A New Door in Lung Cancer: Targeting MET Amplification as a Primary Driver
Expert Perspectives · Keira Smith · 2026-06-10
Following the 2026 ASCO Annual Meeting, Christian Rolfo, MD, PhD, Director of the Division of Medical Oncology and a Thoracic Oncology Specialist at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, sat down with Waqas Haque, MD, MPH, to discuss the evolving role of MET amplification in stage IV recurrent non-small cell lung cancer (NSCLC) and the rationale behind a phase 2 study of subcutaneous amivantamab. Their discussion highlighted an important unmet need in lung cancer care: while MET amplification is recognized in clinical practice, there is still no established standard targeted therapy specifically for these patients.
Understanding MET Amplification
Dr. Rolfo emphasized that the MET pathway is complex and clinically significant because it can be altered in several different ways. “MET is a very interesting pathway,” he said, noting that clinicians already have approved tyrosine kinase inhibitors for MET exon 14 skipping mutations and are also exploring MET overexpression in ongoing drug development.
Historically, however, MET amplification has been viewed primarily as a mechanism of resistance to therapies such as EGFR- and ALK-directed treatment. That framing may now be changing.
Dr. Rolfo explained, “We were thinking, why are we not targeting MET amplification as a primary driver?” He noted that earlier estimates placed MET amplification in about 3% to 4% of lung tumors, while a recently published analysis of more than 82,000 lung cancer cases found a prevalence of approximately 2.9%. Even at that rate, the population is clinically meaningful and has lacked a dedicated therapeutic approach.
The Unmet Need in Treatment
For patients with MET-amplified NSCLC, current treatment remains largely nonspecific. Dr. Rolfo said, “Unfortunately, we don’t have a specific drug for MET amplification.” As a result, these patients typically receive standard first-line therapy, including chemotherapy with immunotherapy or, in select cases, PD-L1–directed monotherapy. In the second-line setting, options remain limited, underscoring the importance of new studies.
The trial also reflects a broader effort to improve patient identification. Dr. Rolfo pointed out that lung cancer testing is still not universal across histologies and that squamous and non-squamous tumors may both harbor clinically relevant MET amplification. “It’s important that we include them,” he said, explaining why the study was designed with separate squamous and non-squamous cohorts.
Why Subcutaneous Amivantamab Matters
Beyond activity, the subcutaneous formulation may offer a practical advantage for patients. Dr. Rolfo said one of its biggest benefits is the lack of this infusion reaction toxicity that was common with intravenous administration. He added that although injection-site reactions can occur, the subcutaneous approach is generally better tolerated and far less time-consuming. “It’s not time-consuming for patients to be in the hospital for a period for observation,” he said.
Looking Ahead
If the study meets its response endpoint, Dr. Rolfo believes the treatment could eventually find a place in the second-line setting, particularly as an alternative to more toxic chemotherapy. “Everybody wants to run away from docetaxel for the toxicity,” he said. Still, he stressed the need for caution and further evidence before changing practice. For now, the study represents what he called “an opportunity for our patients” and a chance to validate a difficult but promising target.
Key Takeaways
MET amplification may be more than a resistance mechanism; it could serve as a primary oncogenic driver in a subset of NSCLC.
Prevalence appears to be about 2.9% based on a large recent analysis.
There is currently no standard targeted therapy specifically for MET-amplified NSCLC.
The phase 2 study of subcutaneous amivantamab aims to address this unmet need.
The subcutaneous formulation may improve tolerability and convenience by reducing infusion-related reactions and chair time.
About the Speakers
Christian Rolfo, MD, PhD, is the Director of the Division of Medical Oncology at The Ohio State University Comprehensive Cancer Center. He specializes in the treatment of patients with lung cancer, mesothelioma, and other thoracic malignancies. Dr. Rolfo also serves as Associate Director for Early-Phase Clinical Trials and conducts research in new therapeutics for thoracic cancers.
Waqas Haque, MD, MPH, is a second-year Hematology/Oncology Fellow at the University of Chicago. He recently completed his Internal Medicine Residency at New York University (NYU) in a Clinical Investigator Track. Dr. Haque has balanced his patient care work with a variety of research projects. During his fellowship training at the University of Chicago, he plans to further his work in innovative clinical trial design, value-based care delivery to cancer patients, and clinical investigation.