers for detection or evaluation of drug

2 efficacy, develop new technologies for monitoring therapeutic response, identify resistance mechanisms, carry out co-clinical trials in animal models, exploit genomic data for computational prediction of resistance, or evaluate therapeutic combinations in silico or in animal models to optimize initial potency and avoid resistance. Technology platforms developed and refined at CSHL and JAX provide a broad menu of approaches that, combined, describe an ITSC Discovery Engine able to support collaborative translational research. SWOG investigators bring pressing problems in the treatment of cancer to the ITSC. Research partners at CSHL and JAX engage with them to advance discoveries toward application to impactful clinical trials. Elements of the Discovery Engine include: PDX models and genetically engineered mouse models form a platform for repeated interrogation of individual patient cancers, enabling studies of primary and acquired therapy resistance. Preclinical experimental therapeutics for evaluation of drug efficacy, pharmacology and toxicity in cancer animal models (pancreatic, breast, lung, etc.). Humanized PDX models bearing sustained engraftment of functional human immune components and human tumors for developing and testing immunotherapeutics. Sensitive animal imaging modalities (fluorescence, bioluminescence, ultrasound, PET and CT) for non-invasive imaging of tumor growth and treatment responses in animal models. Organoid cultures or progenitor cell clones derived from primary patient samples support studies of response to therapy, clonal evolution, tumor heterogeneity and development of resistance. Efficient genome editing or gene regulatory technologies enable rapid new GEM model production including humanizing alleles to optimize PDX hosts, as well as in vitro manipulation of oncogenic and therapy resistance pathways. Diversity outbred (DO) stock for high resolution mapping of germline susceptibility and resistance alleles to therapy associated toxicities and environmental carcinogens. High throughput genome scale analyses to determine structural aberrations and mutations, alterations in nuclear architecture and long-range interactions that govern cell-type specific, coordinated gene expression Single cell DNA and RNA analytics for interrogation of specific cell population properties, tumor heterogeneity, circulating tumor cells, and mutational frequency CLIA, CAP certified panel of coding exons of over 350 cancer-related genes detecting SNVs, indels and CNVs. Computational/bioinformatic pipelines for analysis of genomic data The application must provide a well-defined plan for achieving the goals of the pilot. In addition, each proposal must clearly describe the overarching clinical need or application that the pilot will address. KEY DATES Letter of Intent Due Date: July 31, 2018 Notification if full application is requested: August 17, 2018 Full application Due Date: October 1, 2018 Award Announcement: November 1, 2018 Award start: January 31, 2019 ELIGIBLE APPLICANTS Any CSHL, JAX and SWOG investigator is encouraged to propose pilot studies for this program.

3 All studies will be a joint program between a co-pi from CSHL or JAX, partnering with a SWOG-based clinician Co-PI. The CSHL or JAX co-pi will serve as the contact for the project. Each site (JAX, CSHL, SWOG) may send multiple proposals for the annual RFAs. Individual applicants may submit more than one application, provided that each application is scientifically distinct. Awardees will be expected to present their work at one or more semiannual SWOG group meetings and to adhere to Group policies and procedures as applicable to the project. Though funding is awarded for Investigator-initiated projects, funding will be awarded directly to an institution. APPLICATION REQUIREMENTS A letter of intent is due July 31, The ITSC Executive Committee will select the projects for which a full application is requested, with input from SWOG Disease Committee Chairs when applicable. Projects will be prioritized based on (1) scientific merit; and (2) clinical relevance and potential to integrate with clinical trials. Priority will be given to pilot projects that address issues germane to ongoing or planned SWOG clinical trials, or to projects that show potential for leading to a future clinical trial. In addition, if tissues are required for the pilot, it must be clear that the tissues are available. The LOI should be no more than two pages, follow the format specifications below, and include: Name, institution and of JAX/CSHL investigator(s) Name, institution and of SWOG clinical investigator(s) Clearly state the hypothesis to be tested (one sentence) Describe the overall goals and approach of the progress, including specific aims (one paragraph) Describe the clinical need or applications that the pilot will address (one paragraph). If relevant, list any ongoing clinical trial(s) this projects addresses Estimate of the time required to initiate the project (e.g. to obtain regulatory approvals or to get models up and running) Rough estimate of budget In addition: Provide Biosketch for co-pis (NIH format, up to five pages, include other support). If human tissue samples are required: Provide confirmation that the samples can be obtained for the project (i.e. letter from the provider, confirming samples from appropriately consented patients are available). If SWOG tissue samples are required, complete Sections I-III of the Biospecimen Request Form: Applicants will be notified by August 17, 2018 if a full application is requested. The full ITSC application for selected pilots is due October 1, 2018: 1. Cover Letter to include: project title; PIs (name, institution, department, relationship to SWOG); and a list of other key personnel & their role on the project. 2. PHS398 Mandatory Forms ( a. Face Page b. Budget for Entire Proposed Period. The total direct cost budget for each participating institution should be clear. c. Budget Justification (1 page). d. Biographical Sketch for Principal Investigators (up to 5 pages, using new NIH format)

