Dendritic-cell vaccine (DCVAC) with first line chemotherapy in patients with stage IV NSCLC primary analysis of phase 2, open-label, randomized, multicenter trial.
ABSTRACT
Background: Immunotherapy for induction of tumor cell specific immune responses destroying tumor cells, has emerged as a promising treatment modality in lung cancer (LuCa). Autologous DCVAC can present tumor antigens to elicit a durable immune response. We hypothesized that adding DCVAC to the standard of care chemotherapy (ct) could prolong progression-free survival (PFS) and overall survival (OS).
Methods: This study evaluated the efficacy and safety of DCVAC/LuCa (active cellular immunotherapy based on dendritic cells) concomitantly added to ct (carboplatin/paclitaxel) – Arm A (A) vs DCVAC/LuCa + immune modulators (IFN-α and hydroxychloroquine) – Arm B (B) vs ct – Arm C (C) in NSCLC patients (pts). Randomization 1:1:1; pts in A and B received up to 15 doses of DCVAC, ct was given 4-6 cycles in A and C. Stage IV NSCLC was confirmed histologically or cytologically, ECOG 0-1 pts were eligible. Stratification was done by histology subtype and smoking history. Primary efficacy analysis compared A vs C only as enrollment to B was closed early based on Sponsor’s assessment of further clinical development potential, there were no safety concerns or signals.
Results: 112 pts at 12 sites were randomized (A/45 B/29 C/38). Patients characteristics were comparable across the study groups with the exception of gender (m/f, %: 50/50 (A) and 26/74 (C) and smoking history (75 % of smokers in A, 97 % in C). Median follow up time was 14.1 months, range 0.032-29,765. Median OS was 15.5 months in A compared to 11.8 months in C, hazard ratio (HR) 0.56, p-value 0.05, 95% CI, data maturity 65%. Median PFS was 6.73 in A and 5.65 months in C HR 0.64, p-value 0.05, 95% CI, data maturity 81%. Overall response rate was 45% in A vs 22.9% in C. Most TEAEs were related to ct (anemia [37%-A, 32%-C], neutropenia [48% in A, 21%-C], thrombocytopenia [28% in A, 27% in C]). There were no grade ≥ 3 TEAEs solely related to DCVAC. Most common leukapheresis-related AEs were haematoma and hypotension.
Conclusions: Addition of DCVAC-based immunotherapy to the standard of care chemotherapy significantly improved OS in stage IV NSCLC. Clinical trial information: EudraCT 2014-003084-37.