image: Dr. Hidehito Horinouchi, of the National Cancer Center Hospital in Japan
Credit: Dr. Hidehito Horinouchi, of the National Cancer Center Hospital in Japan
LUMINOSITY Trial Demonstrates Telisotuzumab Vedotin Shows Durable Response in Asian Patients with c-Met Protein-Overexpressing EGFR WT Nonsquamous NSCLC
(San Diego, Calif.--September 10, 2024 10:35 a.m.) -- The c-Met-directed antibody-drug conjugate telisotuzumab vedotin demonstrated durable responses and an acceptable safety profile in patients of Asian race with c-Met protein-overexpressing, epidermal growth factor receptor (EGFR) wildtype (WT), locally advanced/metastatic nonsquamous non-small cell lung cancer (NSCLC), according to research presented today at the International Association for the Study of Lung Cancer’s 2024 World Conference on Lung Cancer.
The c-Met protein is a receptor tyrosine kinase that mediates cell proliferation, survival, and angiogenesis, and can be dysregulated in patients with NSCLC. Approximately 25% of patients with EGFR WT nonsquamous NSCLC have tumors that overexpress c-Met protein, which may be associated with poor survival.
Dr. Hidehito Horinouchi, of the National Cancer Center Hospital in Japan, participated in the LUMINOSITY phase 2 (NCT03539536) clinical trial aiming to identify the c-Met protein-overexpressing NSCLC population best suited to Teliso-V monotherapy and expand selected groups for further evaluation.
For the purposes of this study, the researchers defined c-Met protein overexpression as greater than 25% tumor cells with more than 3+ staining (high: ≥50% 3+; intermediate [int]: 25% to <50% 3+). Patients received 1.9 mg/kg intravenously every two weeks and the primary endpoint was Overall Response Rate (ORR).
In total, 172 patients with c-Met protein-OE EGFR WT nonsquamous NSCLC received at least one dose of Teliso-V, 57 of whom were Asian. A total of 48 Asian patients (c-Met high, n=26; c-Met intermediate, n=22) were evaluable for efficacy.
Median age in patients of Asian race was 65 years (range 47-82), 71% were male, and 67% had ECOG PS ≥1. Overall, 92% received prior platinum therapy and 77% had prior immune checkpoint inhibitor therapy. For the Asian population, the ORR was 46.2% (c-Met high), 22.7% (c-Met intermediate), and 35.4% (overall). Median duration of response was 6.9 months (c-Met high), 8.3 months (c-Met intermediate), and 6.9 months (overall). The most common adverse events were hypoalbuminemia (32%), peripheral sensory neuropathy (23%), and pneumonia (21%).
“Compelling and durable responses were observed in patients of Asian race with c-Met protein-OE nonsquamous EGFR WT NSCLC, especially in patients with c-Met high; these results are similar to the overall population,“ according to Dr. Horinouchi. He added that Teliso-V had an acceptable safety profile that was clinically manageable.
Teliso-V is being evaluated as a monotherapy in patients with previously treated c-Met overexpressing EGFR wild type nonsquamous NSCLC in the randomized Phase 3 study TeliMET NSCLC-01 (NCT04928846), which is currently enrolling.
About the IASLC:
The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated solely to the study of lung cancer and other thoracic malignancies. Founded in 1974, the association's membership includes more than 10,000 lung cancer specialists across all disciplines in over 100 countries, forming a global network working together to conquer lung and thoracic cancers worldwide. The association also publishes the Journal of Thoracic Oncology, the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies. Visit www.iaslc.org for more information.
About the WCLC:
The World Conference on Lung Cancer (WCLC) is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies, attracting nearly 7,000 researchers, physicians and specialists from more than 100 countries. The goal is to increase awareness, collaboration and understanding of lung cancer, and to help participants implement the latest developments across the globe. The conference will cover a wide range of disciplines and unveil several research studies and clinical trial results. For more information, visit https://wclc2024.iaslc.org.
About Telisotuzumab-Vedotin (Teliso-V)
Teliso-V is an investigational first-in-class, c-Met protein directed antibody-drug conjugate (ADC) targeting patients with c-Met overexpressing tumors. c-Met is a receptor tyrosine kinase that is overexpressed in many solid tumors including NSCLC. Teliso-V is being evaluated as a monotherapy in patients with previously treated c-Met overexpressing EGFR wild type non squamous NSCLC in the randomized Phase 3 study TeliMET NSCLC-01, which is currently enrolling. Further information on clinical trials for Teliso-V is available at https://clinicaltrials.gov/. Currently there are no approved cancer therapies specifically for patients with c-Met overexpressing NSCLC. Teliso-V is not approved by any regulatory authority and its safety and efficacy have not been established.
About the LUMINOSITY trial
The LUMINOSITY trial (M14-239), is an ongoing Phase 2 study designed to identify the target NSCLC populations that overexpress c-Met best suited for Teliso-V monotherapy in the second line or third line setting, and then to expand the groups to further evaluate efficacy in the selected populations. The endpoints include overall response rate (ORR), duration of response (DoR), disease control rate (DCR) and progression-free survival (PFS) per independent central review (ICR) as well as overall survival (OS).