Abstract CT087: Narmafotinib (AMP945) in combination with gemcitabine and nab paclitaxel in first-line patients with advanced pancreatic cancer (ACCENT trial) a phase 2a study: Interim analysis

Abstract Background: Narmafotinib is a highly potent and selective, orally bioavailable inhibitor of Focal Adhesion Kinase (FAK). FAK is a non-receptor tyrosine kinase over-expressed in pancreatic cancer, where it contributes to cell survival, proliferation, migration and chemoresistance and thus plays a key role in tumour growth. FAK also contributes to multiple mechanisms underlying fibrosis and immunosuppression in the tumor microenvironment. A Phase 1b/2a trial - the ACCENT trial - investigates narmafotinib in combination with gemcitabine and nab-paclitaxel in advanced pancreatic cancer patients; Phase 1b is complete, with Phase 2a currently underway in Australia and South Korea. Methods: The ACCENT trial (NCT05355298) is an open-label two-part study of the pharmacokinetics (PK), safety and tolerability, and efficacy of narmafotinib in combination with standard gemcitabine and nab-paclitaxel (Abraxane®) as first-line therapy in patients with advanced pancreatic cancer. Patients received narmafotinib as monotherapy on days -8 to -2 and then again as 4-day pulses beginning on days 3, 10 and 24 of each 28-day chemotherapy cycle. In Part A, patients were enrolled in a 3+3 combination design with sequentially escalating doses of narmafotinib (100, 200 or 400 mg, qd) to identify a suitable Phase 2 dose. Narmafotinib plasma PK was assessed during monotherapy and Cycle 1. Imaging was conducted every 2 months and evaluated using RECIST 1.1. Part B utilizes a Simon’s two-stage design at 400 mg narmafotinib, with the primary objectives of assessing safety, tolerability and efficacy of the combination. Results: Preliminary Phase 1b (Part A) analysis across all doses (14 patients) showed narmafotinib to be generally safe and well-tolerated with promising signs of efficacy indicating a dose-dependent increase in duration of treatment and best response. Five confirmed partial responses (4 at 400 mg narmafotinib; 1 at 200 mg) were recorded and 4/6 patients on 400 mg narmafotinib received treatment for >6 months. A dose of 400 mg qd of narmafotinib was selected for the Phase 2a (Part B) study. Preliminary Part B analysis from the initial 26 patients showed narmafotinib to be generally safe and well-tolerated with promising signs of efficacy, with 10 confirmed partial responses observed to date. The median duration on trial (DoT) continues to demonstrate a significant improvement over the historical gemcitabine+nab-paclitaxel combination. Narmafotinib continues to be well-tolerated. Common treatment-emergent adverse events (TEAE) were predominately mild to moderate and included nausea (20.5%), diarrhea (12.8%) and gastroesophageal reflux disease (10.3%). Conclusions: Preliminary Part B analysis on the initial 26 patients showed narmafotinib to be safe and well-tolerated with promising signs of efficacy. Citation Format: Terrie-Anne Cock, Sarah Kinkel, Nicole Kruger, Charlotte Mulder, Ananda Sumitra, Marion Harris, Warren Joubert, Lara Lipton, Adnan Nagrial, Nick Pavlakis, Jin Won Kim, Choong-kun Lee, Do-Youn Oh, Joon Oh Park, Woo-Jin Lee, Jason Lickliter, Christopher Burns. Narmafotinib (AMP945) in combination with gemcitabine and nab paclitaxel in first-line patients with advanced pancreatic cancer (ACCENT trial) a phase 2a study: Interim analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT087.