What we commonly refer to as “lung cancer” is in fact many different types of diseases. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases. But it wasn’t until recently that we understood the breadth of molecular subsets that comprise NSCLC, each with unique implications for prognosis and management. Identification of the epidermal growth factor receptor (EGFR) in 2004 marked a pivotal moment in the era of precision medicine for lung cancer.

Breakthroughs like these—large leaps in scientific understanding that deliver profound advances for patient outcomes—inspire our spirit of innovation at Cullinan. In our pursuit of medicines that improve patient lives, we seek to build on these important scientific insights, knowing that despite the progress made, many patients have not been able to benefit from these advances.

A persistent challenge in lung cancer

Among the lung cancer population with EGFR mutations, patients with insertions at exon 20 (ex20ins) represent a significant unmet need segment. These patients often have poorer outcomes compared to those with more common EGFR mutations, such as exon 19 deletions. Ex20ins mutations can be challenging to detect with traditional biomarker testing and frequently convey resistance to approved tyrosine kinase inhibitors (TKIs), unlike mutations in exons 18, 19, and 21, which increase sensitivity to those drugs. After 20 years of advances, treatment options remain limited for those with EGFR ex20ins advanced or metastatic disease, especially for patients who have exhausted available treatment options.

Where do we go from here? The industry must adopt innovative strategies that push the boundaries of scientific progress, accelerate the availability of new treatments, and work across disciplines to deliver medicines that improve the lives of as many patients as possible. As our clinical development strategy at Cullinan Therapeutics advances to later stages, a few key principles guide our approach: creativity paired with discipline, and putting people first. These principles give us the best chance at delivering what we hope will be truly meaningful medicines.

Disciplined science rooted in expertise

The significant unmet need in people with EGFR ex20ins NSCLC gives us a roadmap for what it would take for a medicine to be clinically meaningful. Our urgency to offer patients more options led Cullinan to collaborate with researchers at Taiho Oncology to more fully explore the potential of a novel investigational treatment for EGFR ex20ins mutations in NSCLC.

Complementary expertise enabled our companies to explore creative ways of designing clinical trials. Together, we developed a comprehensive clinical development plan in a variety of treatment settings in EGFR ex20ins NSCLC.

We recently reported positive outcomes from our investigational treatment for patients with ex20ins NSCLC whose disease had progressed despite already receiving prior standard of care treatments such as chemotherapy, amivantamab, and other ex20ins-directed therapies.

This success highlights the potential of our investigational treatment, but what is most meaningful is that an oral therapy that delivers efficacy with a manageable safety profile could represent a significant advance for these patients with heavily pre-treated EGFR ex20ins NSCLC. Buoyed by this progress, we are working swiftly with the goal of making this option broadly available—a testament to our commitment to our mission of bringing new standards of care to more patients.

Hands-on approach driving outcomes

Clinical trial success hinges upon support and simplicity—programs must be scientifically robust yet also practical to implement. A disciplined approach extending across collaborations with others in the clinical development ecosystem helps us leverage external resources while maintaining a lean, efficient internal team.

Success also depends on how we put people first. At Cullinan, we have built a team with expertise in the design and execution of clinical studies who share a commitment to strong collaboration with investigators. We prioritize our accessibility to these critical external collaborators, listening to and adapting to their needs. As a clinician, I know that physicians serve as both interpreters and connectors of patients who are experts in their own disease. ​These invaluable insights are crucial for both the execution of studies and the development of transformational medicines that address patient needs.

Looking ahead

Progress made to date in lung cancer, and hopefully soon for patients living with EGFR exon20ins NSCLC, would not have been possible without the tireless work of the many scientists, investigators, advocates, and patients collectively pursuing a better future.

As an industry, we have the tools to solve the world’s greatest scientific challenges. Our mandate is to remain disciplined and focused, agile, and inventive, so that we may realize these solutions for patients.