Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein Overexpressing, Nonsquamous, EGFR Wild-type Advanced NSCLC: Updated Analysis of the LUMINOSITY Trial

Girard N., Goldman J., Lu S., Bar J., Horinouchi H., Daaboul N., ...Daha Fazla

JTO Clinical and Research Reports, cilt.7, sa.7, 2026 (ESCI, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 7 Sayı: 7
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1016/j.jtocrr.2026.100988
  • Dergi Adı: JTO Clinical and Research Reports
  • Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus
  • Anahtar Kelimeler: Antibody–drug conjugate, Biomarker, c-Met protein, NSCLC, Telisotuzumab vedotin
  • Gazi Üniversitesi Adresli: Evet

Özet

Introduction Telisotuzumab vedotin (Teliso-V) is a c-Met–directed antibody–drug conjugate comprising the monoclonal antibody telisotuzumab and the monomethyl auristatin E payload. Primary analysis of the phase 2 LUMINOSITY trial (NCT03539536) revealed Teliso-V monotherapy 1.9 mg/kg elicited durable responses and had generally manageable safety in patients with locally advanced or metastatic c-Met protein overexpressing, EGFR wild-type, nonsquamous NSCLC. We present updated outcomes with approximately 6 months longer follow-up and explore the impact of previous therapies. Methods Patients (≥18 y; had previous therapy including ≤1 chemotherapy) received 1.9 mg/kg Teliso-V every 2 weeks. c-Met protein overexpression (clinical trial assay for MET [SP44] [Roche]) was defined as greater than or equal to 25% tumor cells with 3+ staining intensity (c-Met high: ≥50% 3+; c-Met intermediate: 25 to <50% 3+). Primary end point was the overall response rate by independent central review per the Response Evaluation Criteria in Solid Tumors version 1.1. Results As of February 21, 2024, 172 patients received at least one dose of Teliso-V; 168 patients (c-Met high, n = 84; c-Met intermediate, n = 84) were evaluable for efficacy. The overall response rate was 29.2% (95% confidence interval [CI]: 22.4–36.7; c-Met high, 34.5% [24.5–45.7]; c-Met intermediate, 23.8% [15.2–34.3]). Median duration of response was 7.2 months (95% CI: 5.5–11.0; c-Met high, 7.2 [95% CI: 4.2–12.0]; c-Met intermediate, 7.2 [95% CI: 4.7–11.5]). Previous therapy (platinum, immune checkpoint inhibitors, or both) did not impact efficacy outcomes. The most common treatment-related adverse event was peripheral sensory neuropathy (any-grade: 31%; grade ≥3: 7%). Conclusions Teliso-V monotherapy 1.9 mg/kg elicited durable responses, irrespective of the type of previous therapy received, and maintained a manageable safety profile in patients with c-Met protein overexpressing EGFR wild-type, nonsquamous NSCLC. ClinicalTrials.gov ID number NCT03539536.