Amplia Therapeutics Preclinical Data Shows Narmafotinib Boosts KRAS Inhibitors
Key Takeaways
Amplia narmafotinib KRAS cancer data presented at AACR 2026 shows the FAK inhibitor enhances KRAS inhibitor activity across pancreatic, lung, and ovarian cancer models, potentially unlocking major partnership opportunities.
- Amplia Therapeutics presented preclinical data at the AACR Special Conference on 6 March 2026 showing narmafotinib enhances KRAS inhibitor activity across pancreatic, lung, and ovarian cancer models.
- In a KRAS inhibitor-insensitive lung cancer model, narmafotinib combined with adagrasib restored tumour responsiveness, suggesting utility in cancers with limited initial response to KRAS inhibition alone.
- The ACCENT trial has recorded a 35% confirmed objective response rate in first-line advanced pancreatic cancer patients, comparing favourably to the 23% benchmark rate for chemotherapy alone.
- Management is actively pursuing discussions with pharmaceutical and biotechnology companies working across the more than 50 KRAS inhibitor programmes currently in global clinical development.
- A second trial, AMPLICITY, has recently opened in Australia and the United States, broadening narmafotinib's clinical development programme beyond the ACCENT trial.
Amplia presents preclinical data showing narmafotinib enhances KRAS inhibitor activity
Amplia Therapeutics (ASX: ATX) has presented Amplia narmafotinib KRAS cancer data at the AACR Special Conference on RAS Oncogenesis and Therapeutics in Los Angeles on 6 March 2026. The poster presentation disclosed preclinical findings demonstrating that the company’s lead drug candidate, narmafotinib, enhances the activity of KRAS inhibitors across multiple cancer models, including pancreatic, lung, and ovarian cancer.
The data indicates that narmafotinib blocks resistance pathways that can emerge during KRAS inhibitor treatment, potentially enhancing both efficacy and durability of response. This positions the therapy within a high-activity drug development space, with over 50 KRAS inhibitors currently in clinical studies globally.
Dr Chris Burns, CEO
“We are excited to present our research findings at this specialist conference focused on RAS inhibition in cancer. We believe there is significant clinical potential in combining narmafotinib with kRAS inhibitors and will be discussing our findings with pharma and biotech companies actively working in this space.”
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What are KRAS inhibitors and why does resistance matter?
KRAS inhibitors represent a new class of targeted cancer therapy designed to block mutant KRAS proteins, which drive tumour growth in lung, colon, and pancreatic cancers. These mutations are among the most common genetic alterations found in solid tumours, making KRAS inhibitors a priority area for drug development.
Despite promising mid-stage clinical data, KRAS inhibitors face two critical challenges:
- Treatment-emergent resistance is commonplace, limiting the duration of clinical benefit
- Side effects can be significant, potentially requiring dose reductions or treatment discontinuation
Narmafotinib’s mechanism as a FAK (Focal Adhesion Kinase) inhibitor targets one of these resistance pathways. By blocking FAK signaling, which becomes hyperactivated when KRAS is inhibited, the combination approach aims to prevent or delay resistance whilst maintaining treatment efficacy.
Preclinical results across multiple cancer models
The poster presentation covered combination studies in xenograft models representing three distinct cancer types, each harbouring different KRAS mutations.
| Cancer Type | Model | KRAS Mutation | Combination Partner |
|---|---|---|---|
| Ovarian | TOV-21G | G13C | Pegylated liposomal doxorubicin (PLD) |
| Pancreatic | Capan-1 | G12V | Gemcitabine/nab-paclitaxel |
| Pancreatic | MIA PaCa-2 | G12C | Daraxonrasib |
| Lung | NCI-H2122 | G12C | Adagrasib |
In the TOV-21G ovarian cancer model (KRASG13C), combining narmafotinib with pegylated liposomal doxorubicin produced enhanced tumour reductions compared to chemotherapy alone. Expression profiling revealed that narmafotinib disrupted the RAS/ERK/MAPK signaling axis and dampened Myc-responsive proliferation programmes.
The pancreatic cancer models demonstrated prolonged tumour inhibition when narmafotinib was combined with standard chemotherapies or KRAS inhibitors. In the Capan-1 model (KRASG12V), the combination with gemcitabine and nab-paclitaxel extended the duration of tumour control. The MIA PaCa-2 model (KRASG12C) showed improved response when narmafotinib was paired with the KRAS inhibitor daraxonrasib.
Notably, in the NCI-H2122 lung cancer model (KRASG12C), which has been described as KRAS inhibitor-insensitive, combination treatment with narmafotinib and adagrasib enhanced tumour responsiveness. This suggests potential utility in tumours that show limited initial response to KRAS inhibition alone.
Additionally, narmafotinib demonstrated activity in patient-derived organoids across multiple KRAS mutation types, including G12V, G12D, G12R, and wild-type KRAS, suggesting broad applicability beyond specific mutations.
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Where narmafotinib stands in clinical development
Narmafotinib is currently being evaluated in the ongoing ACCENT trial, where it is dosed in combination with gemcitabine and Abraxane in first-line patients with advanced pancreatic cancer. Clinical data reported to date includes:
- 35% confirmed objective response rate (19/55 patients), including one complete response and one pathological complete response
- 7.7 months median progression-free survival
- Favourable comparison to the MPACT benchmark study for gemcitabine and Abraxane alone (23% response rate, 5.5 months median PFS)
The combination has been reported as well tolerated with no evidence of increased grade ≥3 adverse events compared to chemotherapy alone. Common narmafotinib-related adverse events included nausea (29.1%), diarrhoea (16.4%), and vomiting (14.5%), with most events being low grade.
A second trial, AMPLICITY, has recently opened at sites in Australia and the United States, investigating narmafotinib in combination with the chemotherapy regimen FOLFIRINOX in advanced pancreatic cancer patients.
Strategic implications for Amplia
The preclinical data presented at the AACR conference positions narmafotinib as a potential combination partner for the numerous KRAS inhibitor programmes currently in clinical development. By targeting FAK signaling, which research suggests becomes hyperactivated following KRAS inhibition and can lead to fibrosis and treatment resistance, narmafotinib addresses a key limitation of KRAS-targeted therapies.
The company’s management has indicated they will be discussing these findings with pharmaceutical and biotechnology companies active in KRAS inhibitor development. Such partnerships could accelerate development timelines and expand the addressable market for narmafotinib beyond its current focus on pancreatic cancer to include lung and ovarian cancers.
Narmafotinib’s profile as a highly potent and selective FAK inhibitor with oral once-daily dosing and reported favourable tolerability in combination with chemotherapy provides a differentiated positioning. The therapy’s activity across multiple KRAS mutation types, rather than being limited to specific genetic variants, broadens its potential patient population and partnership opportunities.
The ongoing ACCENT and AMPLICITY trials will provide further clinical validation of the combination approach, whilst the preclinical KRAS inhibitor data opens potential development pathways in additional tumour types where KRAS mutations are prevalent.
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