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

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

  • Please contact your local Research Scientific Director (RSD, US only) or country specific liaison for guidance that may pertain to your specific proposal prior to its submission, to ensure that your concept falls within the scope and interest of the IISP Program.
  • Carefully review the AOIs below. Concepts that are not designed to encompass the AOIs may be rejected without further review. Occasionally, we receive concepts 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 concept, please review with your RSD or appropriate liaison.
  • The Pembrolizumab Investigator Initiated Studies Program is large with numerous approved studies, which include single agent, standard of care combinations and radiation combinations. Please check http://www.clinicaltrials.gov to ensure similar studies are not ongoing, as well as your RSD or country specific liaison for what may be possibly in development.
  • Highly competitive studies include documentation of successful and timely accrual and publication of studies in similar indications. Failure to provide such information may be sufficient for rejecting a concept.
  • 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. Concepts lacking such documentation may be rejected.
  • The program encourages young investigators to be involved in conducting IISP studies under the guidance of a mentor. In such cases, please specifically mention in the concept form the intent of a mentored IISP. Include CVs of both investigator and mentor, as well as a detailed letter from the mentor describing the mentoring plan and how this IISP will help the investigator meet their career objectives.
  • The Pembrolizumab IISP program does not include any MSD investigational pipeline agent at this time for independent clinical investigations and will not be considered. Should you have interest in pipeline agents for preclinical or early clinical evaluations, please contact your RSD/liaison for discussion with the appropriate MSD team member.

 

The Areas of Interest for Pembrolizumab are as follows:

Bladder Cancer

Signal finding areas of interest or interesting questions the medical community would like answered:

  • Pembrolizumab combinations in perioperative setting for MIBC or NMIBC (i.e. olaparib, chemotherapy, targeted therapy, novel agents, etc.)
  • Novel strategies for bladder preservation
  • Combinations with pembrolizumab in I/O refractory population
  • Pembrolizumab in combination with radiation therapy for advanced/metastatic disease

  Breast Cancer

  • Pembrolizumab combinations in patients with prior PD-1/IO therapy
  • Window of opportunity studies; sequencing, novel combinations, breast cancer subtypes
  • Biomarker studies: Activity in subgroups and potential for predictive biomarkers
  • Patient populations of interest for pembrolizumab combination therapy: TNBC early recurrence (0-6 months), leptomeningeal disease, low ER/PR, and geriatric population
  • Pembrolizumab combinations with lenvatinib

 Colorectal Cancer

  • Pembrolizumab combinations for metastatic MSI-H or MSS CRC with strong scientific/pre-clinical rationale, including but not limited to combination partners with immune or metabolic targets
  • Adjuvant approaches incorporating pembrolizumab combinations for Stage 3, high-risk MSS CRC
  • Neo-adjuvant approaches with obligatory tumor biopsies in order to enhance our understanding of biology

GI/ Gastric

Gastric/Esophageal Cancers

  • Pembrolizumab combination therapy, including novel agents, with strong biological and clinical rationale that potentially address resistance pathways and have established safety (excluding chemo-radiation approaches)
  • Exploration of drug sequencing
  • Incorporation of novel biomarker strategies. Highest interest in PDL1-negative and MSS tumors
  • Pembrolizumab in combination with olaparib or lenvatinib for esophageal cancers

Pancreatic Cancer

  • Pembrolizumab combination, including standard of care, chemotherapy, or novel agents, with strong biological and clinical rationale and have established safety. Incorporation of novel biomarker strategies are desirable.
  • Pembrolizumab in combination with olaparib or lenvatinib

Anal Cancer

  • Pembrolizumab combination with novel agents, with strong biological and clinical rationale and have established safety

Gynaecological Cancers

Ovarian cancer

  • Chemotherapy combinations but not in front-line
  • Platinum sensitive disease
  • Novel combinations post IO/post PARPi
  • Rare histologies

Cervical cancer

  • Novel pembrolizumab combinations
  • Chemo-radiation combination with intensive correlative studies
  • Post PD1
  • Rare histologies

Endometrial cancer

  • Novel pembrolizumab combinations
  • Window of opportunity study of pembrolizumab in early stage, high grade disease
  • MSI-High: pembrolizumab combinations and post IO in MSI-H
  • Rare histologies

Vulvar cancer

  • Single agent or combinations. Special interest in methods to evaluate clinical efficacy in patients with non-measurable disease

Haematological Malignancies

Classical Hodgkin’s Lymphoma

  • Front line studies in the advanced and adult population in high risk groups (PET 2 still 4-5, bulky mediastinal disease and others)
  • Front line studies in early adult population to avoid radiotherapy in high risk cases
  • Front line combination in elderly patients

T cell and NKT cell lymphoma

  • Pembrolizumab combinations in first line and relapsed setting

Diffuse large B cell lymphoma

  • Novel combinations with chemotherapy or non-chemotherapy agents in 1st line of R/R setting. 

