Phase II study of telisotuzumab vedotin in patients with c–MET+ NSCLC who have previously received not more than 2 lines prior systemic therapy (Abstract # 9016)
Telisotuzumab vedotin is an anti-c-MET antibody-drug conjugate (ADC) composed of the monoclonal antibody that is linked to monomethyl auriastatin E (MMAE). In the Phase I Study (MN14-237), Teliso-V is being administered with osimertinib to patients with NSCLC with c-MET overexpression that has been previously treated. Recently the drug has received Breakthrough Therapy Designation (BTD) as monotherapy by the FDA for its use in patients with advanced or metastatic EGFR-wt non-squamous NSCLC whose cancer has advanced or progressed after being treated with platinum-based therapy.
Results from Phase I/Ib in patients receiving Teliso-V and osimertinib in patients having EGFR L858R, ex 19 deletions, and c-MET overexpression. The combination of Teliso-V and osimertinib showed an ORR of 58%. The ORR of Teliso-V as per its dosing was 3 (43%) out of 7 patients receiving Teliso-V 1.6 mg/kg and 8 (67%) out of 12 patients receiving 1.9 mg/kg Teliso-V dosage.
AbbVie presented an interim analysis from the Phase II LUMINOSITY trial, which included 136 patients, out of which 122 were evaluable for the primary endpoint. The primary endpoint was the objective response rate (ORR) per independent central review. According to the Bayesian model, the probability of at least 70% of true ORR is >25% to advance stage 2. Treatment-emergent adverse events (TEAEs) of any grade were observed in 131 (96%) of patients, and Grade 3+ adverse events were observed in 65 (48% of patients).
KOL insights
“Patients with NSCLC have a high unmet need, and telisotuzumab vedotin has the potential to provide them with an additional treatment option to manage their disease.”–Expert Opinion.
Conclusion
Antibody-drug conjugates (ADCs) are a class of anti-cancer therapy that can transport cytotoxic drugs directly to tumor cells, thus affecting the strengths of both cytotoxic chemotherapy and targeted therapy. ADCs are rapidly establishing their place and have already shown promising preliminary data in lung cancer. There are currently various ADCs in clinical trials targeting HER2, HER3, TROP2, CEACAM5, and MET in NSCLC.
C-mesenchymal-epithelial transition factor (c-MET) is an oncogene tyrosine kinase receptor. c-MET can regulate a variety of cellular functions and dysregulation of, which can induce proliferation, survival, invasion, and metastatic of tumor cells. c-MET alterations in NSCLC include point mutations, amplification, fusion, and protein overexpression, which are associated with poor prognosis. Previous preclinical and clinical studies suggested that MET activation is both a primary oncogenic driver mutation and a secondary driver of acquired resistance to targeted therapy in other genomic subpopulations. Therefore, agents targeting c-MET are a promising treatment strategy for NSCLC. Currently, no targeted drug has been approved explicitly targeting c-MET overexpressing NSCLC. So getting a BTD can prove crucial in the approval of first and foremost therapy in this patients segment, giving this molecule a first-mover advantage in the market.
Companies- Janssen, Cullinan Oncology, Immutep, Bristol Myers Squibb, Merck Sharp & Dohme, Surface Oncology, AbbVie, Daiichi Sankyo, Chugai Pharmaceutical, Regeneron, Sanofi, and others
