Phase II study of CIMAvax EGF plus nivolumab in previously treated, immunotherapy-naïve advanced NSCLC

CIMAvax-EGF is a novel epidermal growth factor (EGF)-depleting therapy that induces the development of anti-EGF antibodies to clear free serum EGF from circulation. The primary objective of this single-arm phase II trial (NCT02955290) was to evaluate 12-month overall survival (OS) in patients receiving CIMAvax-EGF and Nivolumab for previously treated, immunotherapy-naïve advanced NSCLC. Patients received 2.4 mg of CIMAvax-EGF intramuscularly every 2 weeks for four doses (loading phase) then continued monthly maintenance. Nivolumab was given 240 mg intravenously every 2 weeks. OS and progression-free survival (PFS) data were determined using a Kaplan–Meier test with 95% confidence intervals. Twenty-one pts completed the loading phase (PP). Disease control rate was 47.6% ( n = 10). The PP patients had a 48% 12-month OS and 29% 3-year OS rate. Median OS for PP pts was 11.9 months. Ability to inhibit EGFR phosphorylation using individual patient post-vaccination available sera correlated with survival, with greater inhibition associated with longer median OS (11.3 vs 6.5 months). Median OS, 1-yr and 3-yr OS for EGFR/ALK/KRAS wild-type pts were 31.7 months, 67%, 50%, respectively, and 10.1 months, 29%, 0%, respectively, in KRAS mutated pts. The combination of CIMAvax-EGF and nivolumab demonstrated improved survival compared to historical nivolumab monotherapy cohorts. Patients with EGFR/ALK/KRAS wild-type tumors derived greatest benefit. Sera collected after CIMAvax-EGF loading phase showed inhibition of EGFR phosphorylation, and higher level of inhibition correlated with longer survival. These findings suggest that CIMAvax-EGF is feasible to combine with PD-1 blockade and may have additive activity, particularly in EGFR/ALK/KRAS wild-type NSCLC.