Emrelis (telisotuzumab vedotin-tllv)

Encouragingly, several MET TKIs such as capmatinib, tepotinib, and savolitinib have been approved for the treatment of MET exon 14 skipping mutations. On 14 May 2025, the U.S. Food and Drug Administration granted accelerated approval to telisotuzumab vedotin-tllv for adult patients with locally advanced or metastatic non-squamous NSCLC whose tumors exhibit high c-Met protein overexpression and who have already received prior systemic therapy. In this review, we summarize the structure and physiological role of the MET receptor, the molecular mechanisms underlying aberrant MET activation, its contribution to acquired resistance against targeted therapies, and emerging strategies for effectively targeting MET alterations in NSCLC.

The success of inhibitors like sotorasib and adagrasib has expanded options for targeting once 'undruggable' oncogenic drivers such as KRAS...ADCs such as EMRELIS™, Datroway, and ELAHERE™ offer precise targeting along with potent cytotoxic agents...Cancer vaccine research is progressing with licensed immunoprophylactic drugs, and AI tools like AlphaFold are speeding up drug discovery by enhancing structural biology predictions. This review covers recent cancer therapeutics advancements, including targeted inhibitors, immunotherapies, resistance strategies, epigenetic interventions, combination therapies, vaccines, and AI applications.

P2, N=60, Not yet recruiting, Jonsson Comprehensive Cancer Center

In phase Ib studies, TV-t combined with osimertinib achieved a 50% ORR and 7.4-month PFS, while TV-t with nivolumab, the median PFS was 7.2 months, but ORR was low (7.4%). TV-t demonstrated promising efficacy and tolerability in patients, highlighting its clinical potential. However, further studies are needed to confirm its survival advantage, the durability of response, and safety profile, and to establish its long-term value and support its integration into routine clinical practice.

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