The purpose of this phase 3 multicenter double-blind randomized study is to assess the use of taletrectinib in the early-stage non-small cell lung cancer (NSCLC). The study compares taletrectinib (study drug) versus placebo (sugar pill) in patients with ROS1-fusion positive stage IB, II, IIIA NSCLC. The study will evaluate if taletrectinib is better than placebo at preventing the participant's disease from coming back after the participant's lung tumor was removed.

Inclusion Criteria:

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

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

3. 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.

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 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:

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

   1. 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.

   2. 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.

   3. 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.

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

   5. 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.

2. Any investigational therapy for any condition other than NSCLC within 6 months of Randomization.

3. Co-mutations of epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) fusion.

4. 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.

5. Have clinically significant cardiovascular disease within 3 months prior to Randomization.

6. Have a known history of uncontrolled hypertension.

7. 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).

8. 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.

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

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