Abstract CT304: Narmafotinib (AMP945) in combination with gemcitabine and nab-paclitaxel in first-line patients with advanced pancreatic cancer (ACCENT trial) a Phase 1b 2a study-Interim analysis

Abstract Background: Narmafotinib (AMP945) is a highly potent and selective inhibitor of Focal Adhesion Kinase (FAK). FAK is a non-receptor tyrosine kinase over-expressed in pancreatic cancer (PCa), where it contributes to cell survival, proliferation, migration, chemoresistance and underlying fibrosis and immunosuppression in the tumor microenvironment. ACCENT (NCT05355298) is a Phase 1b/2a (P1b/2a) trial of narmafotinib in combination with Gem/NabP in metastatic PCa patients. P1b dose escalation was completed, with 400 mg narmafotinib identified as the recommended P2a dose. The P2a study was conducted in Australia and South Korea with interim findings reported below. Methods: The ACCENT trial is an open-label two-part study of the PK, safety and tolerability, and efficacy of narmafotinib in combination with standard Gem/NabP as first-line therapy in patients with metastatic PCa. Gem (1000 mg/m2) and NabP (125 mg/m2) were given on days 1, 8 and 15 of a conventional 28-day cycle. Patients also received daily narmafotinib (400 mg, p.o.) on days -8 to -2 of cycle 1 and then combined as 4-day pulses beginning on days 3, 10 and 24 of each 28-day chemotherapy cycle. The primary endpoint was investigator assessed objective response rate (ORR) by RECIST 1.1. Key secondary endpoints included adverse events (AEs, using NCI CTCAEv5.0), progression free survival (PFS) and overall survival (OS). Results: ACCENT patients treated with 400 mg narmafotinib (P1b/2a, N = 64): ECOG 0-1; median age 62.7; male: 50%. As of 20 January 2026, the ORR was 42% (38% confirmed in evaluable patients), including 1 complete response and 1 partial response later determined as a pathological complete response. Results for many patients show deep reductions in tumor size that are sustained during treatment with 21% of evaluable patients on treatment for >12 mos., including 2 ongoing patients currently at 21 and 18 mos. on study. These benefits translated to improved median OS of 11.1 mos. as well as median duration of response at 6.9 mos. and median PFS of 7.7 mos.; these results compare favorably to the MPACT benchmark study of chemotherapy alone (OS 8.5 mos., DoR 5 mos. & PFS 5.5 mos.). Most common AEs related to narmafotinib were nausea (29%), diarrhea (16%), vomiting (15%), fatigue (11%), gastroesophageal reflux (7%) and constipation (6%), which were predominantly grade 1-2 in severity. Toxicity was similar to that reported for chemotherapy alone. Conclusions: Narmafotinib combined with Gem/NabP met its primary efficacy endpoint whilst having a limited impact on the overall safety and tolerability of chemotherapy. Given narmafotinib is dosed intermittently in this study (12/28 days per cycle), and noting its favorable safety and tolerability profile, subsequent studies including pivotal trials will utilise daily dosing, which may further enhance efficacy. Citation Format: Terrie-Anne Cock, Sumitra Ananda, Choong-kun Lee, Nick Pavlakis, Joon Oh Park, Jin Won Kim, David Lau, Lara Lipton, Adnan Nagrial, Woo Jin Lee, Howard Chan, Do Youn Oh, Warren Joubert, Sarah Kinkel, Nicole Kruger, Charlotte Mulder, Jason Lickliter, Christopher J. Burns. Narmafotinib (AMP945) in combination with gemcitabine and nab-paclitaxel in first-line patients with advanced pancreatic cancer (ACCENT trial) a Phase 1b 2a study-Interim analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT304.