Amplia Therapeutics has partnered with Eli Lilly and Company to evaluate its investigational FAK inhibitor narmafotinib alongside Lilly’s next-generation KRAS G12C inhibitor olomorasib in a phase 1b/2b clinical trial for advanced non-small cell lung cancer, targeting a major drug resistance mechanism in a global market.
A new clinical trial agreement aims to tackle one of the most stubborn hurdles in targeted lung cancer treatment: why tumors eventually outsmart modern inhibitors. Amplia Therapeutics has executed a Clinical Trial Collaboration and Supply Agreement with Eli Lilly and Company to test the combination of its investigational Focal Adhesion Kinase inhibitor, narmafotinib, alongside Lilly’s next-generation KRAS G12C inhibitor, olomorasib, as a second-line treatment for advanced non-small cell lung cancer.
Clinical Trial Launch and Trial Sites
Under the terms of the agreement, Amplia will sponsor and conduct the clinical trial, which is planned to begin in late 2026 across trial sites in Australia and the United States. Prior to executing the contract, both companies worked together to draft an advanced clinical study protocol and will now finalize study documents.
The trial’s design reflects a broader strategic expansion for Amplia, moving the clinical development footprint of narmafotinib beyond pancreatic and ovarian cancers into the NSCLC market. KRAS G12C mutations themselves occur in roughly 13% of NSCLC patients and in 1% to 3% of patients with other solid tumors.
“This collaboration is an exciting new stage in the clinical progression of narmafotinib. We and others have shown that the combination of FAK and KRAS inhibition can lead to improved outcomes, and we are excited to advance with this clinical study to explore the combination potential with olomorasib, Lilly’s leading KRAS G12C inhibitor currently undergoing two global Phase 3 studies in NSCLC.”
Dr Chris Burns, Amplia CEO and Managing Director
Scientific Rationale: Overcoming Resistance via Focal Adhesion Kinase
While approved targeted therapies like sotorasib and adagrasib have changed the treatment landscape for KRAS G12C-mutant lung cancer, their clinical benefit as single agents often remains short-lived. Most patients eventually develop resistance.
Research indicates that FAK activation is a key driver of resistance to KRAS G12C inhibitors. By pairing olomorasib with narmafotinib, the trial hopes to suppress these underlying resistance pathways.
The partnership builds on safety and efficacy data from Amplia’s ACCENT study, which demonstrated that narmafotinib carries no significant tolerability burden beyond chemotherapy alone while delivering encouraging efficacy signals. Lilly’s in-kind supply of olomorasib allows Amplia to pursue this expansion efficiently in a high-value indication.
Unmet Needs in KRAS-Mutant Lung Cancer
Beyond the G12C mutation subgroup, the broader lung cancer field faces persistent therapeutic gaps. Benjamin Herzberg, MD, of the Division of Hematology/Oncology at Columbia University Irving Medical Center, noted that the clearest gap in the field is the complete absence of approved targeted therapies for any KRAS mutation outside of G12C. KRAS G12D accounts for approximately 15% of KRAS-mutant NSCLC and roughly 5% of all NSCLC cases—a prevalence comparable to MET exon 14 skipping mutations or EGFR exon 20 insertions—yet lacks an approved inhibitor.
Emerging agents are beginning to target these non-G12C populations. For instance, a phase 1 trial evaluating the first-in-class KRAS G12D-targeted protein degrader setidegrasib (ASP3082) at a recommended phase 2 dose of 600 mg weekly enrolled 45 patients with previously treated KRAS G12D-mutant NSCLC, yielding a partial response rate of 36% (95% CI, 22%-51%), a median progression-free survival of 8.3 months, and an estimated 12-month overall survival of 59%.
Herzberg added that because many G12C-mutant patients have a smoking history, immunotherapy continues to anchor frontline management since it offers the best chance for long-term disease control. Clinical investigation is also testing next-generation G12C inhibitors combined directly with checkpoint inhibitors. Data from the LOXO-RAS-20001 trial evaluating olomorasib alongside pembrolizumab showed an objective response rate of 73.9% in first-line patients, a combination currently being evaluated against chemoimmunotherapy in the registrational SUNRAY-01 trial.
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