AbbVie Seeks Accelerated FDA Approval for Telisotuzumab Vedotin in c-Met Overexpressing NSCLC
核心洞察
AbbVie (搜索) has submitted a Biologics License Application (BLA) to the FDA for telisotuzumab vedotin to treat NSCLC with c-Met protein (搜索) overexpression.
The BLA is supported by Phase 2 LUMINOSITY trial data, which showed promising overall response rates in c-Met high and intermediate patients.
Telisotuzumab vedotin, an antibody-drug conjugate, targets c-Met-overexpressing tumors and could be a first-in-class therapy if approved.
AbbVie (搜索) has announced the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for accelerated approval of telisotuzumab vedotin (Teliso-V) for adult patients with previously treated, locally advanced or metastatic epidermal growth factor receptor (EGFR (搜索)) wild type, nonsquamous non-small cell lung cancer (搜索) (NSCLC) with c-Met protein (搜索) overexpression.
This submission marks a significant step toward providing a potential new treatment option for a subset of NSCLC patients with limited alternatives. Approximately 85% of lung cancers are classified as NSCLC, remaining the leading cause of cancer-related deaths worldwide.
The c-Met protein (搜索), a receptor tyrosine kinase, is overexpressed in roughly 25% of advanced EGFR (搜索) wild type, nonsquamous NSCLC cases and is linked to a poorer prognosis. Telisotuzumab vedotin (Teliso-V) is being developed for this patient population, which currently has very limited treatment options.
Clinical Efficacy
The BLA is supported by data from the Phase 2 LUMINOSITY trial (Study M14-239), an ongoing study evaluating the safety and efficacy of telisotuzumab vedotin in c-Met overexpressing NSCLC populations. The LUMINOSITY trial is designed to identify NSCLC populations that overexpress c-Met best suited for Teliso-V monotherapy in the second-line or third-line setting, and then to expand the groups to further evaluate efficacy in the selected populations. The trial's endpoints include overall response rate (ORR), duration of response (DoR), disease control rate (DCR) and progression-free survival (PFS) per independent central review (ICR) as well as overall survival (OS).
Data from the LUMINOSITY study presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting showed promising results:
- In patients with high c-Met expression (n = 78), the objective response rate (ORR) was 34.6% (95% CI, 24.2%-46.2%).
- In patients with intermediate c-Met expression (n = 83), the ORR was 22.9% (95% CI, 14.1%-33.4%).
- In the overall c-Met overexpression group (n = 161), the ORR was 28.6% (95% CI, 21.7%-36.2%).
Additionally, the median duration of response (DOR) was 9.0 months (95% CI, 4.2-13.0), 7.2 months (95% CI, 5.3-11.5), and 8.3 months (95% CI, 5.6-11.3) in the high, intermediate, and overall c-Met overexpression groups, respectively. Responses lasting six months or longer were observed in 63.0%, 47.4%, and 56.5% of patients in each group.
The median progression-free survival (PFS) was 5.5 months (95% CI, 4.1-8.3) in the c-Met high group, 6.0 months (95% CI, 4.5-8.1) in the c-Met intermediate group, and 5.7 months (95% CI, 4.6-6.9) in the total c-Met overexpression group. The median overall survival (OS) was 14.6 months (95% CI, 9.2-25.6), 14.2 months (95% CI, 9.6-16.6), and 14.5 months (95% CI, 9.9-16.6) in each respective cohort.
Safety Profile
Any-grade treatment-related adverse effects (TRAEs) occurred in 81.4% of patients, with 27.9% experiencing grade 3 or higher TRAEs. Common any-grade TRAEs included peripheral sensory neuropathy (30.2%), peripheral edema (16.3%), fatigue (14.0%), and diminished appetite (11.6%). No new safety signals were identified.
Mechanism of Action
Telisotuzumab vedotin is an investigational, first-in-class, c-Met protein (搜索)-directed antibody-drug conjugate (ADC) designed to target c-Met overexpressing tumors. It utilizes a microtubule polymerization inhibitor, monomethyl auristatin E (MMAE), as its payload.
Ongoing and Future Studies
Telisotuzumab vedotin is also being evaluated as a monotherapy in the randomized Phase 3 confirmatory global study TeliMET NSCLC-01 (NCT04928846) in patients with previously treated c-Met overexpressing NSCLC. Enrollment in this study is ongoing across global clinical trial sites.
Management Commentary
"Patients with non-small cell lung cancer (搜索) have unmet medical needs and oncologists are looking for new treatment options for these patients who unfortunately have a poor prognosis," said Roopal Thakkar, M.D., executive vice president, research and development, chief scientific officer, AbbVie (搜索). "We are hopeful that Teliso-V will be a differentiated treatment for certain patients as we look to elevate the standards of care in oncology."
Regulatory Status
In December 2021, telisotuzumab vedotin was granted Breakthrough Therapy Designation by the FDA.