Emrelis (telisotuzumab vedotin-tllv)

These data suggest that c-Met protein OE is associated with MET mRNA expression, shows limited overlap with other MET aberrations, and may be linked to poor prognosis in NSCLC.

P2, N=270, Active, not recruiting, AbbVie | Trial primary completion date: Oct 2025 --> Jul 2026

Moreover, the combination with epidermal growth factor receptor inhibitors like Osimertinib and Erlotinib enhances outcomes, but the combination with immunotherapy (Nivolumab) provided negligible benefit. Teliso-V is highly effective in MET-high NSCLC with tolerable side effects. Its combination with AI holds the hope of early diagnosis, individualized treatment, and intelligent ADCs of the future, but for this to manifest, clinical data and biomarker improvements must materialize.

DDI magnitude was comparable to that observed between another approved ADC with the same MMAE payload (brentuximab vedotin) and ketoconazole and rifampin. The current PBPK simulations demonstrated a lack of perpetrator effect of Teliso-V on midazolam, a sensitive CYP3A substrate. The current analysis provides important information on Teliso-V DDI potential and further demonstrates the utility of PBPK models, particularly in oncology, where dedicated DDI studies are challenging.

P2, N=270, Active, not recruiting, AbbVie | Trial primary completion date: Jul 2026 --> Oct 2025

P1, N=237, Active, not recruiting, AbbVie | Trial completion date: Nov 2025 --> Aug 2026 | Trial primary completion date: Nov 2025 --> Aug 2026

P2, N=270, Active, not recruiting, AbbVie | Trial completion date: Oct 2025 --> Aug 2026 | Trial primary completion date: Oct 2025 --> Jul 2026

In this context, the bispecific EGFR/MET antibody amivantamab has demonstrated encouraging efficacy, regardless of MET alterations. Furthermore, the combination of the ADC telisotuzumab vedotin and osimertinib has been associated with activity in EGFR-mutant, c-MET protein-overexpressing, osimertinib-resistant NSCLC...The success of these targeted approaches relies on tissue re-biopsy at progression and accurate molecular profiling. Yet, tumor heterogeneity and procedural limitations may challenge the feasibility of re-biopsy, making biomarker-agnostic strategies viable alternatives.

On 14 May 2025, telisotuzumab vedotin received accelerated approval in the USA for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) with high c-Met protein overexpression, as determined by an FDA-approved test, who have received a prior systemic therapy. This article summarizes the milestones in the development of telisotuzumab vedotin leading to this first approval for NSCLC.

To date, the MET tyrosine-kinase inhibitors (TKIs) capmatinib, tepotinib and savolitinib have been approved for the treatment of advanced-stage METex14-mutant NSCLC...Indeed, in May 2025, the MET-directed ADC telisotuzumab vedotin was approved by the FDA for patients with previously treated advanced-stage nonsquamous NSCLC overexpressing MET (≥50% of tumour cells with 3+ staining on immunohistochemistry). Understanding the unique MET-related adverse events will be crucial when incorporating these agents into daily clinical practice. In this Review, we highlight the rationale for targeting MET alterations across various solid tumour types and provide a summary of the clinical efficacy and toxicity profiles of the approved and emerging MET-targeted TKIs, monoclonal or bispecific antibodies and ADCs.

This review summarizes the frequency of MET alterations across different cancer types and the clinical validation of MET alterations in MET-targeted therapies, offering a detailed comparison of objective response rates (ORR) for therapies including crizotinib, capmatinib, tepotinib, savolitinib, telisotuzumab vedotin, telisotuzumab adizutecan, and amivantamab. Additionally, emerging technologies such as circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) analyses have been investigated for their potential to improve MET alterations detection. This review also highlights studies that demonstrate the potential of MET ctDNA and CTC analyses to predict treatment responses and identify resistance mechanisms in MET-targeted therapies.

This therapeutic agent addresses a critical unmet need within a molecularly defined NSCLC subpopulation, marking a substantial advancement in c-Met-targeted oncology. The regulatory authorization and clinical use of telisotuzumab vedotin may significantly advance precision medicine for NSCLC, though an ongoing phase III trial will further confirm its efficacy and safety and determine its eligibility for full regulatory approval in the future.