Poster Presentation 35th Lorne Cancer Conference 2023

A novel Focal Adhesion Kinase inhibitor AMP945 for first-line treatment of pancreatic cancer (#126)

Terrie-Anne Cock 1 , Anthony Bishop 1 , Kendelle Murphy 2 , Paul Timpson 2 , David Herrmann 2 , John N Lambert 1 , Christopher J Burns 1 , Mark Devlin 1 , Nicole Kruger 3 , Jason Licklite 4 , Warwick Tong 1
  1. Amplia Therapeutics, Melbourne
  2. Garvan Institute , Sydney
  3. NMK Consulting, Melbourne,
  4. Nucleus Network, Melbourne

AMP945 is a small molecule, selective and orally bioavailable inhibitor of Focal Adhesion Kinase (FAK). FAK plays a key role in tumor cell growth, particularly immunosuppression, cancer cell invasion and metastasis and also contributes to multiple mechanisms underlying fibrosis. FAK has been associated with the activity of myofibroblasts and collagen deposition and remodelling in pancreatic cancer. Accordingly, FAK inhibitors designed to target unique aspects of the tumour microenvironment offer promising new clinical opportunities for improving patient survival in both pancreatic cancer and other highly fibrotic cancer types.

In preclinical studies, AMP945 displays potent anti‑fibrotic activity in vitro and in vivo. In mouse models of pancreatic cancer, pulsed dosing of AMP945 added to gemcitabine/nab‑paclitaxel inhibited collagen deposition and cross-linking and potentiated the effect of chemotherapy leading to increased survival.

A randomized, double-blind, placebo-controlled single ascending dose (SAD) and multiple ascending dose (MAD) Phase 1 clinical trial of AMP945 has been completed in healthy volunteers. In the trial, AMP945 showed excellent safety, tolerability, and pharmacokinetic properties. Importantly, AMP945 demonstrated dose- and exposure-dependent pharmacodynamic evidence of target engagement through measurement of FAK activity (phosphorylation; p-FAK) in skin biopsies.

Amplia’s recently initiated Phase 1b/2a clinical trial (ACCENT, NCT05355298) is assessing a pulsed dosing regimen of AMP945 in combination with gemcitabine and nab‑paclitaxel standard of care as first-line therapy in patients with advanced pancreatic cancer. In the ACCENT trial, patients will receive a one-week oral loading dose of AMP945 and will be pulse dosed for four days prior to administration of gemcitabine and nab-paclitaxel, given according to a standard treatment schedule. Once daily oral dosing has anticipated benefits in terms of limitation of risk of acquired resistance, minimal potential for drug-drug interactions, adherence to therapy, and allows patients to self-administer AMP945 with the aim of potentiating response to standard of care chemotherapy.

This presentation will describe the preclinical and clinical evidence gathered so-far that supports progression of AMP945 combination therapy in patients with advanced pancreatic cancer.