DFP-14323(INN: Ubenimex) is protease inhibitor of aminopeptidase N (also called CD13), originated from Streptomyces olivoreticuli have been used for maintenance therapy of AML in Japan. Aminopeptidase is well known as one of prognostic factors for several cancer patients, including non-small-cell lung cancer (NSCLC). Otherwise, afatinib is one of the standard treatments in non-small-cell lung cancer (NSCLC) patients with EGFR mutation, but the toxicities often require dose adjustment. Recently, it is suggested that reducing afatinib doses can decrease treatment-related adverse events without affecting efficacy. We aimed to examine efficacy of DFP-14323 with low-dose afatinib by conducting phase II study in patients with metastatic NSCLC harboring EGFR mutation.
This study was a multi-center, single-arm, open-label phase II trial. Stage III/IV and treatment-naïve patients with common EGFR mutation-positive(L858R or 19del) NSCLC were treated with afatinib at a starting dose of 20 mg/day and DFP-14323 at a fixed dose of 10mg/day until disease progression or intolerable toxicity. Primary endpoint is disease control rate (DCR) defined by sum of CR, PR and SD (RECIST1.1) and secondary endpoints include progression-free survival, overall response rate and safety. A sample size of 26 patients was estimated based on α error of 0.05 (two sided), β error of 0.20, expected DCR 90% and threshold DCR 70% used the Simon’s two stage design.
From July 2018 to March 2020, 26 patients were enrolled. Median age was 72 years (range, 53-82). Twenty-one patients (81%) were female, and 16 (62%) were never-smokers. Mutation subtypes were half Del-19 and half L858R. As of the data cut-off of June 2020, DCR was 100% (26/26) with 17 confirmed PRs. Grade 3 adverse events were observed in 5 (19.2%,1 diarrhea, 1 stomatitis, 2 paronychia, and 1 dermatitis), and all of these events were related with afatinib. No grade 4 or 5 adverse events were observed.
Combination of DFP-14323 and low-dose afatinib showed promising efficacy and good tolerability. We are planning a phase III study to evaluate this combination therapy after evaluation of PFS.
Clinical trial identification
Legal entity responsible for the study
Delta-Fly Pharma Inc.
Delta-Fly Pharma Inc.
H. Yoshioka: Honoraria (self), a clinical trial coordinator: Delta-Fly Pharma Inc.; Honoraria (self), lecturing: Boehringer Ingelheim. M. Mori, T. Yokoyama, K. Hirano: Honoraria (self), lecture: Boehringer Ingelheim. C-L. Huang: Honoraria (self), a clinical advisor: Delta-Fly Pharma Inc. All other authors have declared no conflicts of interest.