Integrative Analysis of Prognostic Factors to Neoadjuvant Nivolumab/CMP-001 in Stage III B/C/D Melanoma
Diwakar Davar, MD
|Co-PI||Meghan Mooradian, MD; Julie Stein, MD|
|Mentor||Hassan Zarour, MD; Ryan Sullivan, MD; Janis Taube, MD, MSc|
|Award Type||Team Awards|
|Institution||University of Pittsburgh|
|Donor Support||MRF Breakthrough Consortium-Bristol Myers Squibb Young Investigator Research Team Award to Advance the Field of Translational Immuno-Oncology|
Patients with lymph-node positive melanoma have a high risk of recurrence despite curative surgery. While adjuvant therapy given after surgery improves RFS and OS, ~25% of patients particularly those with bulky lymph-node disease, progress prior to commencing adjuvant therapy.
Neoadjuvant immunotherapy with anti-PD-1 produces pathologic responses in 25-30% of patients and is well tolerated. While combinations of anti-PD-1 with anti-CTLA-4 produce even greater pathological response rates, this combination is associated with considerable side effects in >50% of treated patients. Combinations that improve upon the benefit seen with anti-PD-1 with minimal additional side effects are desirable.
Based upon the successes of anti-PD-1/CMP-001 in advanced melanoma, we launched a clinical trial studying CMP/nivo in high-risk resectable melanoma with promising results. In 20 treated patients, we have shown that the neoadjuvant CMP/nivo produces pathologic responses in approximately 70% of patients. The combination is well tolerated with low incidence of adverse events. Patients who experience major pathologic response have prolonged RFS. In this context, we propose a tri-institutional collaboration to analyze immunophenotypic, histopathologic and ctDNA biomarkers of response to this therapeutic modality.