Multiple Myeloma

  • Novel combinations (Non-IMID in the relapsed/refractory setting, non-carflizomib)

Myeloid Diseases

  • Novel combinations (FLT-3 inhibitors and IDH)

Head & Neck Cancers

  • Novel combinations in salivary gland and thyroid carcinomas
  • Nasopharyngeal carcinoma (NPC): combinations with pembrolizumab
  • Post progression in DTC with pembrolizumab in combination/sequence with lenvatinib
  • Pembrolizumab +/- other agents in long term stable immunocompromised cSCC (CLL/controlled HIV)
  • Alternative regimens for R/M HNSCC including post IO progression– Novel / Chemo
  • R/M HNSCC pembrolizumab combinations in patients w biomarker sub-population (include TMB)
  • Intra-tumoural strategies in locoregional recurrence (Pipeline off limits)

Hepatobiliary Cancers

  • Pembrolizumab combinations in HCC which may help re-sensitize after pembrolizumab PD
  • Pembrolizumab and radiomic predictors of response
  • Pembrolizumab and the microbiome
  • Pembrolizumab combinations in 2L biliary (IDH, HER-2 etc.)

Thoracic Malignancies

NSCLC

  • Novel neoadjuvant combos
  • Novel combinations in IO refractory resistant patients
    • Treatment paradigm pattern of progressions
  • Novel combinations in mutation driven patients
    • VEGFRi and EGFRmut
    • Non-EGFRmut tumors
  • Chemo combinations in special populations (PS2 patients, elderly)
  • Novel biomarker selected populations – neoadjuvant combo

SCLC

  • Novel combinations in I/O refractory resistant patients

Mesothelioma

  • Combo with TKI and/or I/O refractory resistant 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 resistant/refractory patients
    • Mucosal melanoma
    • Uveal melanoma
    • Brain metastases
  • Neoadjuvant therapy
  • Real world data on treatment patterns and outcomes in patients excluded from clinical trials
  • Combinatorial approaches for advanced Merkel cell carcinoma

 Innovative Strategies

  • Pembrolizumab-based combinations in advanced cancers with a high unmet medical need. Lenvatinib + pembro combos are encouraged; proposals with a translational rationale/evidence or component (e.g. neoadjuvant) are highly encouraged.

Pediatric Malignancies

  • Hodgkin lymphoma
  • MSI-H/dMMR
  • Adolescent melanoma

Prostate Cancer

  • Neo-adjuvant or adjuvant studies of pembrolizumab as monotherapy and in combination
    • Combinations of interest include, but not limited to TGFß antagonists, CDK-12 mutation, targeted radiation assets (e.g. PSMA-Actinium, and Thorium), olaparib, novel immune checkpoint agents, VISTA, and nano-particle delivery therapeutics
  • Primary disease, high risk after primary definitive therapy and locally advanced/metastatic disease
    • Combinations with oncolytic viral assets, radiation, PARP inhibition, CDK-12 mutation positive patient population etc.
    • Novel combinations of pembrolizumab for Small cell / neuroendocrine-like differentiated disease
  • Studies evaluating Immune infiltration in early and advanced prostate cancer; mutational load, transcription into neoantigenicity, negative inflammatory infiltration

Renal Cell Carcinoma

  • Novel combination approaches
    • Combinations of interest include, but not limited to metabolic pathways (adenosine), epigenetic pathways (EZH2), targeting of the myeloid compartment and other emerging immune and non-immune pathways
    • This includes naïve patients and patients who received prior checkpoint therapy
  • Pembrolizumab combination approaches in patients undergoing nephrectomy or metastasis resection
  • Studies evaluating Immune infiltration, transcription into neoantigenicity, negative inflammatory infiltration in subjects with advanced RCC including who have received prior systemic treatment

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 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
  • Pathways
    • Angiogenesis, hypoxia, Epithelial-mesenchymal transition (EMT)

Pembrolizumab combinations

  • Identify mechanisms of action associated with reported clinical response to anti-PD-1 combination treatment (Reverse translational studies):
    • Pembrolizumab combinations with innate immune mechanisms that might turn “cold” tumors “hot”
    • Pembrolizumab combinations to enhance tumor antigen responses and decrease tolerance
  • Targeting the tumor-stromal-immune cell axis:
    • Identify mechanisms of action that modulate the tumor stroma and vasculature to enhance immune cell trafficking
    • 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, Tumor-associated macrophages (TAMs), Myeloid derived suppressor cells (MDSCs)

 

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, 2018 January 2019 February 2019
March 31, 2019 April 2019 May 2019
June 30, 2019 July 2019 August 2019
September 30, 2019 October 2019 November 2019
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.