NYU Melanoma SPORE

OVERALL PROJECT SUMMARY The impressive clinical successes in immune checkpoint inhibition (ICI) therapy over the last decade have not been matched by the development of clinically useful tools to predict patient response and toxicity. The integration of biomarkers of patient outcome and toxicity into clinical care would allow more optimal treatment

selection. The primary objective of the New York University (NYU) Melanoma SPORE is to address the urgent need to develop and validate clinically useful, personalized biomarkers to optimally administer immune checkpoint inhibition therapies in the adjuvant setting. We have chosen to concentrate our efforts in this area

because FDA approval of immunotherapies in this clinical context has led to a significant increase in the utilization of these treatments with expansion of adjuvant trials to other cancers. The use of adjuvant ICI will alter the immunobiology of melanoma and other malignancies as well. Identifying biomarkers of benefit and toxicity is

critical, timely, and promises to have broad applicability. We have made significant progress towards these aims. In the first five years of funding, we published 155 papers (82 SPORE-related, 15 are inter-SPORE collaborative publications); generated an additional 4 team science awards; developed a pre-treatment auto-antibodies

signature that can predict toxicity and recurrence; and supported 20 DRP and CEP awardees. The extension of support for the NYU Melanoma SPORE for a sixth year with interim funding will facilitate the continuation of these efforts and maintenance of our translational infrastructure to sustain progress towards our competitive

renewal. We therefore request interim funding for Projects 2 and 3 as well as support for the Administrative Core A and the Biospecimen Core B. While continued funding for Cores A and B are necessary to maintain the functional infrastructure that is a core strength of our program, Project 2 and 3 were selected both for the impact

of their ongoing work and their direct relevance to the competitive renewal. Project 1 of the competitive renewal is the continuation of our current Project 3, which is focused on understanding the predictive power of serum autoantibodies to determine response and toxicity and the underlying biology of toxicity. Project 2, which has

extracted novel genomic biomarkers of response in the setting of adjuvant therapy, directly supports both Projects 1 and 3, where multi-omic approaches will be used to dissect tissue-based and peripheral immune determinants of both response and toxicity. With this support we will therefore continue to advance our efforts to

solve pressing needs in the melanoma field, with the expectation that our insights can be extended to the increasing number of ICI--treated cancers.