Below you will find our updated Areas of Interest (AOI) for the upcoming Pembrolizumab Oncology Translational Studies Program (OTSP) 2021 submission cycle. Please be aware that this is a highly competitive process.To help to prepare a successful, 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. Proposals that are not designed to encompass at least one AOI may be rejected without further review. Occasionally, we receive proposals not included in the AOIs that represent innovative biology and are ultimately of great interest. If you believe this may apply to your proposal, 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 proposal 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 (for example, prior study recruitment numbers, trials participated in, rates of accrual, etc.) 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 proposal.
- 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. Proposals 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 proposal 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 proposals requesting their use will not be considered.
- The program requests that investigators specify how they will support diversity in enrollment to include traditionally underrepresented minorities/ethnic groups.
Beginning November 1, 2020, the Oncology Translational Studies Program (OTSP) Committee will accept concept summary applications prior to proposals within our current AOIs. For this review cycle, we require that all applicants complete and submit the concept summary form by January 22, 2021. 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 concept summary form to your local RMSD via e-mail by end of business January 22, 2021. Please note that late submissions will not be reviewed.
Pages 1-5 are required for all submissions. 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 5th, 2020:
- Accepted - please submit a proposal for consideration to Visiontracker by end of business east coast time March 5th, 2021.
- Declined - please do not submit a proposal for review.
Please note that acceptance of your concept summary proposal for a proposal submission is not a guarantee of final approval. It simply indicates that the OTSP Committee will review a proposal for consideration of support. If your concept summary is accepted, you will need to complete the proposal template and submit toVisiontracker for consideration during the 2020 review cycle. The OTSP proposal 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 2021. Decisions will be made on the basis of scientific merit, innovation, and strategic fit within the AOI. Please review the areas of interest carefully and abide by the timelines as outlined below.
- 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
2021 Areas of Interest for Oncology Translational Studies Program
2021 High Level Areas of Interest
At a high level, all proposals submitted should address one of the following high-level mechanisms:
- Mechanisms of acquired resistance
- Mechanisms of primary resistance
- Mechanism of response
- Understanding mechanisms of response vs 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
At a more refined level, the OTSP Committee is interested in proposals studying immune cells and/or biology in relation to one (or more) high level areas of interest:
2021 Biology Component:
Immune Biology: Analysis of immune cell biology in the context of response or resistance to pembrolizumab monotherapy or combination therapy:
- Analysis of stromal biology in response or resistance to pembrolizumab and/or combination therapy
- Identification and immune activity of myeloid cell lineages
- Mechanisms of T cell trafficking and T cell exclusion from tumors
- Mechanisms of tumor and immune system interactions
- On-treatment dynamics and biology of T cell subpopulations focusing on mechanisms of polarization, exhaustion, and senescence
- Role and identification of CD4+ cell populations associated with pembrolizumab response
- Defining immune biology between low and high tumor mutation burden tumors
- Intra-tumor and inter-lesion heterogeneity
2021 Immune Cell Component
- Investigation and characterization of immunologically defined T and NK cells in the context of an anti-tumor response or resistance to pembrolizumab including:
- Immunologically defined cell populations involved in innate or adaptive immunity
- Conventional or unconventional T cell populations
- Investigation and characterization of the following immunologically defined non-T cell immune cell subsets in the context of an anti-tumor response or resistance to pembrolizumab:
- Identification and characterization of myeloid lineage populations
- Identification and characterization of B cell lineage populations
- Identification and characterization of immunosuppressive neutrophil lineage population
Circulating tumor DNA (ctDNA) Areas of Interest Study Guidelines:
- ctDNA studies of potential interest:
- Studies where retrospective ctDNA analysis is used to investigate pembrolizumab response or resistance in line with the overall AOIs
- Studies looking at retrospective analysis of ctDNA for monitoring of minimal residual disease burden or assessment of on-treatment responses or progression
- 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
AOI Additional Guidance:
- 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 the following technologies to generate datasets in alignment with project hypotheses are encouraged:
- Single cell RNAseq or high dimensional flow cytometry for identifying immune cell populations or elements of tumor biology
- Spatial transcriptomics
- Functional immune cell assays including organoid cultures
- Patient selection using experimental biomarker assays or technology 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 of pathology samples for patient selection or as a biomarker of response
- 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.
- Concept Summary Submissions accepted from November 1, 2020 – January 22, 2021.
- Communication to investigator of Concept Summary decision: February 5, 2021
- Deadline for Proposal submission to Visiontracker with estimated budget: March 5, 2021
- Communication to investigator of selected Proposals: Late May 2021
||2021 Review Cycle
|Concept Summary submission to RMSD or country specific liaison
||January 22, 2021
|Concept Summary decisions communicated to investigators
||February 5, 2021
|Proposal submission uploaded toVisiontracker
||March 5, 2021
|Proposal submission decisions communicated to investigators
||Late May 2021