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

Inclusion Criteria:

1. Histologically confirmed stage IB, II, or IIIA NSCLC (AJCC 9th edition) based onpathological staging.

2. Documented ROS1 rearrangement in primary tumor by a validated local assay performedin CLIA-certified or locally equivalent diagnostic laboratories.

3. Adequate tissue is available for prospective central laboratory confirmatorytesting. 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 testingassay, and the local test was conducted in a CLIA-certified laboratory or localequivalent, prospective central confirmation is not needed, but tumor tissue muststill be provided for other biomarker studies.

4. Age ≥18 years (or ≥20 years as required by local regulations).

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

6. Received definitive locoregional curative surgery for stage IB, II, or IIIA NSCLC.All surgical margins of resection must be negative for tumor.

7. Complete recovery from surgery (including complete wound healing) that was performed ≥4 weeks but no more than 16 weeks before Randomization if no adjuvant chemotherapywas given. Surgery must have occurred ≥4 weeks but no more than 30 weeks prior toRandomization if adjuvant chemotherapy was given. For participants who receivedpost-resection adjuvant chemotherapy, the final dose of chemotherapy must also haveoccurred at least 7 days before Randomization. All chemotherapy related toxicitiesmust have resolved to baseline or ≤Grade 1 (per CTCAE v5.0) prior to Randomization.

Exclusion Criteria:

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

2. Postoperative or planned radiation therapy for the current lung cancer. Note:radiotherapy in the neoadjuvant setting is allowed and must be completed atleast 4 weeks prior to Randomization.

3. Any adjuvant anticancer therapy (including investigational therapy) fortreatment of NSCLC other than standard postoperative platinum-based doubletchemotherapy. Participants should have received no more than 4 cycles of theplatinum doublet regimen.Notes: Adjuvant immune checkpoint inhibitor (ICI) treatment is allowed, butparticipants should have received no more than 4 cycles of the ICI, and at thetime of Randomization, have at least 12 weeks of washout from the last dose ofthe ICI. Any prior immune-related toxicity, such as immune-related hepatitis,colitis, or pneumonitis, must be completely resolved prior to Randomization.

4. Neoadjuvant chemotherapy with or without ICIs is allowed. Those treated withprior ICIs are eligible if ≥12 weeks have elapsed after completion of the ICIat the time of Randomization. Any prior immune-related toxicity (if an ICI wasgiven), such as immune-related hepatitis, colitis, or pneumonitis, must becompletely resolved prior to Randomization.

5. Major surgery (including surgical resection of the primary tumor but excludingplacement of vascular access port) within 4 weeks of Randomization.

6. Segmentectomies or wedge resections, instead of complete resections, of theprimary tumor. Note: These limited resections are allowed for patients withstage IB disease with T2aN0M0, with tumor size >3 to ≤4 cm, and withoutvisceral pleura or central invasion.

7. Any investigational therapy for any condition other than NSCLC within 6 months ofRandomization.

8. Co-mutations of epidermal growth factor receptor (EGFR) or anaplastic lymphomakinase (ALK) fusion.

9. History of other malignancies except adequately treated non-melanoma skin cancer,curatively treated in situ cancer, or other tumors curatively treated with noevidence of disease for >3 years after the end of treatment and which, in theopinion of the treating physician, do not have a substantial risk of recurrence ofthe prior malignancy.

10. Have clinically significant cardiovascular disease within 3 months prior toRandomization.

11. Have a known history of uncontrolled hypertension.

12. Experiencing ongoing cardiac dysrhythmias of ≥Grade 2 (CTCAE v5.0), uncontrolledatrial fibrillation of any CTCAE grade, a QT interval corrected by Fridericia'sformula (QTcF) of >470 milliseconds, symptomatic bradycardia <45 bpm; undergoingtreatment with medication(s) known to be associated with the development of Torsadesde Pointes (TdP).

13. Have active and clinically significant bacterial, fungal, or viral infection,including hepatitis B virus (HBV), hepatitis C virus (HCV); or known humanimmunodeficiency virus (HIV)- or acquired immunodeficiency syndrome-related illness.

14. Currently have or have a history of interstitial lung disease (ILD), drug-relatedpneumonitis, or radiation pneumonitis that required steroid treatment.

15. Use of food or drugs that are known as strong cytochrome P450 (CYP)3A inducers orinhibitors within 14 days prior to Randomization.