With more than 500,000 cases in the 7MM, lung cancer is one of the leading causes of death worldwide. This condition is often diagnosed when the patient reaches the advanced, inoperable, or metastatic stage, adversely affecting their quality of life. With so many biomarker-driven therapies in the approved line and the emerging pipeline, telisotuzumab adizutecan, a c-MET-targeting ADC delivering adizutecan (a stable linker to minimize toxicity), AbbVie's Proprietary Topoisomerase 1 (TOP1) inhibitor. 

In a Phase I study (NCT05029882), Temab-A demonstrated manageable safety and promising efficacy in patients with advanced NSCLC who had progressed on standard therapies. Tumor reduction was observed in all 38 patients with post-baseline data, irrespective of EGFR alterations (e.g., L858R, exon 19 deletions) or TKI resistance mutations such as T790M and C797S, and across varying levels of c-Met expression. Among 41 evaluable patients, the confirmed ORR was 63%, with a clinical benefit rate (CBR12) of 83%, a median Duration of Response of 13 months, and a median PFS of 9 months. At the data cutoff February 11, 2025, 24% of patients remained on treatment, underscoring the potential of Temab-A as a durable and effective treatment option in this resistant and high-unmet-need population.

KOL insights

Antibody-drug conjugates like telisotuzumab adizutecan are designed to deliver cytotoxic agents directly to cancer cells while sparing healthy tissue. AbbVie’s data comes at a time when the market for targeted therapies in NSCLC continues to expand, with researchers and pharmaceutical companies seeking innovative solutions for unmet medical needs.” – Expert Opinion

Conclusion

NSCLC is increasingly becoming a biomarker-driven market. EGFR is one of the profitable biomarker segments, with many blockbuster therapies. The approach to direct EGFR mutation while being its inhibitor has become conventional. Temab-A brings the idea of being a c-MET inhibitor and targeting EGFR-mutated NSCLC. The two main approved c-MET inhibitors are TABRECTA (capmatinib) and TEPMETKO (tepotinib), which are highly specific for targeting MET exon 14 skipping mutations. These mutations are relatively common in NSCLC, and c-MET inhibitors have shown good efficacy in clinical trials, especially in the first-line treatment setting. The use of c-MET inhibitors in combination with EGFR-Tyrosine Kinase Inhibitors (TKIs) is being investigated. This approach is particularly relevant for patients with EGFR-mutated NSCLC who have developed resistance to EGFR-TKIs, and who also have MET alterations. Some studies have shown promising results with combining c-MET inhibitors with EGFR-TKIs, suggesting that this approach may be a viable option for treating EGFR-mutated NSCLC with resistance to EGFR-TKIs and MET alterations.