Oncology Investigator Initiated Studies Program (IISP)
To advance science and improve patient care by supporting, through the provision of drug/vaccine and/or total/partial funding, high-quality research that is initiated, designed, implemented and sponsored by external investigators. Results will be generated and properly disseminated in peer-reviewed publications.
Pembrolizumab Quarterly Drug Only Review Cycle

Dear prospective investigators,

We are currently accepting proposals requesting “drug only” support for the Pembrolizumab Investigator Initiated Studies Program (IISP). Please be aware that this is a highly competitive process. “Drug only” proposals are reviewed with the same scientific rigor as those requesting funding.

To help to prepare a successful proposal, we are providing the following guidance:

  • Please contact your local Research Medical Scientific Director (RMSD, US only) or country specific liaison for any guidance pertaining to your specific concept prior to its submission, to ensure that it falls within the scope and interest of the Investigator Initiated Studies Program (IISP).
  • Carefully review the Areas of Interest (AOI) below. proposals that are not within the scope of these AOIs may be rejected without further review. Occasionally, we receive proposals out of the AOIs that represent "out of the box" thinking and are ultimately of great interest. If you believe this may apply for your proposal, please review with your RMSD or appropriate liaison prior to submission.
  • The pembrolizumab Investigator Initiated Studies Program (IISP) is large with numerous approved studies, which include single agent, standard of care systemic therapies, and/or radiation combinations. Please check www.clinicaltrials.gov to ensure similar studies to your proposed 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 of successful and timely accrual and publication of investigators’ studies in similar indications where possible. Operational deliverability is carefully considered in our assessment process.
  • Combinations with non-MSD agents may be of interest. In such cases, it is the responsibility of the investigator to procure approval for supply of third-party agents, which should be demonstrated with a letter of support. proposals lacking such documentation may be rejected.
  • The program encourages young investigators to seek guidance from a mentor in submitting IISP proposals. If working with a mentor please also provide their CV where possible, along with a detailed letter from the mentor describing the mentoring plan and how this IISP will help the investigator meet their 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.
  • In addition, please note that proposals with safety as a sole primary endpoint will not be considered.
  • proposals for which the primary purpose is translational studies should be directed to our Oncology Translational Studies Program.
  • The program requests that investigators specify how they will support diversity in enrollment to include traditionally underrepresented minorities/ethnic groups.
  • Please complete the proposal template and submit to Visiontracker with your updated CV by the deadlines below for consideration.

The Proposal Template for clinical studies can be found here.

The Areas of Interest for Pembrolizumab are as follows:

Bladder Cancer

Early Stage:

  • Pembrolizumab combinations, including standard of care, chemotherapy, or novel agents, with strong biological and clinical rationale and have established safety:
    • for the treatment of both intermediate risk and high risk NMIBC including patients with varying prior exposure to BCG;
    • for BCG-intolerant patients or patients unable to receive BCG
    • bladder preservation strategies in MIBC
    • that potentially address pembrolizumab response or resistance pathways;
    • includes upper tract tumors;
  • Incorporation of novel biomarker or translational strategies*

Late Stage:

  • Pembrolizumab combinations that potentially address resistance pathways.
  • Incorporation of novel biomarker or translational strategies*
  • Maintenance strategies

Breast Cancer

  • Use of pembrolizumab after progression on prior PD-1/L1 inhibitor or other I/O.
  • Novel pembrolizumab combinations, such as with other I/Os, ADCs, TKIs, etc. (excluding adjuvant).
  • Studies in clinically relevant biomarker subsets.

Colorectal Cancer

  • Metastatic MSI-H or MSS colorectal cancers: pembrolizumab novel combinations (excluding chemo-only combinations, RT only combinations, or VEGF only combinations) with strong scientific/pre-clinical rationale, including groups with previous I/O exposure.
  • Locally advanced or metastatic rectal cancers: studies of pembrolizumab single agent or with novel combinations, including biomarker-defined groups.
  • Locally advanced or metastatic anal cancers: studies of pembrolizumab single agent or with novel combinations, in clinically relevant biomarker subsets, including but not limited to HPV.

GI/ Gastric

Esophageal and gastric Cancer (Highest interest in MSS tumors)

  • Pembrolizumab combination therapy, including novel agents, with strong biological and clinical rationale that potentially address resistance pathways:
    • In a neo-adjuvant/ adjuvant setting
    • Metastatic/ locally advanced disease
    • Previous IO exposure
    • HER2+ disease setting
  • Incorporation of novel biomarker or translational strategies*
  • Exploration and optimization of drug sequencing with pembrolizumab
  • Innovative trial designs, consider risk stratification for relapse in the adjuvant setting where appropriate, utilizing novel biomarkers or assays

Pancreatic Cancer

  • Pembrolizumab combinations with chemotherapy or novel agents, with strong biological rationale and pre-clinical evidence of activity in murine models. Evidence of acceptable safety profile for these combinations is recommended.
  • Innovative trial design for earlier stages of disease is of interest, including novel surrogate endpoints of efficacy, and novel assay development (ctDNA, liquid biopsy, etc.)
  • Incorporation of novel biomarker or translational strategies, especially in metastatic disease*.

