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

NCT07154706 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: AB-106-G319
• Study Type: interventional
• Target: 180
• Locations: 3 countries
• Sites: 29

Brief Summary

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.

Conditions

Non-small Cell Lung Cancer (NSCLC)

Keywords

NSCLC; Adjuvant; ROS1; Stage IB; Stage II; Stage IIIA; Resection

Outcome Measures

Primary Outcomes (1)

• Primary Outcome Measure: To compare the efficacy of taletrectinib with that of placebo, as measured by disease-free survival (DFS) by investigator assessment.

  Measure Description: Defined as the time from the date of randomization until the date of disease recurrence or death (by any cause in the absence of recurrence) by investigator's assessment.

  Time Frame: Up to approximately 5 years after the first patient is randomized (maximum follow-up of 70 months).

Secondary Outcomes (7)

• Secondary Outcome Measure: DFS rates by investigator assessment at 2, 3, 4, and 5 years.

  Time Frame: Up to approximately 5 years after the first patient is randomized (maximum follow-up of 70 months). DFS rate 2 years (%), 3 years (%), 4 years (%), and 5 years (%) are presented.

• Secondary Outcome Measure: Overall Survival (OS).

  Time Frame: Up to approximately 7 years after the first patient is randomized (maximum follow-up of 86 months).

• Secondary Outcome Measure: DFS by blinded independent central review (BICR).

  Time Frame: Up to approximately 5 years after the first patient is randomized (maximum follow-up of 70 months).

• Secondary Outcome Measure: OS rates at 2, 3, 4, and 5 years.

  Time Frame: Up to approximately 7 years after the first patient is randomized (maximum follow-up of 86 months). DFS rate 2 years (%), 3 years (%), 4 years (%), and 5 years (%) are presented.

• Secondary Outcome Measure: Central nervous system (CNS) DFS by Investigator assessment and by BICR.

  Time Frame: Up to approximately 5 years after the first patient is randomized (maximum follow-up of 70 months).

Study Arms (2)

Taletrectinib Active Arm

ACTIVE COMPARATOR

Active Arm

Drug: Taletrectinib

Placebo Arm

PLACEBO COMPARATOR

Placebo Arm

Drug: Placebo

Interventions

Taletrectinib DRUG

Intervention Label: Taletrectinib Intervention Name: Taletrectinib Dosage Formulation: Capsule Unit Dose Strength(s): 200 mg Dosage Level (s): 400 mg QD Route of Administration: Oral Use: Experimental IMP and NIMP/AxMP : IMP Former Name(s) or Alias(es): AB-106.

Also known as: AB-106

Taletrectinib Active Arm

Placebo DRUG

Intervention Label: Placebo Intervention Name: Placebo Type: Drug Dosage Formulation: Capsule Unit Dose Strength(s): 200 mg Dosage Level(s): 400 mg QD Route of Administration: Oral Use: Placebo Comparator IMP and NIMP/AxMP: IMP Former Name(s) or Alias(es): Placebo

Placebo Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nuvation Bio Inc.: lead

Study Sites (29)

UCLA

Los Angeles, California, 90404, United States

RECRUITING

UCI Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

RECRUITING

Georgetown University Medical Cener (GUMC)

Washington D.C., District of Columbia, 20007, United States

RECRUITING

Saint Alphonsus Health System

Boise, Idaho, 83706, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Sarah Cannon Research Institute (SCRI) - Texas Oncology-Central South

Austin, Texas, 78731, United States

RECRUITING

MD Anderson

Houston, Texas, 45559, United States

RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

Princess Margaret Cancer Centre-University Health Network

Toronto, Ontario, MG5 1Z5, Canada

RECRUITING

McGill University

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Peking University People's Hospital

Beijing, Beijing Municipality, 100044, China

RECRUITING

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510163, China

RECRUITING

Guangxi Medical University Cancer Hospital

Nanning, Guangxi, 530221, China

RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450003, China

RECRUITING

Tongji Hospital Tongji Medical College of HUST

Wuhan, Hubei, 430030, China

RECRUITING

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, 210000, China

RECRUITING

Nantong Tumor Hospital

Nantong, Jiangsu, 226300, China

RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

RECRUITING

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710061, China

RECRUITING

Cancer Hospital of Shandong First Medical University

Jinan, Shandong, 250117, China

RECRUITING

Linyi Cancer Hospital

Linyi, Shandong, 276034, China

RECRUITING

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200120, China

RECRUITING

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

RECRUITING

West China Hospital of Sichuan University

Chengdu, Sichuan, 610000, China

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

taletrectinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2025
• First Posted: September 4, 2025
• Study Start: August 21, 2025
• Primary Completion (Estimated): August 30, 2030
• Study Completion (Estimated): August 30, 2033
• Last Updated: April 14, 2026

Record last verified: 2026-04

Locations

CA (2); US (10); CN (17)