Investigator Studies Program (MISP): Oncology Translational Studies Program (OTSP)
Below you will find our updated Areas of Interest (AOI) for the upcoming Pembrolizumab Oncology Translational Studies Program (OTSP) 2022 submission cycle. Please be aware that this is a highly competitive process.To help to prepare a successful submission, we are providing the following guidance:

  • Please contact your local Research Medical Scientific Director (RMSD, US only) or country-specific Global Medical Affairs Field Medical liaison for guidance that may pertain to your specific proposal prior to its submission, to ensure that your proposal falls within the scope and interest of the Oncology Translational Studies Program and AOIs.
  • Carefully review the AOIs below. Concepts that are not designed to encompass at least one AOI may be rejected without further review. Occasionally, we receive Concepts not included in the AOIs that represent innovative biology and are ultimately of great interest. If you believe this may apply to your Concept , please review with your RMSD or appropriate country-specific liaison for additional programmatic assessment by the appropriate MSD team and by the OTSP review committee.
  • The Pembrolizumab Investigator-Initiated Studies Program (IISP) is large with numerous approved studies, which includes single agent, standard of care systemic therapies, combinations with novel compounds in development, and/or radiation combinations. Please check www.clinicaltrials.gov to ensure similar studies to your proposed concept are not already approved or ongoing. You may also discuss what may be possibly in development with your RMSD or country specific liaison.
  • Please include documentary evidence of successful and timely accrual and publication of investigators’ studies in similar indications where possible. Operational deliverability is carefully considered in our assessment process.
  • Highly competitive studies include documentation of successful and timely accrual and publication of studies in similar indications. Failure to provide such information may be enough to reject a concept.
  • Combinations with non-MSD agents may be of interest. Please confirm with your country-specific liaison if the combination agent is of programmatic interest. These requests will also be reviewed by the OTSP review committee. In such cases, it is the responsibility of the investigator to procure approval for supply of third-party agents, and matching funding, where possible, which should be demonstrated with a formal letter of support. Concepts lacking such documentation may be rejected. If the agents are approved by health authorities or considered standard of care by country-specific guidelines and the agent is obtained through routine care, then no letter is required.
  • The program encourages young investigators to be involved in conducting studies under the guidance of a mentor. In such cases, please specifically mention in the concept form the intent of a mentored study. Include CVs of both investigator and mentor, as well as a detailed letter from the mentor describing the mentoring plan and how this study will help the investigator meet his/her career objectives.
  • Please note that no MSD investigational pipeline agents are presently available for use in the IIS program and concept requesting their use will not be considered.
  • The program requests that investigators specify how they will ensure diversity in enrollment to include traditionally underrepresented minorities/ethnic groups.

Beginning November 15, 2021, the Oncology Translational Studies Program (OTSP) Committee will accept concept applications prior to proposals within our current AOIs. For this review cycle, we require that all applicants complete and submit a pre-review form by January 21, 2022. For investigators outside of the US, please contact your MSD country representative for requirements and timelines.

Concept Summary Form Template

For investigators in the United States please submit a completed concept summary form to your local RMSD via e-mail by end of business January 21, 2022. Please note that late submissions will not be reviewed. Please note that character limits have been built into the forms and these cannot be exceeded. All concept summary forms will be reviewed by the OTSP Review Committee and one of two decisions will be communicated to you via e-mail by February 4th, 2022:

  • Accepted - please submit a FULL proposal for consideration to Visiontracker by end of business east coast time March 4th, 2022.
  • Declined - please do not submit a FULL proposalfor review.

Please note that acceptance of your project for a FULL proposal is not a guarantee of final approval. It simply indicates that the OTSP Committee will review a FULL proposal for consideration of support. If your concept summary is accepted, you will need to complete the FULL proposal template and submit to Visiontracker for consideration during the 2022 review cycle. The FULL proposal OTSP template will be provided by either your RMSD or country contact. Please work with your country-specific liaison if you have programmatic questions or questions surrounding the submission process.

This is a competitive grant review process that will be conducted by the Oncology OTSP committee for support in 2022. Decisions will be made based on scientific merit, innovation, and strategic fit within the AOI. Please review the areas of interest carefully and abide by the timelines as outlined below.

