A new subgroup analysis of the phase II LUMINOSITY trial demonstrated similar benefits for Asian patients compared to those observed in global populations with non-squamous EGFR wild-type non-small cell lung cancer (NSCLC) exhibiting c-MET overexpression.
The open-label trial evaluated telisotuzumab vedotin (Teliso-V), an antibody-drug conjugate designed to target the c-MET protein and deliver a cytotoxic payload of monomethyl auristatin E (MMAE). Approximately 25% of non-squamous, EGFR wild-type NSCLC overexpresses the c-MET protein, and this overexpression is linked to poorer clinical outcomes.
“Treatment with Teliso-V resulted in a compelling and durable response, particularly in the population with high c-Met expression,” said Hidehito Horinouchi, MD, PhD, Professor of Thoracic Oncology and Assistant Chief at the National Cancer Center Hospital in Tokyo. “The sub-group results are comparable to those observed in the overall patient population.”
Dr. Horinouchi presented data from LUMINOSITY on the effects of Teliso-V in a subgroup of patients of Asian descent who had advanced or metastatic non-squamous NSCLC with c-Met overexpression and wild-type EGFR during the session titled Transforming Cancer Therapy: Biomarkers and Novel ADCs at the 2024 World Conference on Lung Cancer.
The LUMINOSITY study reported an overall response rate (ORR) of 29% among patients with c-Met overexpression. Specifically, the ORR was 35% for patients with high c-Met expression and 23% for those with intermediate c-Met expression. The subgroup analysis of Asian patients—comprising 57 out of 172 patients—revealed a 35% ORR, with 46% of patients exhibiting high c-Met expression and 23% of those with intermediate c-Met expression responding.
“This is quite similar to the overall population,” Prof. Horinouchi said. “The progression-free survival rate is similar between c-Met high and c-Met intermediate (6 months).”
And, when compared to 17 months for c-Met intermediate responders, there is a better trend in overall survival for the c-Met high response patients at 25 months, he said.
All participants had received one or two prior lines of systemic therapy in the advanced or intermediate setting. The primary endpoint was the overall response rate (ORR), while secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).
The median age of the global cohort was 65 years. The majority of participants (59%) were male, and 30% identified as Asian. Just over 20% had brain metastases at baseline, and c-Met status was roughly even with 48% classified as high and 52% as intermediate.
The median DOR for the overall patient population was 8 months, with 9 months for patients with high c-Met expression and 7 months for those with intermediate c-Met expression. Just over half of the patients (57%) experienced a median DOR of at least 6 months, including 65% of patients with high c-Met expression and 47% of patients with intermediate c-Met expression.
Most patients (81%) experienced treatment-related adverse events (TRAEs), with the most common being peripheral sensory neuropathy (30%), peripheral edema (16%), and fatigue (14%). About one-quarter of patients (28%) experienced TRAEs classified as grade 3 or higher, with peripheral sensory neuropathy being the most prevalent at 7%.
Patient demographics and characteristics were comparable in the Asian cohort, which had a median age of 65 years, with 71% of participants being male and 14% having brain metastases. A slightly higher percentage of Asian patients (54%) exhibited high c-Met levels, while 46% had intermediate c-Met levels.
The median duration of treatment was 5 months and disease progression was the most common reason for discontinuation of the study drug, accounting for 49% of cases, followed by adverse events at 25%.
The DCR in the Asian cohort was 67%, with 69% for c-Met high and 64% for c-Met intermediate. The median DOR was 7 months, with 7 months for c-Met high and 8 months for c-Met intermediate. Less than half of the Asian patients (47%) experienced a DOR of at least 6 months, with 50% for c-Met high and 40% for c-Met intermediate. All confirmed responses were partial.
TRAEs were similarly reported, with 90% of patients experiencing at least one TRAE. The most prevalent TRAE was peripheral sensory neuropathy, occurring in 21% of patients.
Enrollment continues in the ongoing global, randomized phase III study comparing Teliso-V to docetaxel.