Gynaecological Cancers

Ovarian cancer

  • Combination therapies in recurrent ovarian cancer including novel investigational agents
  • Particular interest in post IO / post PARPi
  • Rare histologies
  • Incorporation of novel biomarker or translational strategies including for monitoring response to treatment*

Cervical cancer

  • Combination therapies in recurrent cervical cancer including novel investigational agents
  • Rare histologies
  • Pembrolizumab combinations including IO naive and IO refractory
  • Incorporation of novel biomarker or translational strategies including for monitoring response to treatment*

Endometrial cancer

  • Combination therapies in recurrent endometrial cancer including novel investigational agents
  • Rare histologies
  • Pembrolizumab combinations including IO naive and IO refractory
  • Incorporation of novel biomarker or translational strategies including for monitoring response to treatment*

Vulvar cancer

  • Combination therapies including novel investigational agents

Hematological Malignancies

Classical Hodgkin’s Lymphoma

  • Pembrolizumab monotherapy/combinations as maintenance (consolidative therapy) post Autologous Stem Cell Transplant.
  • Pembrolizumab as monotherapy or in combination in relapsed patients.
  • Pembrolizumab in combination in PD-1 refractory patients.

Non-Hodgkin’s Lymphoma

  • Novel pembrolizumab containing combinations with non-chemotherapy agents in frontline and relapsed/ refractory settings in Diffuse Large B-Cell Lymphoma, Primary Mediastinal B-Cell Lymphoma, and Follicular Lymphoma.
  • Pembrolizumab in combination with cell therapy

Multiple Myeloma

  • Novel pembrolizumab containing (no IMiD or carfilzomib) combinations with focus on bispecific Antibodies, Antibody-Drug Conjugates or new mechanisms of action in the relapsed/refractory setting.

Head & Neck Cancers

Recurrent/Metastatic HNSCC

  • Novel combinations in R/M HNSCC
    • Including PDL-1 negative populations
  • Novel strategies after progression on anti-PD-1/PD-L1 (IO refractory)
  • Studies focused on underrepresented populations in clinical trials (e.g. race, ethnicity).

Locally Advanced HNSCC

  • Neo-adjuvant pembrolizumab + chemotherapy or novel combination in salvage surgery setting for recurrent HNSCC
  • De-escalation strategies in locally advanced disease
    • Including HPV+ oropharynx cancer (OPC).
  • Pembrolizumab + chemotherapy as induction therapy for LA HNSCC
  • ChemoRT followed by adjuvant pembrolizumab in LA HNSCC (combination therapies + sequencing)
  • Studies focused on underrepresented populations in clinical trials (e.g. race, ethnicity).

Nasopharyngeal Carcinoma

  • Novel combinations with pembrolizumab + chemotherapy in EBV-associated NPC.

Salivary Gland and Thyroid Carcinomas

  • Novel strategies in combination with pembrolizumab in salivary gland and thyroid carcinomas

Hepatobiliary Cancers

Hepatocellular Cancers

  • Neoadjuvant studies in early stages of HCC
  • Strategies to improve pembrolizumab efficacy in advanced HCC including:
    • Uncommon subtypes
    • I/O refractory
    • Evaluate predictors of response to I/O (blood-based markers, imaging, etc.)*
  • Child Pugh B group with pembrolizumab combinations (excluding TKI).
  • Sequencing of therapy in advanced disease

Biliary Cancers

  • Pembrolizumab combinations in preselected molecular subsets (including but not limited to IDH, FGFR, HER-2).
  • Neoadjuvant/adjuvant studies in early stages of biliary cancer
  • Strategies to improve pembrolizumab efficacy in advanced biliary cancer including
    • Uncommon subtypes
    • Evaluate predictors of response to I/O (blood-based markers, imaging, etc.)*

Thoracic Malignancies

NSCLC

  • Novel neoadjuvant combinations
  • Novel combinations in IO pre-exposed patients
    • I/O, I/O combinations, ADC combinations
    • Overcoming specific mechanism of resistance (e.g. LKB-1).
    • I/O exposed in the adjuvant and neoadjuvant setting
  • Novel combinations in mutation driven patients
    • Novel TKI +pembrolizumab for non-EGFR, non-ALK mutation driven patients including KRAS mutant and others
    • Novel combinations with targeted ADC’s (e.g. HER2, cMET) and T-cell engagers
  • Novel combinations in 1L NCSLC including chemo free combinations in different biomarker subgroups (Leverage knowledge of tumor microenvironment to inform biologically rationale combination strategies)

SCLC

  • Novel combinations in 1L
    • Determining mechanisms to improve response and outcomes in 1L based on biology of disease or with the use of novel markers such as ctDNA*
    • Determining mechanisms of resistance
    • Determining approach to treatment in setting of brain metastases
  • Novel combinations in I/O pre-exposed patients

