Peripheral Neuropathy Treatable With Teliso-V in C–Met-High NSCLC

The safety profile of the antibody-drug conjugate telisotuzumab vedotin-tllv (Teliso-V; Emrelis) when used to treat c-Met overexpressing non-small cell lung cancer (NCSLC) is largely manageable, according to Jonathan Goldman, MD, the study author presenting data from the phase 2 LUMINOSITY trial (NCT03539536) at the 2025 American Society of Clinical Oncology Annual Meeting.

Data from LUMINOSITY led to the antibody-drug conjugate’s accelerated approval for c-Met overexpressing NSCLC in May 2025.¹ Findings from LUMINOSITY made available at the conference demonstrated durable response in NSCLC with c-Met overexpression regardless of whether patients received prior platinum-based chemotherapy or immune checkpoint inhibitors.²

Goldman, professor of medicine at the David Geffen School of Medicine at University of California, Los Angeles, explained that peripheral neuropathy and ocular toxicities were among the most common adverse events reported in LUMINOSITY.

According to his study abstract, the most frequently reported treatment-related adverse events were peripheral sensory neuropathy, peripheral edema, and fatigue, reported in 31%, 16%, and 14% of patients, respectively.

Transcript

MET is a target that is really quite prevalent. In lung cancer when we’re talking about targeted therapies, often we’re talking about 10% or even 1% to 5%. MET overexpression is much more common. Even if you look at the really high degree of MET expression, you’re looking at 12% or 25% depending on how you identify it, and that is quite prevalent at initial diagnosis, but also becomes more prevalent as tumors become resistant to first-line therapy. There, we see an increase of about 10% in positivity on testing.

Telisotuzumab vedotin is an antibody-drug conjugate. The antibody is targeting an extracellular epitope of MET. Attached to the antibody is the toxic payload. C-Met overexpression is the most important specific issue regarding Teliso-V usage. C-Met expression was able to identify the patients [who] were most likely to get a significant benefit and the ones [who] have the initial approval. That’s c-Met 3+ at 50% or greater of cells. In that setting, it’s a very appealing choice for patients. [There were] no reported differences in toxicity at this point based on c-Met expressions.

The antibody-drug conjugates are giving us a new set of toxicities to be aware of. With an MMAE payload, we have 2 primary ones. One is ocular toxicities, and those have been relatively rare and relatively mild with Teliso-V. Eye wetting drops and sometimes an ophthalmology evaluation [may be needed], but [ocular toxicities are] rarely high grade and [are] reversible and rarely significantly problematic.

We also do see peripheral neuropathy—any-grade peripheral neuropathy in about 30%, and about 10% have higher-grade peripheral neuropathy, as opposed to taxane neuropathy. I have found [peripheral neuropathy] to be reversible, though, so that is very reassuring to me and the patients.

We sometimes need to take a treatment break or dose reduce when we restart. The other thing about the neuropathy is that it is cumulative. Patients [who] have been on treatment for 3, 4, or 8 months and derive benefit do get some neuropathy and require attention for it. But I found it to be manageable, and certainly, if you compare it with docetaxel, which also has neuropathy, it is not as treatment-limiting as it is with docetaxel.

This transcript has been edited for clarity and conciseness.

Reference

1. U.S. FDA approves EMRELIS (telisotuzumab vedotin-tllv) for adults with previously treated advanced non-small cell lung cancer (NSCLC) with high c-Met protein overexpression. News release. AbbVie. May 14, 2025. Accessed May 14, 2025. https://news.abbvie.com/2025-05-14-U-S-FDA-Approves-EMRELIS-TM-telisotuzumab-vedotin-tllv-for-Adults-With-Previously-Treated-Advanced-Non-Small-Cell-Lung-Cancer-NSCLC-With-High-c-Met-Protein-Overexpression
2. Goldman J, Lu S, Bar J, et al. LUMINOSITY, a phase 2 study of telisotuzumab vedotin in patients with c-Met protein–overexpressing non-squamous EGFR-wildtype advanced NSCLC: efficacy outcomes by prior therapy. J Clin Oncol. 2025;43(suppl 16):8618. doi:10.1200/JCO.2025.43.16_suppl8618