What specific efficacy and safety results are expected from the Phase 2 TRUST‑I and TRUST‑II trials for taletrectinib?
Answer
The press release you quoted does not contain the actual numerical results from the Phase 2 TRUST‑I and TRUST‑II studies of taletrectinib (IBTROZI™). It only announces that the companies will present new data from those trials at two upcoming scientific meetings (the IASLC 2025 World Conference on Lung Cancer in Barcelona and the ESMO 2025 Congress in Berlin).
Because the release does not disclose the trial outcomes, we can only outline what types of efficacy and safety information the companies are expected to share based on the design of the two studies and the typical data that are presented for a Phase 2 oncology trial in a ROS1‑positive non‑small‑cell lung‑cancer (NSCLC) population.
Below is a comprehensive, evidence‑based summary of the key efficacy and safety endpoints that are usually reported for TRUST‑I and TRUST‑II, and which the audience will likely expect to see when the data are finally presented.
| Category | Specific results that are typically reported (and therefore likely to be presented) |
|---|---|
| Efficacy | |
| • Overall Response Rate (ORR) – proportion of patients achieving a confirmed partial response (PR) or complete response (CR) per RECIST 1.1 criteria. • For a ROS1‑positive NSCLC cohort, a Phase 2 ORR in the 30 %–60 % range would be considered clinically meaningful and is the metric most often highlighted in early‑phase data. |
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| • Disease Control Rate (DCR) – proportion of patients with PR, CR, or stable disease (SD) lasting ≥ 6 weeks. • A DCR of ≥ 70 % would signal that taletrectinib is able to halt tumor progression in the majority of treated patients. |
|
| • Duration of Response (DoR) – median time that responders (those with PR/CR) maintain their response. • In prior ROS1‑targeted agents, median DoR has been ≈ 8–12 months; a comparable or longer DoR would reinforce durability of benefit. |
|
| • Progression‑Free Survival (PFS) – median time from first dose to disease progression or death. • A median PFS of ≈ 6–9 months in a ROS1‑positive NSCLC population would be a benchmark to compare against existing TKIs (e.g., crizotinib, entrectinib). |
|
| • Overall Survival (OS) – median overall survival, though OS data are often immature at the time of a Phase 2 presentation. • Any trend toward > 12 months would be encouraging. |
|
| • Time to Response – how quickly responses are observed after treatment initiation (often reported as median time to first response). | |
| • Subgroup Analyses – efficacy in patients with brain metastases, prior TKI exposure, or different ROS1 fusion partners. | |
| Safety | |
| • Adverse‑Event (AE) Profile – incidence of treatment‑emergent AEs (any grade) and grade ≥ 3 AEs. • For a selective ROS1/TRK inhibitor, the most common ≥ Grade 3 AEs historically include elevated liver enzymes, fatigue, and gastrointestinal toxicities; the company will likely present the frequency of each. |
|
| • Serious Adverse Events (SAEs) – number and type of events leading to hospitalization, life‑ threatening situations, or death. | |
| • Treatment‑Discontinuation Rate – proportion of patients who stop taletrectinib permanently because of AEs. • A low discontinuation rate (< 10 %) would underscore a manageable safety profile. |
|
| • Dose‑Modification Frequency – percentage of patients requiring dose reductions or interruptions due to toxicity. | |
| • Laboratory Abnormalities – rates of clinically relevant lab changes (e.g., ALT/AST elevations, neutropenia, hyperglycemia). | |
| • Cardiovascular and Neurologic Safety – incidence of QTc prolongation, arrhythmias, or neurologic AEs (e.g., dizziness, neuropathy) that are sometimes observed with multi‑kinase inhibitors. | |
| • Safety in Special Populations – data on patients with pre‑existing hepatic or renal impairment, or those receiving concomitant CNS‑active therapies. | |
| Comparative Context | |
| • Benchmark vs. Existing ROS1 TKIs – the company will likely position the ORR, DCR, PFS, and safety data relative to crizotinib, entrectinib, or lorlatinib, highlighting any improvements in efficacy or reductions in off‑target toxicities. | |
| • Potential Biomarker Insights – any correlation between specific ROS1 fusion partners (e.g., CD74‑ROS1, EZR‑ROS1) and response magnitude or safety signals. | |
| Regulatory Implications | |
| • Data Package for Future Registrations – the Phase 2 results are expected to form the core of a registration‑enabling dataset for potential FDA/EMA submissions, especially if the efficacy signals are robust and the safety profile is favorable. |
Bottom‑Line Take‑Away
- The press release does not yet provide the actual numbers; it only signals that the TRUST‑I (likely the first ROS1‑positive NSCLC cohort) and TRUST‑II (perhaps a confirmatory or expanded cohort) Phase 2 studies will be discussed at the WCLC and ESMO meetings.
- Stakeholders can anticipate that the presentation will focus on the key efficacy metrics listed above—ORR, DCR, DoR, PFS, and early OS—along with a detailed safety overview (overall AE rates, grade ≥ 3 AEs, SAEs, discontinuations, and dose modifications).
- The data will be contextualized against existing ROS1‑targeted therapies to illustrate whether taletrectinib offers a higher response rate, longer disease control, or a more tolerable safety profile.
When the full abstract or slide deck from the conference becomes publicly available (e.g., via the conference website, a press release, or a peer‑reviewed publication), those specific percentages, median durations, and safety frequencies can be extracted and reported. Until then, the above outline captures the type of efficacy and safety results that are expected to be disclosed for the Phase 2 TRUST‑I and TRUST‑II trials of taletrectinib.