4 e. Other Support 3. Research Plan, to include: a. Summary/abstract (brief background and underlying hypothesis) and specific aims (1 page) b. Research proposal (3 pages, inclusive of tables, graphs) c. Clinical Relevance (1 page) d. References FORMAT SPECIFICATIONS Font: Use an Arial, Helvetica, Palatino Linotype or Georgia typeface, a black font color, and a font size no smaller than 11 points. A symbol font may be used to insert Greek letters or special characters. A smaller font size may be used for figures, graphs, diagrams, charts, tables, figure legends, and footnotes, but this type must follow the font typeface requirement and be readily legible. Type density, including characters and spaces, must be no more than 15 characters per inch. Type may be no more than six lines per inch. Print must be clear and legible. Paper Size and Page Margins: Use standard paper size (8 ½" x 11") Use at least one-half inch margins (top, bottom, left, and right) for all pages. SUBMISSION Letters of intent and full applications should be sent as a single searchable PDF file with the subject line SWOG/ITSC Pilot Project - [PI last name]. Letters of Intent should be sent to Denise Roberts at robertsd@cshl.edu. Full applications should be sent to the following, depending on the home institution of the JAX or CSHL PI: JAX: grants@jax.org CSHL: itsc@cshl.edu BUDGET LIMITATIONS Pilots will be funded at the level of up to $100,000 (direct costs) for one year. PI salaries should be calculated using the NIH salary cap. A maximum of 5% effort each for the CSHL/JAX co-pi and the clinical co-pi may be requested. Funds in this award may be used to conduct assays studies/analyses associated with clinical trials and/or to conduct pilot clinical studies for biospecimen acquisition to obtain preliminary data. Funds may not be used to support a therapeutic intervention trial requiring patient enrollment. SCORING CRITERIA Awards will be issued through a competitive, peer-review process that includes representatives from SWOG, Cold Spring Harbor Laboratory, and The Jackson Laboratory, as well as additional external reviewers, as deemed necessary.

5 All applicants will receive an Overall Impact Score and brief written critique. The scoring criteria and definitions of the Translational Research Award coincide with the current NIH peer review process, with range of scores from 1 (best) to 9 (worst). The 5 core NIH criteria will be used, with additional criteria gauging feasibility and pertinence to the goals of the ITSC. Overall Impact. Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five core review criteria, and additional review criteria (as applicable for the project proposed). Core Review Criteria. Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit, and give a separate score for each. A score will also be provided for feasibility. - Significance. Does the project address a clinically important problem or a critical barrier to progress in the field? If the aims of the project are achieved, is there the potential for a significant clinical impact or improvement in clinical practice? Will successful completion of the aims change the concepts, methods, technologies, treatments, services or preventative interventions that drive this field? - Investigator(s). Are the PD/PIs, collaborators, and other researchers well suited to the project? Do the investigators have complementary and integrated expertise with sufficient experience to move discoveries to clinical application in SWOG trials? - Innovation. Does the proposal have the potential to advance the field? Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement or new theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? - Approach. Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? - Feasibility and pertinence. Is the project feasible and can it be concluded within the projected timeframe? Is there a clear potential for this project to integrate with late-phase clinical trials? Does the project demonstrate a synergistic relationship between scientists at CSHL or JAX and clinicians in SWOG or other NCTN partners? PAYMENT: Payment will be remitted as described in the executed Award Notice from the SWOG ITSC. Certain contingencies for release of funds may exist, including provision of Just-In-Time data, confirmation of SWOG samples/bank inventory, IRB approval, or updated Other Support forms, as applicable. Since the funding for pilots comes from several different sources, the funds will be administered differently based on restrictions in distribution. For funds from The Hope Foundation portion of the award, indirect costs are limited to a rate of 25%. Funds provided by The Jackson Laboratory must be

6 used within The Jackson Laboratory, and funds provided by Cold Spring Harbor Laboratory must be used within Cold Spring Harbor Laboratory. PROGRESS REPORTS: Awardees will be required to provide a 2-page progress and financial report nine months after the initiation of funding. They will be expected to present their results, when requested, either at one of the semiannual SWOG meetings or at one of the Translational Workshops held at CSHL or JAX. Please note: In compliance with the Physician Payments Sunshine Act, components of this program (travel, meals, educational materials) may require reports of payment or transfer of value provided to all US licensed physicians. The Hope Foundation will alert grantees should regulations mandate reporting. INQUIRIES: All inquiries related to this may be directed to: Barbara Tennent (JAX), Barbara.tennent@jax.org, (207) Denise Roberts (CSHL), robertsd@cshl.edu, (516)