Phase Ib clinical study of CBP501, cisplatin, and nivolumab administered every three weeks in patients with advanced refractory tumors: Efficacy in dose-escalation and expansion cohorts.

Abstract

3059 Background: CBP501 is a 12-amino acid G2 checkpoint abrogator and calmodulin-modulating peptide that increases platinum influx into tumor cells and induces tumor immunogenic cell death. CBP501 also suppresses platinum-induced release of cytokines by macrophages, lowers cancer stem cell populations, and reduces migration, invasion, and epithelial-mesenchymal transition of tumor cells. We report safety and efficacy outcomes from dose-escalation and expansion cohorts of a Phase Ib study of CBP501 combined with cisplatin and nivolumab (NCT03113188). Methods: An open-label Phase I trial was conducted using a 3+3 design: CBP501 and cisplatin were dosed simultaneously by 1h infusion Q3W at 4 different combined dose levels (CBP501: 16 or 25 mg/m2; cisplatin: 60 or 75 mg/m2) in the dose-escalation cohort. Nivolumab (240 mg) was dosed on the same day as a 1h infusion following CBP501/cisplatin. CBP501 and cisplatin were fixed at 25 and 60 mg/m2, respectively, in the expansion cohort. Eligible patients had pathologically confirmed, locally advanced or metastatic solid tumors, age ≥18 years, ECOG PS 0-1, life expectancy > 3 months. The dose-expansion cohort had pretreated metastatic exocrine pancreatic cancer or microsatellite stable colorectal cancer (CRC). Scans were performed every 6 weeks while on study, then every 3 months. Results: The most common related adverse events (AEs) were infusion-related reaction (rash, itching, hives; n = 32/37 [Gr 1, n = 4; Gr 2, n = 28]; 86%) and anemia (n = 19/37 [Gr 1/2, n = 10; Gr 3, n = 9]; 51%). There were no additional safety signals other than those known for each agent. At January 9, 2020 (interim analysis), efficacy was evaluable in 17/19 patients in the dose-escalation cohort. Unconfirmed partial response was seen in 18% (3/17; 1 pancreatic, 1 colorectal, 1 cholangiocarcinoma), with > 3 months stable disease (SD) in 41% (7/17), disease control in 41% (7/17), and > 8 months overall survival (OS) in 53% (9/17). In the expansion cohort, efficacy was evaluable in 8/13 patients with pancreatic cancer: > 4 months SD was 50% (4/8), median progression-free survival 4.2 months, and median OS 5.9 months (6/8 ≥3rd line). The CRC cohort median OS for all CRC patients (n = 10) including the dose-escalation cohort (n = 5) was 17.5 months (10/10 ≥3rd line). Conclusions: The triple-drug combination is reasonably tolerable with preliminary signs of efficacy in refractory solid tumors, including those in which cisplatin and nivolumab have limited single-agent activity. Clinical trial information: NCT03113188 .