Dr Nicolas Girard on LUMINOSITY: Teliso-V Improves PROs in NSCLC

Nicolas Girard, MD, professor of respiratory medicine at Versailles Saint Quentin University, head of the Curie-Montsouris Thorax Institute, and chair of the Medical Oncology Department at Institut Curie, discusses patient-reported outcomes (PROs) in the phase 2 LUMINOSITY trial (NCT03539536) of telisotuzumab vedotin (Teliso-V) in c-Met protein overexpressing, EGFR wild-type, nonsquamous non-small cell lung cancer (NSCLC).

In the primary analysis of the LUMINOSITY trial, Teliso-V, an investigational antibody-drug conjugate (ADC), demonstrated promising and durable responses along with a manageable safety profile in patients with c-Met–overexpressing, EGFR wild-type, nonsquamous NSCLC.¹ An analysis of PROs in the trial, presented by Girard at the European Society for Medical Oncology Congress 2024, showed improvements in quality of life (QOL) with Teliso-V in addition to the positive clinical outcomes seen in the study.²

Transcript

How was QOL measured in the LUMINOSITY trial, and what symptoms or QOL factors were most improved by Teliso-V treatment?

Well, Teliso-V is an ADC targeting c-Met. It was assessed in the LUMINOSITY trial in multiple cohorts of patients with c-Met–overexpressing non–small cell lung cancer. And finally, the expansion was conducted in nonsquamous cell carcinomas, EGFR wild-type. So this is a patient population that will be enrolled in the phase 3 trial comparing Teliso-V to docetaxel—the TeliMET trial.

In LUMINOSITY, we see a pretty high response rate of 29% of patients, even higher in c-Met–high patients, 35% response rate; median PFS [progression-free survival] of 6 months; and median overall survival of 14 months. So, very interesting to see that the patient-reported outcomes actually follow the efficacy and safety data from LUMINOSITY. We see an improvement in the key cancer-related symptoms of cough and chest pain—an improvement in these symptoms as reported by the patient, and that was even higher in c-Met–high patients. So this is perfectly in line with the response rates that are reported in this study.

We see that quality of life, physical functioning, and all other symptoms are maintained. And this is also in line with what we have for the time to degradation of quality of life. We see that this time is more prolonged in patients who are responders, and this is pretty expected—in all studies you have that. But here we also have a more prolonged time to deterioration in patients with disease control, meaning including the patients with stable disease. So for the patients, it's not only a matter of response, it's also a matter of stable disease, with a clear benefit in terms of quality of life to achieve in the second-line setting stable disease.

What we see, finally, is that patients are reporting about the side effects, for example, peripheral neuropathy, we see a deterioration as reported by the patients, and this is in line with a high frequency of peripheral neuropathy occurring in 40% of the patients—10% grade 3 or higher side effects—and this is obviously something to monitor and proactively manage, especially for the subsequent trials, including the TeliMET trial.

For responders, how do the improvements in QOL compare with historical data on other treatments for nonsquamous NSCLC?

Well, that's a very good question. Clearly, the response rate of 29% is higher than what was prespecified in LUMINOSITY, so this is a positive trial. It's also higher than what we have with docetaxel, with response rate maximums of 15% to 17%, so this is the rationale to go further into the phase 3. TeliMET is randomizing patients between Teliso-V and docetaxel. The expectation is that we will have a higher efficacy, but also a better safety profile, because docetaxel is obviously associated with frequent treatment-related adverse events.

Can you speak to the overall importance of examining patient-reported outcomes data in lung cancer clinical trials?

That's a very important point, especially in single-arm, phase 2 studies, because in the end, it reflects not only safety, but also efficacy. So it's a global view of the actual benefit and, from a patient perspective, for the value of a drug. And I know that the health care authorities are looking more and more at integrating patient-reported outcomes in the assessment, which is good, because at the end, it's not only a matter of response, not only a matter of survival, it's how is the quality of the survival, and whether we have a high burden or not with these new compounds.

References

1. Camidge DR, Bar J, Horinouchi H, et al. Telisotuzumab vedotin monotherapy in patients with previously treated c-Met protein–overexpressing advanced nonsquamous EGFR-wildtype non–small cell lung cancer in the phase II LUMINOSITY trial. J Clin Oncol. Published online June 6, 2024. doi:10.1200/JCO.24.00720

2. Girard N, Lu S, Bar J, et al. Patient-reported outcomes (PROs) in the LUMINOSITY trial: evaluating telisotuzumab vedotin (Teliso-V) in patients (pts) with c-Met protein overexpressing (OE), EGFR wildtype, non-squamous non-small cell lung cancer (NSQ NSCLC). Presented at: European Society of Medical Oncology Congress 2024; September 13-17, 2024; Barcelona, Spain. Poster 1313P.