1. Letters of Intent (LOIs) Through the NCI’s Cancer Therapy Evaluation Program (CTEP) Dr. Patricia M. LoRusso, D.O. Karmanos Cancer Institute Wayne State University

2. Benefits of the CTEP LOI Allows investigators to perform clinical instead of clinical Allows investigators to perform clinical research instead of clinical trials Allows access to exciting novel agents Allows access to exciting novel agents Potential for novel-novel combination Potential for novel-novel combination Potential combinations from different companies Potential combinations from different companies CTEP holds the IND, less paperwork CTEP holds the IND, less paperwork Novel trial designs Novel trial designs Investigator initiated studies important for CCSGs Investigator initiated studies important for CCSGs Successful competition attractive to funding agencies Successful competition attractive to funding agencies

3. The NCI-CTEP LOI Required to conduct clinical trial with CTEP IND agents Required to conduct clinical trial with CTEP IND agents Solicited - submitted in response to development plan designed by CTEP Investigational Drug Steering Committee (IDSC) and industry collaborator Solicited - submitted in response to development plan designed by CTEP Investigational Drug Steering Committee (IDSC) and industry collaborator Unsolicited - submitted to address novel hypotheses supported by published or unpublished preclinical data Unsolicited - submitted to address novel hypotheses supported by published or unpublished preclinical data

4. Correlative Studies Correlative studies provide a better understanding of the effects of agents on their tumor targets Correlative studies provide a better understanding of the effects of agents on their tumor targets Pharmacokinetics Pharmacokinetics Pharmacodynamics Pharmacodynamics Pharmacogenetics Pharmacogenetics Biomarker analyses Biomarker analyses Molecular Profiling Molecular Profiling Each correlate should include rationale, hypothesis, and methods Each correlate should include rationale, hypothesis, and methods

5. Tips for a successful LOI START EARLY AND GIVE YOURSELF ENOUGH TIME!! START EARLY AND GIVE YOURSELF ENOUGH TIME!! Gather a team to help in design: Gather a team to help in design: clinicians clinicians scientists scientists statisticians statisticians budgetary specialists budgetary specialists Design aims / hypotheses in conjunction with a biostatistician Design aims / hypotheses in conjunction with a biostatistician Consider funding – if approved, is there $ to actually carry out the work? Consider funding – if approved, is there $ to actually carry out the work? Remember quality is the key – not quantity Remember quality is the key – not quantity

6. The Value of Partnerships Collaboration with other institutions allows: Collaboration with other institutions allows: Better science Better science Increased patient recruitment Increased patient recruitment Intellectual input Intellectual input Momentum Momentum

7. More tips Don’t be afraid to think outside the box!!! Don’t be afraid to think outside the box!!! Be creative Be creative Schedule meetings far in advance Schedule meetings far in advance Be mindful of the deadline Be mindful of the deadline Don’t be on an island – ask for help! Don’t be on an island – ask for help! CTEP is there to help you!!!!! CTEP is there to help you!!!!!

8. What I HATE about writing an LOI It takes a lot of time to write It takes a lot of time to write It competes with other commitments It competes with other commitments You don’t always get them!!!! You don’t always get them!!!! It is critical to learn from your failures!!!! It is critical to learn from your failures!!!!

9. What I LOVE about writing an LOI Creative fun Creative fun Allows translation of the science Allows translation of the science Allows collaboration Allows collaboration Leadership, negotiation and organization Leadership, negotiation and organization Helps organize and focus concepts Helps organize and focus concepts Often can lead to grant funding Often can lead to grant funding Exciting Exciting

10. The beauty of this process is to allow you to perform clinical instead of simply clinical The beauty of this process is to allow you to perform clinical research instead of simply clinical trials

11. Thank you!