Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The pivotal trial LUMINOSITY reported an overall response rate (ORR) of 35% and a median duration of response (DOR) of 7.2 months for telisotuzumab vedotin in a single-arm study. However, there is no head-to-head comparator data available, and the evidence lacks the robustness typically expected from Phase III trials, which limits the ability to claim superiority over existing treatments.
Cost effectiveness
No cost-utility analyses, incremental costs, or ICERs for telisotuzumab vedotin were identified in the retrieved sources. The absence of economic evaluations prevents any assessment of cost-effectiveness, which is critical for HTA decisions.
Quality of life
There is a complete absence of HRQoL data in the retrieved sources, including no validated instruments or longitudinal outcomes reported. This lack of information indicates a significant gap in understanding the treatment’s impact on patients’ quality of life.
Supporting Domains
Safety and Adverse Effects
The safety profile reported in the LUMINOSITY trial indicates that common adverse reactions include peripheral neuropathy (51%) and pneumonia (13%), with serious adverse reactions occurring in 35% of patients. While there are notable adverse effects, the overall safety profile is acceptable, with manageable risks.
Comparator Selection
The confirmatory Phase III trial is designed to compare telisotuzumab vedotin against docetaxel, which is relevant as a standard of care. However, the pivotal trial lacks head-to-head data, which raises concerns about the robustness of the comparator selection.
Patient Population and Subgroups
The pivotal trial population is primarily composed of EGFR wild-type patients with high c-Met overexpression, but there are significant limitations in demographic representation, particularly for Black and Hispanic populations. This limits the generalizability of the findings.
Care Pathway Integration
The treatment can be integrated into existing pathways with some adjustments, such as the requirement for specific diagnostic testing for c-Met overexpression. The administration route is manageable, requiring IV administration every two weeks.
Resource Use and Cost Implications
While the treatment may have manageable budget impacts, the lack of economic data raises concerns about the overall resource burden. The absence of cost-utility analyses makes it difficult to assess the broader implications on healthcare resources.
Evidence Quality and Robustness
The evidence is primarily based on a single-arm trial with no comparative data available. While the trial design is acceptable, the lack of robust Phase III data and ongoing confirmatory trials introduces uncertainty regarding the overall evidence quality.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties regarding the treatment’s long-term effectiveness and safety, particularly due to the absence of comparative data and economic evaluations. The demographic limitations in the trial population also raise concerns about equity and access.
