Abstract 332P
Background
Metastatic pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with limited treatment options. Nintedanib is a potent, orally available kinase inhibitor targeting VEGFRs, PDGFRs, and FGFR. Nintedanib inhibits the signaling cascade mediating angiogenesis by binding to the adenosine triphosphate (ATP) binding pocket of the receptor kinase domain. We report results from phase IB study of Nintedanib in combination with chemotherapy gemcitabine (Gem) and nab-paclitaxel (Nab-P).
Methods
This was a single-arm, open label, phase IB study testing the combination of Nintedanib with Gem and nab-P. We used standard 3+3 dose escalation rules for Nintedanib -150 mg twice daily and 200 mg twice daily. Patients received nintedanib monotherapy for a two-week run-in period followed by Nintedanib plus standard dose Gem and nab-P. Primary end point was to determine safety and tolerability with Gem and nab-P. Secondary end point was to determine preliminary efficacy (overall response rate (ORR), progression free survival (PFS) and overall survival (OS).
Results
13 patients were enrolled from November 2017 to September 2020. The median age was 66 years (range, 52-75). 53% were male and 47% female.12 patients were white, one patient did not disclose. Median duration of follow up was 7.7 months (range, 2-15) months. The most common adverse events during the single agent nintedenib run-in were all grade 1-2 and included nausea (15%), vomiting (15%), fatigue (15%), and loss of appetite (15%). The most common adverse events (any grade) with Nintedanib + chemotherapy were anemia (69%), neuropathy (61%), fatigue (61%), and neutropenia (53%). The most common grade 3-4 treatment related adverse events were neutropenia (23%). The maximum tolerated dose of nintedanib was 200 mg twice daily. The objective response rate by RECIST 1.1 was 15% (one partial and one complete response). Median PFS was 5.0 months (95% CI, 3.8 to 7.3). Median OS was 7.8 months (95% CI, 4.6 to 14.9) months.
Conclusions
Nintedanib 200 mg twice daily was safe and well tolerated as monotherapy and in combination with gem and nab-p. Future studies will be needed to confirm its efficacy in patients with metastatic PDAC.
Clinical trial identification
NCT02902484.
Legal entity responsible for the study
UT Southwestern Clinical Research Office, Boehringer Ingelheim Pharmaceuticals, Inc.
Funding
Boehringer Ingelheim Pharmaceuticals, Inc.
Disclosure
All authors have declared no conflicts of interest.