Teliso-V Plus Osimertinib Active, Tolerable in TKI-Resistant NSCLC

The ADC received FDA approval for NSCLC with high c-Met overexpression on May 14, 2025.

Telisotuzumab vedotin (Teliso-V; Emrelis) plus osimertinib (Tagrisso) showed clinical activity and was well tolerated in patients with EGFR-mutant non–small cell lung cancer (NSCLC) and c-Met overexpression who had progressed after prior osimertinib, according to results from arm E of a phase 1/1b trial (NCT02099058).¹

After a median follow-up of 7.4 months, the objective response rate (ORR) was 50.0% (95% CI, 33.4%-66.6%) per independent central review (ICR) and 52.6% (95% CI, 35.8%-69.0%) per investigator assessment. All responses were confirmed partial responses. The median duration of response was not reached (NR) per ICR and 8.0 months per investigator assessment. Median progression-free survival (PFS) was 7.4 months (95% CI 5.4-NR) and 6.8 months (95% CI, 5.3-9.2) per ICR and investigator, respectively.

The investigators reported no treatment-emergent adverse events (TEAEs) led to dose-limiting toxicities, although all patients experienced 1 or more TEAE with 37 patients experiencing 1 or more TEAEs possibly related to telisotuzumab vedotin.

Nineteen percent of patients experienced grade 3/4 TEAEs and 11% experienced serious TEAEs. The most frequent any-grade TEAEs were peripheral sensory neuropathy (50%), peripheral edema (32%), nausea (24%), anemia (21%), and fatigue (21%).

TEAEs leading to telisotuzumab vedotin discontinuation, dose interruption, or dose reduction was reported in 9 (24%) patients (6 [16%] possibly related to telisotuzumab vedotin), 22 (58%) patients, and 14 (37%) patients, respectively.

In this patient population, treatment resistance is inevitable, with c-Met protein overexpression leading to resistance to EGFR tyrosine kinase inhibitor (TKI) treatment.

“This combination has the potential to address an unmet medical need in this population,” corresponding author Jonathan Goldman, MD, and colleagues wrote in the study, which appeared in the Annals of Oncology.

Twenty-seven patients discontinued telisotuzumab vedotin, 26 patients discontinued osimertinib, and 25 discontinued the study, mostly due to progressive disease (n = 18/27; 67%).

Study Design

At the data cutoff of March 23, 2023, 41 patients with c-Met protein-overexpressing, EGFR-mutated non-squamous non–small cell lung cancer (NSCLC) received the antibody-drug conjugate telisotuzumab vedotin plus the TKI osimertinib. Teliso-V was evaluated at 1.6 mg/kg in a safety lead-in phase and escalated to 1.9 mg/kg.

In the analysis, 38 patients received telisotuzumab vedotin (1.6 mg/kg, n = 20; 1.9 mg/kg, n = 18, every 2 weeks) plus osimertinib (orally, 80 mg once daily). Dose expansion was included for both doses.

End points included safety and tolerability, pharmacokinetics, ORR, duration of response, and PFS. Treatment continued until disease progression, unacceptable toxicity, or after other discontinuation criteria were met.

In the dose-expansion cohorts, patients had received a maximum of 2 previous lines of therapy, 1 of which must have contained osimertinib, and no more than 1 may have contained chemotherapy.

Patient Demographics and Baseline Characteristics

Sixty-six percent (n = 25) of patients were female, 55% were Asian, and 61% were never smokers. The median age was 60 years (range, 40-79) and 7 patients had central nervous system involvement at baseline. High c-Met protein overexpression was reported in 64% (21 of 33) of patients and intermediate c-Met protein overexpression in 36% (12 of 33) of patients.

Previous Analysis

In an earlier analysis (NCT02099058),² telisotuzumab vedotin had been combined with erlotinib (Tarceva) in 42 patients with c-Met–positive NSCLC. In that study, the most common any-grade AEs reported were neuropathies with 57% of patients experiencing at least 1 event. Median PFS was 5.9 months (95% CI, 2.8-not reached). Patients with EGFR-mutated-positive NSCLC had an ORR of 32.1% and among patients who were c-MET high (n = 15), the ORR was 52.6%.

On May 14, 2025, telisotuzumab vedotin was granted accelerated approval from the FDA for use in NSCLC with high c-Met overexpression based on data from the phase 2 LUMINOSITY trial (NCT03539536).

References

1. Horinouchi H, Cho BC, Camidge DR, et al. Results from a phase Ib study of telisotuzumab vedotin in combination with osimertinib in patients with c-Met protein-overexpressing, EGFR-mutated locally advanced/metastatic non-small-cell lung cancer (NSCLC) after progression on prior osimertinib. Ann Oncol. 2025;36(5):583-591. doi:10.1016/j.annonc.2025.01.001

2. Camidge DR, Barlesi F, Goldman JW, et al. Phase Ib Study of telisotuzumab vedotin in combination with erlotinib in patients with c-Met protein-expressing non-small-cell lung cancer. J Clin Oncol. 2023;41(5):1105-1115. doi:10.1200/JCO.22.00739