The Phase 2 LUMINOSITY trial (NCT03539536) evaluating telisotuzumab vedotin (Teliso-V) in patients with c-Met protein-overexpressing, EGFR wild-type, nonsquamous non-small cell lung cancer (NSCLC) has demonstrated promising improvements in patient-reported outcomes (PROs), alongside previously reported clinical benefits. These findings, presented at the European Society for Medical Oncology (ESMO) Congress 2024, suggest that Teliso-V not only offers durable responses but also enhances the quality of life for this patient population.
LUMINOSITY Trial: Efficacy and Patient Experience
Teliso-V, an investigational antibody-drug conjugate (ADC) targeting c-Met, was assessed in the LUMINOSITY trial across multiple cohorts of patients with c-Met-overexpressing NSCLC. The expansion cohort focused on nonsquamous cell carcinomas with EGFR wild-type, mirroring the patient population slated for the Phase 3 TeliMET trial, which compares Teliso-V to docetaxel. The LUMINOSITY trial reported a 29% response rate, which climbed to 35% in patients with high c-Met expression. The median progression-free survival (PFS) was 6 months, and the median overall survival (OS) reached 14 months.
Impact on Quality of Life
According to Dr. Nicolas Girard, professor of respiratory medicine at Versailles Saint Quentin University, the patient-reported outcomes aligned with the efficacy and safety data from LUMINOSITY. Patients reported improvements in key cancer-related symptoms such as cough and chest pain, with even more pronounced benefits observed in the c-Met-high subgroup. Furthermore, the study indicated that quality of life and physical functioning were maintained throughout the treatment period. Time to degradation of quality of life was prolonged in responders and in patients who achieved stable disease.
Tolerability and Adverse Events
While the LUMINOSITY trial highlighted the benefits of Teliso-V, it also shed light on potential side effects. Peripheral neuropathy was reported by patients, correlating with the observed 40% incidence rate (10% grade 3 or higher). This underscores the importance of proactive monitoring and management of this adverse event in future trials, including the TeliMET trial.
Teliso-V vs. Docetaxel
With a response rate of 29%, Teliso-V outperformed the prespecified threshold in the LUMINOSITY trial and exceeded the typical response rates of 15% to 17% seen with docetaxel. This provides the rationale for the ongoing Phase 3 TeliMET trial, which randomizes patients to receive either Teliso-V or docetaxel. The expectation is that Teliso-V will demonstrate superior efficacy and a more favorable safety profile compared to docetaxel, which is often associated with significant treatment-related adverse events.
The Importance of Patient-Reported Outcomes
Patient-reported outcomes are increasingly recognized as critical endpoints in cancer clinical trials, particularly in single-arm, Phase 2 studies. They provide a comprehensive view of a drug's value from the patient's perspective, encompassing both safety and efficacy. As healthcare authorities place greater emphasis on integrating PROs into their assessments, the focus shifts beyond mere response rates and survival to encompass the overall quality of survival and the burden associated with new treatments.
