Adding Telisotuzumab Vedotin to Osimertinib Shows Activity and Safety in TKI-Resistant NSCLC
Telisotuzumab vedotin plus osimertinib demonstrated safety and efficacy in patients with c-MET protein overexpression.
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Results from an analysis of arm E of the phase 1/1b trial (NCT02099058) evaluating telisotuzumab vedotin (Teliso-V) plus osimertinib (Tagrisso) demonstrated that the combination was effective and tolerable in patients who had progressed after receiving osimertinib.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 Teliso-V.
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 Teliso-V discontinuation, dose interruption, or dose reduction was reported in 9 (24%) patients (6 [16%] possibly related to Teliso-V), 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 Teliso-V, 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 Teliso-V 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 Teliso-V (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 Teliso-V 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%.