Mesothelioma

  • Novel combination in 1L and in 2L I/O naive.
    • Determining mechanisms to improve response and outcomes
  • Novel combinations in I/O pre-exposed patients

Melanoma

  • Novel combinations for patients with high-risk melanoma, with emphasis on those with a detailed/described mechanism. Examples include, but are not limited to:
    • PD-1/CTLA-4 resistant/refractory patients
    • Mucosal/Acral melanoma
    • Uveal melanoma
    • Brain metastases
  • Neoadjuvant/adjuvant therapy
  • Real world data on treatment patterns and outcomes in patients excluded from clinical trials

Other Skin Cancers

  • Novel combinations in Merkel cell carcinoma (including neoadjuvant).
  • Advanced basal cell carcinoma
  • Innovative Strategies

    • Pembrolizumab-based combinations in rarer tumor types with a high unmet medical need (primary brain tumors, sarcomas, neuroendocrine tumors and adrenocortical carcinomas remain a key focus for the program).
    • Pembrolizumab + lenvatinib, pembrolizumab + olaparib, and innovative pembrolizumab combinations
    • Proposals with a strong translational rationale/evidence or component (e.g. neoadjuvant)

    Prostate Cancer

    • Neoadjuvant or adjuvant studies of pembrolizumab as monotherapy and in combination (combinations including, but not limited to, novel immune modulating agents, including agonists and antagonists for TGFß, olaparib and nano-particle delivery therapeutics.
    • Combinations in other lines of therapy, including but not limited to, oncolytic viral agents, radiation, PARP inhibition, and agents targeting the CDK-12 pathway.
    • Novel combinations of pembrolizumab for small cell / neuroendocrine-like differentiated disease.
    • Studies that include objectives to investigate biological mechanisms of pembrolizumab response or resistance .
    • Studies evaluating biochemical failure.

    Renal Cell Carcinoma

    • Pembrolizumab combinations with novel mechanisms of action. Combinations of interest include but not limited to metabolic pathways, epigenetic pathways, targeting of the myeloid compartment and other emerging immune and non-immune pathways
    • Pembrolizumab combination studies in patients with renal cell carcinoma regardless of histology, including patients with localized disease and advanced disease where the primary tumor is in situ.
    • Concepts in treatment naïve, as well as in patients who have received prior treatment (including IO/IO or IO/TKI combinations or sequenced treatment).
    • Studies which include objectives to investigate biological mechanisms of pembrolizumab response or resistance>

    Preclinical

    • Evaluation of PD-1 Pathway Mechanism of Action
      • Understand the mechanistic basis for response/resistance to anti-PD-1. There is particular interest in studies assessing:
        • Cell Types
          • Immune cells: B cells (investigation of the role of PD-1 signaling in the humoral response), gamma delta T cells, natural killer (NK) cells, antigen presenting cells, exhausted T cells
          • Associated cells: Fibroblast reticular cells (FRCs), cancer associated fibroblasts (CAFs)
          • Tumor cells: intrinsic mechanisms that provide sensitivity or resistance to PD-1 inhibitors
          • Cancer Stem Cells.
        • Pathways
          • Angiogenesis, hypoxia, epithelial-mesenchymal transition (EMT), antigen presentation and machinery, TGFbeta
          • Immune exhaustion vs. immune senescence as it relates to response to pembro and/or other cancer immunotherapies.
    • Pembrolizumab combinations
      • Identify mechanisms of action associated with reported clinical response to anti-PD-1 combination treatment (reverse translational studies)
      • Targeting the tumor-stromal-immune cell axis:
        • Identify mechanisms of action that modulate the tumor stroma
        • Identify mechanisms of action that modulate vasculature to enhance immune cell trafficking
        • Mechanical and biophysical aspects of the tumor micro-environment
        • Evaluate the contribution of tumor intrinsic pathways to immune escape
        • Identify mechanisms of action that modulate immune suppressive cell function natural killer (NK) cells, B cells (including tumor resident B cells), myeloid cells (MDSCs, DCs, TAMs)

    *Please note that IISP studies must have a clinical efficacy primary (or co-primary) endpoint

    The MSD IISP review is a competitive process. Decisions will be made on the basis of scientific/clinical merit and strategic fit, as well as operational deliverability.

    Please note that IISPs should not compete with or duplicate any registration trial for pembrolizumab. Additionally, since the dose and schedule for pembrolizumab has been established for multiple cancers, investigation of alternate doses and schedules is of low priority.

     

    Critical Activities and Timelines:
    Review of drug only proposals will be handled on a quarterly basis according to the below schedule.
    Submission Deadline Review Meeting Expected Decision
    December 31, 2020 January 2021 February 2021
    March 31, 2021 April 2021 May 2021
    June 30, 2021 July 2021 August 2021
    September 30, 2021 October 2021 November 2021
    December 31, 2021 January 2022 February 2022
    MISP Oncology Contact Information
    To learn more or to ask a question, please contact the appropriate MSD Business Development and Licensing contact for your region.