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 tumours that overexpress c-Met protein, which may be associated with poor survival.

Dr. Hidehito Horinouchi, of the National Cancer Centre 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% tumour 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 randomised Phase 3 study TeliMET NSCLC-01 (NCT04928846), which is currently enroling.

Source: International Association for the Study of Lung Cancer