AbbVie is gearing up to seek accelerated approval for telisotuzumab vedotin (Teliso-V) following positive results from the pivotal phase 2 LUMINOSITY trial. The antibody-drug conjugate (ADC) targets c-Met and is being developed as a treatment for patients with relapsed or refractory non-squamous, non-small cell lung cancer (NSCLC) whose tumors overexpress c-Met. The FDA has granted breakthrough therapy designation to Teliso-V, acknowledging its potential to significantly improve outcomes in this patient population.
LUMINOSITY Trial Results
The LUMINOSITY trial, involving 233 patients, evaluated Teliso-V as a second- or third-line treatment after prior therapies, including chemotherapy and immunotherapy. The study revealed a 35% overall response rate (ORR) in patients with high c-Met expression and 23% in those with intermediate levels. These results are supported by a median duration of response of 9 months and 7.2 months, and a median overall survival of 14.6 months and 14.2 months, respectively.
Clinical Significance of c-Met Targeting
c-Met overexpression is observed in approximately 25% of advanced EGFR wild-type NSCLC patients and is associated with poor prognosis. The c-Met protein is implicated in both driving cancer progression and enabling resistance to common NSCLC therapies, such as EGFR inhibitors. Teliso-V's mechanism of action offers a potential solution to overcome this resistance.
Ongoing and Future Studies
AbbVie has initiated the phase 3 TeliMET-NSCLC-01 trial, which will compare Teliso-V monotherapy to docetaxel chemotherapy in c-Met-positive, non-squamous NSCLC patients, both with and without other gene mutations, including EGFR and ALK. Furthermore, Teliso-V is being investigated in combination with AstraZeneca’s EGFR inhibitor Tagrisso (osimertinib), Roche’s EGFR inhibitor Tarceva (nilotinib), or Bristol Myers Squibb’s PD-1 inhibitor Opdivo (nivolumab) in the phase 1 M14-237 study across various c-Met-expressing solid tumors.
Competitive Landscape
While several c-Met-targeting drugs, such as Novartis’ Tabrecta (capmatinib), Merck KGaA’s Tepmetko (tepotinib), and Hutchmed’s Orpathys (savolitinib), have gained approval, these therapies target specific c-Met mutations (Metex14) present in only 3% to 4% of NSCLC patients. Teliso-V, on the other hand, targets c-Met protein overexpression, which is more prevalent, offering a broader therapeutic application.
