by International Association for the Study of Lung Cancer

Credit: Pixabay/CC0 Public Domain

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 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 II (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.

The 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," said 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 III study TeliMET NSCLC-01 (NCT04928846), which is currently enrolling.

Provided by International Association for the Study of Lung Cancer