Abstract A10: Soluble CD25 and C-reactive protein predict overall survival in melanoma patients receiving anti-CD40 monoclonal antibody CP-870,893 (αCD40) and anti-CTLA4 monoclonal antibody tremelimumab

Purpose: Identifying baseline patient biomarkers that predict clinical outcomes to cancer immunotherapy is a major goal for the field. In a phase I dose escalation study of αCD40 CP-870,893 (0.1-0.2 mg/kg) and tremelimumab (6-15 mg/kg) for patients (pts) with metastatic melanoma, we determined associations between pre-treatment clinical (stage, LDH) and immune variables and tumor response, progression-free survival (PFS) and overall survival (OS). Methods: Twenty-two metastatic melanoma pts (6 stage 4a, 6 stage 4b and 10 stage 4c) enrolled and contributed serum specimens for immunologic evaluation, which included: soluble CD25 (sCD25), C-reactive protein (CRP), EGF, HGF, VEGF, IFNα, IFNγ, TNFα, G-/GM-CSF, MIP1A/1B, MIG, MCP1, IL1B, IL1RA, IL2, IL4, IL5, IL6, IL8, IL10, IL12 and IL13. There were 6 responders (2 CR, 4 PR) and 16 nonresponders (3 SD, 13 PD). With a median follow-up of 26 months (mos), 13 pts have died. Median PFS and OS were 2.5 and 26.1 mos, respectively. Associations with continuous and binary immune variables were tested, cut points for the latter were determined by median or classification and regression tree (CART) analysis. Univariate logistic or Cox regression analyses determined predictors for response or PFS and OS, respectively. Variables with univariate significance Results: Tumor Response. Response was associated with stage (50% in 12 stage 4a/b pts vs 0% in 10 stage 4c pts, p=0.02). Baseline LDH was not associated with response or PFS. No immune variables predicted response. Overall Survival. sCD25 (p=0.01), CRP (p=0.005), LDH (p=0.006) and stage (p=0.01) were highly significant predictors of OS. Natural log transformed sCD25 was highly correlated with CRP (r=0.56, p=0.006) and moderately correlated with LDH (r=0.41, p=0.06) and stage (rho=0.32, p=0.09). CART analysis identified sCD25 >110 and CRP >7 as the optimal cut points for OS. Accordingly, binary sCD25 (>110 vs 7 vs 110, 5 had CRP >7 and of 16 pts with sCD25 110 (or CRP >7), median OS was 4.6 mos. Moreover, binary sCD25 remained highly significant (HR=11.2, p=0.002) after adjusting for LDH (p=0.06). Progression-free Survival. Stage (p=0.01) and sCD25 (p=0.02), but not CRP (p=0.10), were significant predictors of PFS. Binary sCD25 defined by median (>60 vs 7 vs Conclusion: sCD25 and CRP are both highly significant predictors for OS, although they are not independent predictors due to their strong co-linearity. sCD25 remains a significant predictor for OS after adjusting for baseline LDH. To confirm these findings, sCD25 and CRP should be investigated as possible predictive biomarkers in future studies of immune checkpoint inhibitors. Citation Format: Rosemarie Mick, David Bajor, Lee Richman, Robert Vonderheide. Soluble CD25 and C-reactive protein predict overall survival in melanoma patients receiving anti-CD40 monoclonal antibody CP-870,893 (αCD40) and anti-CTLA4 monoclonal antibody tremelimumab. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr A10.