Phase 3 Randomized Double‑Blind Study of Adjuvant Taletrectinib Versus Placebo in Completely Resected Stage IB‑IIIA ROS1‑Fusion Positive Non‑Small Cell Lung Cancer

The primary objective is to evaluate the efficacy of taletrectinib versus placebo by measuring disease-free survival in patients with completely resected ROS1‑fusion positive non‑small cell lung cancer, irrespective of receipt of postoperative adjuvant chemotherapy. Secondary objectives include:

• Further comparative assessment of efficacy between taletrectinib and placebo.
• Characterization of the pharmacokinetic profile of taletrectinib.
• Evaluation of safety and tolerability of taletrectinib relative to placebo.

The trial enrolled 135 participants diagnosed with non‑small cell lung cancer harboring ROS1 rearrangements. Eligible individuals were adults (≥18 years) of any gender who had undergone curative resection of stage IB, II, or IIIA disease and demonstrated an Eastern Cooperative Oncology Group performance status of 0 or 1. All participants had documented ROS1 fusion by a validated assay performed in a CLIA‑certified laboratory, and adequate tumor tissue was available for central confirmation. Enrollment required complete postoperative recovery, with surgery performed between 4 and 30 weeks prior to randomization depending on receipt of adjuvant chemotherapy, and any chemotherapy‑related toxicities resolved to ≤Grade 1. The study population included both male and female patients and encompassed individuals considered vulnerable, provided they met the specified clinical and pathological criteria.

The study is a multicenter, Phase 3, randomized, double‑blind, placebo‑controlled trial evaluating oral taletrectinib 400 mg capsules versus matching placebo as adjuvant therapy in patients with ROS1‑fusion positive non‑small cell lung cancer who have undergone complete tumor resection (stage IB‑IIIA). Eligible participants are randomized in a 1:1 ratio after a screening visit confirming histology, ROS1 status, surgical margins, performance status, and recovery from surgery or prior adjuvant chemotherapy. The trial schedule includes a baseline/randomization visit, regular follow‑up visits for safety monitoring, disease‑free survival assessment, laboratory tests, ECGs, and pharmacokinetic sampling, and concludes with an end‑of‑study visit performed at disease recurrence, withdrawal, or after the planned observation period, which may extend up to five years. Recruitment began in July 2026 and the overall study is projected to close in August 2033, resulting in a participant involvement period of up to five years of follow‑up. Early termination of individual participation may occur if a participant experiences disease recurrence, withdraws consent, or is discontinued for safety or protocol‑compliance reasons.

The investigational product is Taletrectinib, supplied as oral capsules containing 400 mg of the active substance. Each dose consists of a single 400 mg capsule administered by the oral route in accordance with the study dosing schedule.

The comparator is a matching placebo capsule, formulated to be indistinguishable from the active capsules and containing no active pharmaceutical ingredient.

Both study medications are taken orally as directed by the protocol, and dosing compliance is monitored through patient diaries and capsule count at each study visit. Administration timing and any dose modifications are recorded in the case report form to ensure adherence to the prescribed regimen.

Efficacy will be evaluated primarily by disease‑free survival as determined by investigator assessment, defined as the time from randomization to documented tumor recurrence or death from any cause. Secondary efficacy parameters include DFS rates assessed at 2, 3, 4, and 5 years, overall survival, DFS evaluated by blinded independent central review (BICR), OS rates at the same annual timepoints, and central nervous system (CNS) DFS assessed by both investigator assessment and BICR. Plasma concentrations of taletrectinib will be measured to support pharmacokinetic‑efficacy correlations, and safety outcomes such as adverse events will be graded according to CTCAE v5.0.

Investigator assessments of DFS and CNS DFS will be performed at scheduled study visits, with annual evaluations at years 2 through 5 for rate calculations. BICR will independently review imaging data using a predefined, blinded protocol to corroborate investigator findings. Plasma samples for drug concentration analysis will be collected at designated timepoints according to the pharmacokinetic sampling schedule and analyzed with a validated assay. All efficacy data will be analyzed descriptively and with time‑to‑event statistical methods appropriate for survival endpoints.