BACKGROUND: The combination of nivolumab with CIMAvax is safe and can be administered together at the approved dosage of each agent administered as monotherapy. We report the analyses on circulating cytokines and putative biomarkers in relation to treatment outcomes.

METHODS: Serial blood samples from 13 patients enrolled during dose-escalation were obtained and analyzed for dynamic changes in serum EGF and anti-EGF antibody (Ab) levels using ELISA-based assays. Circulating cytokines and relevant proteins implicated in EGF signaling were measured using Luminex multiplex bead array assays. Univariate analysis of variance was used to investigate the association between various analytes and treatment outcomes. Spearman rank correlation was calculated to determine the relationship between analytes. Tumor response was assessed using irRECIST and RECIST 1.1.

RESULTS: 54% of enrolled pts had known tumor PD-L1 tumor proportion score (TPS) of 0%. Only 1 pt had PD-L1 TPS > 50%. Objective response rate was 31%, using either irRECIST or RECIST 1.1 criteria (3 pts PD-L1 TPS 0%, 1 pt PD-L1 TPS 60%). All enrolled pts had baseline serum EGF level > 250 pg/ml (mean 550, range 358 to 865) but there was no relationship between baseline EGF levels nor reduction in EGF level with tumor response. There was no difference between baseline levels of EGF-like ligands TGF-alpha, Neuregulin, Heparin-binding EGF according to tumor response. Excluding 2 pts who received less than 3 loading doses of CIMAvax, 82% of pts achieved good anti-EGF Ab titer > 1:4000 by day 43. Responders(R) had lower baseline neutrophil-lymphocyte ratio(NLR, OR 0.31, p=0.077). R had undetectable baseline levels of IFNa2 compared to nonR (mean 6.51 pg/ml, 95% CI 4.04-8.98). Baseline IL-7, IL-15 and CXCL11 levels in R were also lower compared to nonR (mean IL-7, 0.77 [95% CI, 0.54-1.0] vs 4.5 pg/ml [ 95% CI, 2.65 - 6.34]; mean IL-15, 0.95 [95% CI, 0.89-1.0) vs 5.50 pg/ml [95% CI, 3.07- 7.93]); mean CXCL11 20.75 [95% CI, 15.65 - 24.35] vs 87.87 pg/ml [95% CI, 20.38 - 155.37]), respectively. There is significant relationship between baseline levels of CXCL11 with NLR (r=0.59,p=.03)and C-reactive protein (CRP) levels (r=0.76, p=.002) and between CRP with NLR (r=0.71, p=0.006).

CONCLUSIONS: Combination of nivolumab led to more pts achieving a good anti-EGF Ab titer earlier to CIMAVax (compared to historical cohort). Baseline EGF level is not associated with objective tumor response to the combination. Phase II portion of the study is ongoing.

Citation Format: Grace K. Dy, Kelvin Lee, Adrienne Groman, Aileen Cinquino, Carlos Cedeno, Hans Minderman, Alan Hutson, Paul Wallace, Candace Johnson, Zaima Mazorra, Danay Saavedra Hernandez, Kalet Leon, Agustin Lage, Tania Crombet. Final results of the Phase I study of nivolumab in combination with CIMAvax, an epidermal growth factor(EGF)-depleting immunotherapy in patients (pts) with advanced non-small cell lung cancer (NSCLC): Focus on biomarker analyses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT088.