Amplia and Lilly Partner to Advance Narmafotinib Plus Olomorasib for KRAS G12C-Mutant NSCLC

Amplia Therapeutics has signed a Clinical Trial Collaboration and Supply Agreement (CTCSA) with Eli Lilly and Company to investigate the combination of investigational FAK inhibitor narmafotinib and Lilly’s next-generation KRAS G12C inhibitor olomorasib in patients with advanced KRAS G12C-mutant NSCLC. The multinational Phase 1b/2b trial is scheduled to begin in late 2026 across sites in Australia and the United States, marking Amplia’s expansion beyond pancreatic and ovarian cancer into lung cancer.

Scientific and Clinical Context

KRAS G12C mutations occur in approximately 13% of NSCLC cases and in 1% to 3% of other solid tumors. Although currently approved KRAS G12C inhibitors have improved treatment options after prior therapy, many patients experience only modest responses before developing acquired resistance within months.

Amplia’s strategy targets one of the major biological drivers of this resistance. Narmafotinib inhibits focal adhesion kinase (FAK), a signaling protein increasingly recognized as a key mediator of adaptive resistance to KRAS inhibition. Preclinical and translational studies suggest that FAK activation promotes tumor survival through multiple mechanisms, including FAK-YAP signaling, fibrogenesis, and remodeling of the tumor microenvironment. Combining FAK inhibition with KRAS blockade may therefore extend and deepen clinical responses.

Phase 1b/2b Trial to Evaluate Safety and Efficacy

The upcoming Phase 1b/2b study will evaluate the safety and efficacy of narmafotinib plus olomorasib as a second-line treatment for patients with advanced NSCLC harboring KRAS G12C mutations. Amplia will lead trial execution, while Lilly will supply olomorasib and collaborate on finalizing the clinical protocol and study documentation.

Olomorasib is Lilly’s late-stage, highly selective next-generation KRAS G12C inhibitor and is currently being evaluated in two global Phase 3 registrational studies (NCT06890598). The collaboration builds on encouraging evidence supporting the combination of FAK and KRAS inhibition and provides an opportunity to assess whether this approach can delay or overcome treatment resistance.

The agreement also broadens Amplia’s oncology development strategy. NSCLC represents an estimated US$31 billion global market that is projected to exceed US$60 billion by 2033, substantially expanding the potential clinical and commercial reach of narmafotinib.

Executive Perspective

Amplia Chief Executive Officer and Managing Director Dr. Chris Burns said the collaboration represents an important milestone in the development of narmafotinib. He noted that both Amplia and independent researchers have generated evidence supporting the combination of FAK and KRAS inhibition and expressed confidence that evaluating narmafotinib alongside olomorasib could further improve outcomes for patients with KRAS G12C-mutant NSCLC.

Future Development

The new collaboration extends narmafotinib’s clinical development into a major oncology indication while strengthening Amplia’s position as a developer of combination therapies targeting resistance mechanisms in solid tumors. Trial initiation is expected in late 2026 following completion of the clinical protocol, with patient enrollment planned across Australia and the United States.

Beyond NSCLC, Amplia continues to evaluate narmafotinib in the ACCENT and AMPLICITY pancreatic cancer studies, while recruitment for the PRROSE ovarian cancer trial is expected to begin later this year, further expanding the investigational FAK inhibitor’s clinical development program.

 Reference

AMPLIA SIGNS COLLABORATION AGREEMENT WITH LILLY, EVALUATING NARMAFOTINIB PLUS LILLY’S KRAS G12C INHIBITOR, OLOMORASIB, IN NON-SMALL CELL LUNG CANCER