Efficacy of SBP-101, in combination with gemcitabine and nab-paclitaxel, in first-line treatment of metastatic pancreatic ductal adenocarcinoma.

Abstract

710 Background: SBP-101, a polyamine metabolic inhibitor, inhibited growth in 6 human pancreatic ductal adenocarcinoma (PDA) cell lines and 3 murine xenograft tumor models of human PDA. SBP-101 monotherapy in heavily pre-treated PDA patients (> 2 prior regimens, N=4) showed a median survival of 5.9 months at the optimal dose level. Purpose: To assess the safety, tolerability, PK, and efficacy of SBP-101 in combination with gemcitabine (G) and nab-paclitaxel (A) in patients with previously untreated metastatic PDA. Methods: In a modified 3+3 dose escalation scheme, subcutaneous injections of SBP-101 were dosed at 0.2, 0.4 or 0.6 mg/kg days 1-5 of each 28-day cycle. G (1000 mg/m2) and A (125 mg/m2) were administered intravenously on Days 1, 8, and 15 of each cycle. Safety and tolerability were evaluated by clinical and laboratory assessments. PK was evaluated on day 1 of cycle 1. Efficacy was assessed by CA19-9 levels, objective response as assessed by RECIST criteria, progression-free survival (PFS) and overall survival (OS). Results: Fifteen patients have been enrolled in 3 cohorts (1: N=4, 2: N=7, 3: N=4) and received up to 6 cycles of treatment (7 subjects are ongoing in cohorts 2 and 3). The most common adverse events related to SBP-101 are fatigue (N=4), nausea (N=2) and injection site pain (N=2). There is no evidence of SBP-101-related bone marrow suppression or peripheral neuropathy. One patient in cohort 2 developed grade 3-4 reversible liver enzyme elevation. PK parameters in cohort 1 were below the limits of detection at most time points, but plasma Cmax and AUC0-t were measurable in cohorts 2 and 3. In those cohorts, CA19-9 levels decreased 76-95% in 7 of 8 evaluable subjects (1 additional subject TBD), with 5 patients achieving partial responses (4 ongoing) and 1 achieving stable disease. Median PFS and OS have not yet been reached. Conclusions: Preliminary results suggest SBP-101 is well tolerated when administered with G and A. Signals of efficacy support continued development of SBP-101 in combination first-line treatment for PDA. Clinical trial information: NCT03412799.