AbbVie Gains First Solid Tumor FDA Approval With EMRELIS™ for High c-Met Overexpressing Advanced NSCLC
AbbVie has achieved a key milestone in its oncology pipeline with the announcement that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to EMRELIS™ (telisotuzumab vedotin-tllv). This novel therapy is now approved for adult patients diagnosed with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who exhibit high c-Met protein overexpression (OE) and have previously undergone systemic therapy. The FDA’s decision marks the first and only treatment specifically approved for this subset of NSCLC patients, representing a meaningful step forward in precision oncology.
Defining the Eligible Population: A Biomarker-Driven Approach
EMRELIS targets a distinct NSCLC subpopulation characterized by high c-Met protein overexpression—a condition defined by immunohistochemistry (IHC) as having ≥50% of tumor cells with strong (3+) staining. This molecular profile is detectable via an FDA-approved diagnostic test, specifically the Roche VENTANA® MET (SP44) RxDx Assay, which was approved in parallel with EMRELIS to serve as its companion diagnostic.
The use of a biomarker-guided therapeutic approach reflects the broader trend toward personalized medicine in oncology. While NSCLC accounts for approximately 85% of all lung cancers, not all patients respond the same way to standard treatments due to genetic and proteomic variability within tumors. Roughly 25% of patients with advanced EGFR wild-type, non-squamous NSCLC present with c-Met protein overexpression, and about half of those fall into the high-expression category. This population has historically faced limited treatment options and a generally poor prognosis.
A Novel Antibody-Drug Conjugate With a Unique Mechanism
EMRELIS is classified as a c-Met-directed antibody-drug conjugate (ADC). ADCs represent an innovative therapeutic modality that combines the targeting ability of monoclonal antibodies with the cytotoxic potency of chemotherapy. By homing in on specific tumor biomarkers such as c-Met, ADCs deliver their toxic payload directly to cancer cells, ideally sparing surrounding healthy tissue and improving the therapeutic index.
This mode of action offers a compelling alternative to traditional chemotherapy and checkpoint inhibitors for patients whose tumors express high levels of c-Met but lack other actionable mutations, such as EGFR, ALK, or ROS1. EMRELIS is AbbVie’s first internally developed ADC approved for a solid tumor indication, underlining the company’s strategic emphasis on growing its oncology franchise through innovative platforms.
Regulatory Pathway: Accelerated Approval Backed by LUMINOSITY Study
The FDA granted EMRELIS accelerated approval based on data from the Phase 2 LUMINOSITY trial (NCT03539536), which evaluated the efficacy and safety of telisotuzumab vedotin in patients with advanced NSCLC characterized by c-Met overexpression. In this study, 84 patients with high c-Met protein OE received EMRELIS and achieved an overall response rate (ORR) of 35% (95% confidence interval: 24–46). Furthermore, the median duration of response (DOR) was reported at 7.2 months (95% CI: 4.2–12.0 months), highlighting the clinical activity of the drug in this difficult-to-treat population.
Notably, EMRELIS was granted Breakthrough Therapy Designation (BTD) by the FDA in December 2021, a status designed to expedite development and review for therapies demonstrating substantial improvement over existing options in serious conditions.
The accelerated approval mechanism allows EMRELIS to reach patients more quickly, but it is contingent upon confirmatory evidence from additional trials. To this end, AbbVie is actively conducting the Phase 3 TeliMET NSCLC-01 trial, a global randomized study evaluating EMRELIS as monotherapy in previously treated patients with c-Met overexpressing NSCLC. This study is currently enrolling and is expected to provide the data necessary for potential full approval.
Safety Profile and Tolerability
Like many ADCs, EMRELIS is associated with a specific side effect profile. The most commonly reported adverse reactions (occurring in ≥20% of patients) in the LUMINOSITY trial included peripheral neuropathy, fatigue, decreased appetite, and peripheral edema. While these effects are manageable, clinicians should monitor patients closely during treatment, particularly for signs of neurotoxicity.
In terms of laboratory abnormalities, the most frequently observed Grade 3 or 4 adverse events (≥2%) were decreased lymphocyte counts, hyperglycemia, elevated liver enzymes (ALT and GGT), and electrolyte imbalances including decreased levels of phosphorus, sodium, hemoglobin, and calcium. These findings underscore the importance of routine laboratory surveillance during therapy to mitigate risks and adjust dosing as needed.
Perspectives From Experts and Advocacy Groups
The approval of EMRELIS has been met with optimism by oncologists and patient advocacy organizations alike, who view it as a meaningful addition to the NSCLC treatment landscape.
Dr. Jonathan Goldman, a professor of medicine and director of thoracic oncology clinical trials at UCLA, emphasized the importance of biomarker-based therapies in modern oncology. “We have observed a paradigm shift in oncology in recent decades toward personalized, biomarker-driven therapeutics, allowing for better selection and optimized treatment outcomes,” he said. “People with c-Met overexpressing NSCLC have poor prognosis and limited treatment options, and EMRELIS is a first-in-class ADC that can address a critical unmet need for this patient population.”
Echoing these sentiments, Dr. Upal Basu Roy, Executive Director of Research at the LUNGevity Foundation, noted the urgency for new treatment avenues in lung cancer. “Despite the progress we have seen in the treatment of lung cancer, we need more options for people whose treatments stop working,” said Dr. Roy. “This approval is a welcomed targeted therapy for those with high c-Met protein overexpressing late-stage, non-small cell lung cancer who have seen very limited treatment innovation in the last decade.”
AbbVie’s Strategic Vision for Oncology
For AbbVie, the approval of EMRELIS is more than a regulatory win—it signals the company’s deeper expansion into solid tumors and ADC technology platforms. “EMRELIS, AbbVie’s first internally developed solid tumor medicine and our first solid tumor FDA approval in lung cancer, is a testament to our commitment to develop cancer therapies that aim to improve the course of treatment for patients facing this challenging disease,” said Dr. Roopal Thakkar, Executive Vice President of Research and Development and Chief Scientific Officer at AbbVie.
Dr. Thakkar also highlighted AbbVie’s focus on leveraging advanced technologies and data science to build a robust and diversified pipeline. “We are growing our ADC portfolio designed to deliver the right medicines to the right patients in need across a range of difficult-to-treat tumors.”
With several oncology programs in development and multiple investigational ADCs in clinical trials, AbbVie is clearly positioning itself as a key player in next-generation cancer therapeutics.
The approval of EMRELIS marks a significant step forward in the treatment of advanced NSCLC and sets a precedent for future therapies that exploit tumor-specific biomarkers. For patients with high c-Met protein overexpression who have exhausted standard treatment options, EMRELIS offers a targeted approach backed by promising early clinical data.
While the road to full approval will require confirmatory results from ongoing studies, the accelerated approval of EMRELIS affirms the FDA’s continued support for innovative, precision-based therapies that address urgent unmet needs in oncology.
