Investigator-initiated studies (IIS) are studies initiated, developed, designed, and managed by a qualified sponsor who assumes sole responsibility for conduct and management of the study (including regulatory obligations, etc). Istari will consider working with a broad range of sponsors including but not limited to the following:

• Academic medical centers
• Individual investigators/researchers
• Collaborative study groups
• Networks and cooperative groups
• Healthcare providers and institutions
• Government research institutions

Support for an approved IIS may come in various forms including supplying drug products, funding, materials, and/or information as allowed under local laws and regulations. Projects proposing provision of external support will also be considered (eg, grant or institutional funding, materials, use of core services, and support provided by other collaborators/organizations).

The following are not considered investigator-initiated studies: access to investigational medicines through compassionate use or expanded access. Details on these programs can be found here.

All investigator-proposed research must offer meaningful scientific and/or clinical objectives supported by clear and valid study designs in which the privacy rights, safety, and welfare of participants is of paramount importance, as applicable.

Requirements of a sponsor/investigator for Istari to consider supporting an IIS proposal include but are not limited to the following:

• Is qualified in terms of background, education, and experience to conduct and complete the proposed research
• Is not debarred, disqualified, restricted, or excluded from engaging in activities relating to development or approval of drugs by any regulatory authority
• Relevant license is current if research involves treatment of patients
• Assumes all responsibilities and obligations to comply with all relevant laws and regulatory requirements (eg, Good Clinical Practice and safety reporting regulations)
• They or their appointed representative holds the IND or equivalent clinical trial authorization (as applicable)
• Agrees to the terms and conditions outlined when submitting the proposal and the final research agreement, which includes but is not limited to the following:
  • Provides safety reports to Istari in accordance with the research agreement
  • Provides study status updates in accordance with the research agreement
  • Submits the final study report and manuscript, as applicable, and in accordance with the research agreement

Istari’s general areas of strategic interest include but are not limited to IIS in the following areas:

• Clinical investigations of efficacy and safety in solid tumors, alone or in combination with immune checkpoint inhibitors or other therapies or procedures, with Istari assets still in development (eg, phase 1 to phase 3 clinical studies)
  • Priority consideration will be given to those with direct intratumoral administration in cutaneous, subcutaneous, or nodal lesions or those that are amenable to injection (eg, via ultrasound guidance), including those amenable to convection enhanced delivery into brain lesions
  • This could include window of opportunity studies and studies inthe neoadjuvant or adjuvant treatment settings
    • Note: clinical applications involving administration into the viscera/deep tissue may require additional consideration
  • Translational research studies including but not limited to the following:
    • Immune cell activation in the tumor microenvironment (injected and noninjected lesions) and periphery
    • Tumor, immune cell, or humoral markers associated with immune activation and/or antitumor response
    • Investigations providing additional mechanistic insight with PVSRIPO alone or in combination with other therapies in solid cancers
  • Nonclinical or animal investigations
    • Note: appropriate institutional and other relevant clearance per current guidance (eg, CDC, WHO GAPIII) is required to allow use of lerapolturev (a live poliovirus vaccine-based recombinant virus) in the nonclinical research setting
    • If cleared, proof-of-concept studies for future clinical applications or those proposing investigations that may yield critical mechanistic or other insight may be considered

There are 3 main steps in our IIS approval process, and our medical science personnel are available to guide you.

• Discuss concept with medical affairs team

  Contact us to request a consult or discuss with your existing clinical or scientific affairs contact. Your representative will discuss your concept with the core IIS review team and provide you with feedback. If there is interest, a concept form (see example) and instructions on how to submit your initial concept proposal in the IIS portal will be provided.

• Submit your preliminary concept

  Submit the details of your proposed concept in the IIS portal for consideration by the study review team.

• Submit final proposal

  If your proposed concept is approved, you will be provided with the application and link to submit the full proposal with additional details, including final protocol and other pertinent information as applicable (eg, informed consent) and an itemized budget via the IIS portal.

Proposals will be reviewed and approved based on scientific merit and alignment with Istari’s areas of strategic interest. We evaluate all funding requests against local fair market value. Funding requests for expenses not associated with the conduct of the study are strictly prohibited.

Accepted projects will then move through the following stages:

• Start-up
• Conduct
• Close-out

Please contact us or your known Istari clinical or scientific representative with any questions.