Phase 3 Study of Taletrectinib vs Placebo as an Adjuvant Therapy in ROS1 Positive NSCLC (TRUST-IV)

Inclusion criteria

• Histologically confirmed stage IB, II, or IIIA NSCLC (AJCC 9th edition) based on pathological staging.
• Documented ROS1 rearrangement in primary tumor by a validated local assay performed in CLIA-certified or locally equivalent diagnostic laboratories.
• Adequate tissue is available for prospective central laboratory confirmatory testing. Confirmation of central test positivity is required prior to Randomization.

Note: In the event that the local testing assay is the same as the central testing assay, and the local test was conducted in a CLIA-certified laboratory or local equivalent, prospective central confirmation is not needed, but tumor tissue must still be provided for other biomarker studies.

• Age ≥18 years (or ≥20 years as required by local regulations).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Received definitive locoregional curative surgery for stage IB, II, or IIIA NSCLC. All surgical margins of resection must be negative for tumor.
• Complete recovery from surgery (including complete wound healing) that was performed ≥4 weeks but no more than 16 weeks before Randomization if no adjuvant chemotherapy was given. Surgery must have occurred ≥4 weeks but no more than 30 weeks prior to Randomization if adjuvant chemotherapy was given. For participants who received post-resection adjuvant chemotherapy, the final dose of chemotherapy must also have occurred at least 7 days before Randomization. All chemotherapy related toxicities must have resolved to baseline or ≤Grade 1 (per CTCAE v5.0) prior to Randomization.

Exclusion criteria

• Has previously received 1 or more of the following cancer treatments:

• Postoperative or planned radiation therapy for the current lung cancer. Note: radiotherapy in the neoadjuvant setting is allowed and must be completed at least 4 weeks prior to Randomization.
• Any adjuvant anticancer therapy (including investigational therapy) for treatment of NSCLC other than standard postoperative platinum-based doublet chemotherapy. Participants should have received no more than 4 cycles of the platinum doublet regimen.

Notes: Adjuvant immune checkpoint inhibitor (ICI) treatment is allowed, but participants should have received no more than 4 cycles of the ICI, and at the time of Randomization, have at least 12 weeks of washout from the last dose of the ICI. Any prior immune-related toxicity, such as immune-related hepatitis, colitis, or pneumonitis, must be completely resolved prior to Randomization.

• Neoadjuvant chemotherapy with or without ICIs is allowed. Those treated with prior ICIs are eligible if ≥12 weeks have elapsed after completion of the ICI at the time of Randomization. Any prior immune-related toxicity (if an ICI was given), such as immune-related hepatitis, colitis, or pneumonitis, must be completely resolved prior to Randomization.
• Major surgery (including surgical resection of the primary tumor but excluding placement of vascular access port) within 4 weeks of Randomization.
• Segmentectomies or wedge resections, instead of complete resections, of the primary tumor. Note: These limited resections are allowed for patients with stage IB disease with T2aN0M0, with tumor size >3 to ≤4 cm, and without visceral pleura or central invasion.
• Any investigational therapy for any condition other than NSCLC within 6 months of Randomization.
• Co-mutations of epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) fusion.
• History of other malignancies except adequately treated non-melanoma skin cancer, curatively treated in situ cancer, or other tumors curatively treated with no evidence of disease for >3 years after the end of treatment and which, in the opinion of the treating physician, do not have a substantial risk of recurrence of the prior malignancy.
• Have clinically significant cardiovascular disease within 3 months prior to Randomization.
• Have a known history of uncontrolled hypertension.
• Experiencing ongoing cardiac dysrhythmias of ≥Grade 2 (CTCAE v5.0), uncontrolled atrial fibrillation of any CTCAE grade, a QT interval corrected by Fridericia's formula (QTcF) of >470 milliseconds, symptomatic bradycardia <45 bpm; undergoing treatment with medication(s) known to be associated with the development of Torsades de Pointes (TdP).
• Have active and clinically significant bacterial, fungal, or viral infection, including hepatitis B virus (HBV), hepatitis C virus (HCV); or known human immunodeficiency virus (HIV)- or acquired immunodeficiency syndrome-related illness.
• Currently have or have a history of interstitial lung disease (ILD), drug-related pneumonitis, or radiation pneumonitis that required steroid treatment.
• Use of food or drugs that are known as strong cytochrome P450 (CYP)3A inducers or inhibitors within 14 days prior to Randomization.