OTSP:

Projects must:

  • Seek to understand factors responsible for responsiveness and resistance to immunotherapy
  • Involve use of pembrolizumab-treated patient samples
  • Have primary translational, or co-primary translational/clinical, endpoints
  • Be innovative, focused, and hypothesis driven
  • Have mature hypotheses supported by existing data (e.g. preclinical, epidemiologic, etc)
  • Be adequately powered for evaluation of the primary hypothesis

2022 Areas of Interest for Oncology Translational Studies Program

2022 Areas of Interest

At a high level(category 1), proposals should seek to improve our understanding of response to pembrolizumab-based immunotherapy and should be focused on one or more of the following:

  • Mechanisms of resistance
  • Mechanism of response
  • Understanding mechanisms of response or resistance in low tumor mutation burden tumors
  • Mechanisms for overcoming resistance to pembrolizumab or enhancing pembrolizumab activity through combinations with olaparib, lenvatinib, standard of care agents, or agents in development with an established recommended Phase 2 dose

2022 Immune Cell Component (category 2)

At a more refined level, the OTSP Committee is interested in proposals studying immune cells and/or biology in relation to one (or more) prioritized high level areas of interest:

  • Investigation and deep level characterization of defined myeloid lineage populations in the context of an anti-tumor response or resistance to pembrolizumab
  • Conventional and unconventional T-cell populations, including NK cells

2022 Circulating tumor (ctDNA)Study Guidelines:(category 2)

ctDNA-related areas of potential interest:

  • Retrospective analyses of ctDNA as a surrogate for monitoring of minimal residual disease burden for assessment of on-treatment responses or disease progression
  • Retrospective analyses of ctDNA as a predictor of response or progression
  • ctDNA as a tool to investigate tumor biology or genetics
  • Note:
    • Studies using ctDNA assays for prospective clinical trial enrolment will require additional discussion
    • Studies where ctDNA assays are intended for use for on-treatment patient clinical decision making are discouraged
    • Studies using locally developed ctDNA assays within an academic or hospital setting will require additional discussion

2022 Immune Biology Components:(category 2)

Analyses of immune cell biology in the context of response or resistance to pembrolizumab monotherapy or combination therapy, primarily focused on the following topics, are of potential interest:

  • Analysis of stromal biology in response or resistance to pembrolizumab and/or combination therapy
  • Identification and immune activity of myeloid cell lineages
  • Mechanisms of immune cell trafficking and exclusion from tumor
  • Mechanisms and identification of tumor cell and immune cell interactions
  • On-treatment dynamics and biology of CD4+ T cell subpopulations focusing on mechanisms of lineage polarization and exhaustion

General Considerations:

Proposals in all cancer indications are welcome.

  • Submissions employing longitudinal patient sampling, including trials conducted in the neoadjuvant setting, are strongly encouraged.
  • Submissions that utilize multidimensional approaches are of interest:
  • Patient selection using experimental biomarker assays or technology that are not regulatory-approved will require additional discussion
  • Submissions focused on the following areas are discouraged:
    • 16sRNA or metagenomics analysis of microbiome populations
    • Purely in vitro cell line or in vivo animal models
    • Clinical trials using experimental assays for on-treatment clinical decision making
    • Radiomics imaging analysis
    • Artificial intelligence-based analyses:
      • H&E stained FFPE tissue sections
      • Combined integrated translational and clinical datasets
    • Biomarker identification or validation

Expectations of the OTSP are as follows:

Clinical and translational data sharing is an intrinsic requirement for studies funded under the OTSP program. Expectations regarding types of MSD requests for data will be provided.

Data Tiers

Critical Timelines:
  • Concept Summary Submissions accepted from November 1, 2021 – January 22, 2022.
  • Communication to investigator of Concept Summary decision: February 4, 2022
  • Deadline for FULL Proposal submission to Visiontracker with estimated budget: March 4, 2022
  • Communication to investigator of selected FULL Proposals: Late May 2022

Deadline Dates/Activity 2021 Review Cycle
Concept Summary submission to RMSD or country specific liaison January 21, 2022
Concept Summary decisions communicated to investigators February 4, 2022
FULL Proposal submission uploaded toVisiontracker March 4, 2022
FULL Proposal submission decisions communicated to investigators Late May 2022


MISP Information
This site is intended for US investigators only. Investigators outside of the US interested in submitting research proposals to the Investigator Studies Program should contact their local MSD office.