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 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 Medical Scientific Director (RMSD, 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 Investigator Initiated Studies Program (IISP).
  • Carefully review the Areas of Interest (AOI) 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 RMSD or appropriate liaison.
  • The Pembrolizumab Investigator Initiated Studies Program (IISP) is large with numerous approved studies, which include single agent, standard of care combinations and radiation combinations. Please check www.clinicaltrials.gov to ensure similar studies are not ongoing, as well as your RMSD 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 RMSD/liaison for discussion with the appropriate MSD team member.
  • Please complete the FULL concept template and submit to Visiontracker with your updated CV by the deadlines below for consideration.

The FULL concept summary template for clinical studies can be found here.

The Areas of Interest for Pembrolizumab are as follows:

Bladder Cancer

Early Stage:

  • Pembrolizumab in combination with novel agents/strategies (e.g. intravesical drugs/devices, other systemic agents, alternative surgical techniques/technology, etc.) for the treatment of NMIBC
  • Novel strategies for bladder preservation with pembrolizumab combinations
  • Studies that include objectives to investigate biological mechanisms of pembrolizumab response or resistance

Late Stage:

  • Pembrolizumab combinations in the perioperative setting for MIBC (i.e. olaparib, chemotherapy, targeted therapy, novel agents, etc.)
  • Studies that include objectives to investigate biological mechanisms of pembrolizumab response or resistance
  • Novel combinations in PD-1/PD-L1 refractory population

Breast Cancer

  • Use of pembrolizumab after progression on prior PD-1/L1 inhibitor or other IO
  • Novel pembrolizumab combinations, such as with other IOs, AKTi, ADCs, TKIs, etc.
  • Studies in well-established clinically relevant biomarker subsets

Colorectal Cancer

  • Pembrolizumab novel* 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

    *excluding chemo-only combinations, RT only combinations, or VEGF only combinations

GI/ Gastric

Pancreatic Cancer

  • Pembrolizumab combinations, 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 with higher interest in metastatic disease. Innovative trial design for earlier stages of disease will be considered.
  • Pembrolizumab in combination with olaparib or novel agents, with higher interest in metastatic disease.

Esophageal and gastric Cancer (Highest interest in PD-L1–negative and MSS tumors)

  • Pembrolizumab combination therapy, including novel agents, with strong biological and clinical rationale that potentially address resistance pathways and have established safety
  • Pembrolizumab in combination with olaparib or lenvatinib (excluding chemoradiation approaches)
  • Concurrent chemoradiation strategies
  • Incorporation of novel biomarker strategies for patient selection
  • Exploration of drug sequencing with pembrolizumab for resensitization

Gynaecological Cancers

Ovarian cancer

  • Combination therapies in recurrent ovarian cancer
  • Particular interest in post IO / post PARPi
  • Rare histologies

Cervical cancer

  • Combination therapies in recurrent cervical cancer
  • Post PD1
  • Rare histologies

Endometrial cancer

  • Combination therapies in recurrent endometrial cancer
  • Novel pembrolizumab combinations
  • Rare histologies

Vulvar cancer

  • Combination therapies

Hematological Malignancies

Classical Hodgkin’s Lymphoma

  • Frontline pembrolizumab as monotherapy or in combinations (sequential or concurrent) in young adults, adults and elderly with Hodgkin lymphoma
  • Pembrolizumab monotherapy/combinations as maintenance (consolidative therapy) post Autologous Stem Cell Transplant
  • Pembrolizumab in novel combinations in relapsed/ refractory setting

Non-Hodgkin’s Lymphoma

  • Novel pembrolizumab containing combinations with chemotherapy or non-chemotherapy agents (including cell-based therapies) in frontline and relapsed/ refractory settings in Diffuse Large B-Cell Lymphoma, Primary Mediastinal B-Cell Lymphoma, and Follicular Lymphoma

Multiple Myeloma

  • Novel pembrolizumab containing (no IMiD or carfilzomib) combinations with focus on bispecific Antibodies, Antibody-Drug Conjugates, or cell-based therapies in the relapsed/refractory setting

Head & Neck Cancers

HNSCC

  • Novel combinations in HNSCC
  • Novel combinations in sinonasal carcinomas, including adjuvant therapy
  • Larynx preservation studies
  • Pembrolizumab + olaparib in platinum-sensitive HNSCC
  • Pembrolizumab + chemo or novel combinations in platinum-refractory population
  • Pembrolizumab + chemo or novel combinations in PD1-refractory population

NPC

  • Pembrolizumab + chemo or novel combinations in platinum-refractory population
  • Pembrolizumab + chemo or novel combinations in PD1-refractory population
  • Combinations with pembrolizumab in curative setting, including CCRT

Salivary Gland and Thyroid Carcinomas

  • Novel combinations in salivary gland and thyroid carcinomas, including adjuvant therapy in inoperable salivary gland carcinoma

Cutaneous SCC

  • Pembrolizumab +/- other agents in long term stable immunocompromised cSCC (controlled HIV)
  • Neoadjuvant therapy in cutaneous SCC

Hepatobiliary Cancers

Hepatocellular Cancers

  • Neoadjuvant/window of opportunity studies in early stages of HCC
  • I/O-I/O combinations with pembrolizumab in advanced disease
  • Strategies to improve pembrolizumab efficacy in advanced and early stages of disease
  • Strategies to re-sensitize after PD on pembrolizumab with addition of new agents

Biliary Cancers

  • Pembrolizumab combinations in preselected molecular subsets (including but not limited to IDH, FGFR, HER-2)
  • Neoadjuvant/window of opportunity studies in early stages of biliary cancer
  • I/O-I/O combinations with pembrolizumab in advanced disease
  • Strategies to improve pembrolizumab efficacy in advanced and early stages of disease

Thoracic Malignancies

NSCLC

  • Novel neoadjuvant combinations
  • Novel combinations in IO pre-exposed patients
    • I/O, I/O combinations
    • Overcoming specific mechanism of resistance (e.g. LKB-1)
  • Novel combinations in mutation driven patients
    • VEGFRi and EGFRmut
    • Non-EGFRmut tumors
    • Novel TKI +pembro for non-EGFR, non-ALK mutation driven patients
  • Novel combinations in special populations (brain mets, PS=2, autoimmune disorders)
    • VEGFRi combination in patients with brain metastases

SCLC

  • Novel combinations in 1L
    • Determining mechanisms to improve response and outcomes in 1L based on biology of disease
    • Determining mechanisms of resistance
  • Novel combinations in I/O pre-exposed patients

Mesothelioma

  • Novel combination in 1L and in 2L
    • 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

Merkel Cell Carcinoma

  • Novel combinations in Merkel cell carcinoma (including neoadjuvant)

Innovative Strategies

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

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 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 clear cell and non-clear cell histologies, who are treatment naïve and patients who received prior treatment (including IO and/or TKI).
  • Studies that 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
      • Pathways
        • Angiogenesis, hypoxia, epithelial-mesenchymal transition (EMT), antigen presentation and machinery
  • 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 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, 2019 January 2020 February 2020
March 31, 2020 April 2020 May 2020
June 30, 2020 July 2020 August 2020
September 30, 2020 October 2020 November 2020
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.