Phase I Study of CIGB-300 AdministeredIntravenously in Patients with Relapsed/Refractory Solid Tumors

Background: CIGB-300 is an anti-CK2 peptide previously tested by intralesional injections. Here, we explored tolerability, drug accumulation ratio and clinical benefit of intravenous CIGB-300 in patients with relapsed/refractory solid tumors. Methods: A multicenter and open-label phase I study. CIGB-300 administration was performed during 15 min once daily on days 1-5 in alternate weeks until completing three cycles. Stage 1 aimed to determine Maximum Tolerated Dose (MTD) and dose-limiting toxicity (DLT) in dose-escalation (0.2-1.6 mg/kg) while stage 2 explored drug accumulation ratio comparing Cmax and AUC0-12 from first and fifth infusions with 1.6 mg/kg of CIGB-300. Clinical benefit was assumed if patients lived ≥ 6 months. Results: In total, 16 patients were enrolled. Neither MTD nor DLT was observed. The most frequent adverse events were those related to mild allergic syndrome (61.6%) whose magnitude behaved dose-dependently. Drug accumulation ratio between infusions #1 and #5 was 1.0. Twelve patients (75%) lived >6 months and seven patients (43.7%) lived ≥ 12 months after CIGB-300 monotherapy. Four patients died before 6 months. Conclusion: Intravenous administration of CIGB-300 1.6 mg/kg is recommended to be tested in Phase 2-3 trials in patients with either relapsed/refractory NSCLC or breast cancer. Efficacy of once versus twice-daily CIGB-300 administrations can be also compared in upper phase trials.