A Phase 3 Multicenter Double-blind Randomized Study of Taletrectinib Versus Placebo in Patients With ROS1-Fusion Positive Stage IB-IIIA Non-Small Cell Lung Cancer Who Have Undergone Complete Tumor Resection

Plain English Summary

Phase 3 Study of Taletrectinib vs Placebo as an Adjuvant Therapy in ROS1 Positive NSCLC (TRUST-IV) is a Phase 3 clinical trial sponsored by Nuvation Bio Inc. studying Non-small Cell Lung Cancer (NSCLC). This study tests if taletrectinib, an anti-cancer drug, is better than a placebo (sugar pill) at preventing ROS1-positive non-small cell lung cancer from returning after surgery. It is for patients with early-stage (IB-IIIA) non-small cell lung cancer that has a specific genetic marker called ROS1 rearrangement, and who have had their tumor surgically removed. Participants will receive either taletrectinib or a placebo, and will be closely monitored. The study is double-blind, meaning neither patients nor doctors will know who is receiving the active drug. Alternative treatments might include standard chemotherapy after surgery, or observation. The best option depends on individual circumstances and should be discussed with a doctor. The trial aims to enroll 180 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are 18 or older (or 20 in some regions), have early-stage NSCLC with a ROS1 rearrangement, and have had surgery to remove the tumor with clear margins. You cannot join if you have had certain prior cancer treatments like radiation therapy for this lung cancer, or specific types of immunotherapy or chemotherapy, or if you have other significant health conditions like uncontrolled high blood pressure or heart problems. Your cancer must be staged as IB, II, or IIIA, and you must have a good general health status (ECOG 0 or 1) to participate. This trial is studying Non-small Cell Lung Cancer (NSCLC), so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary goal is to see if taletrectinib helps keep the cancer away for longer after surgery compared to a placebo, measured by how long patients remain disease-free. The specific primary outcome measures are: Primary Outcome Measure: To compare the efficacy of taletrectinib with that of placebo, as measured by disease-free survival (DFS) by investigator assessment. (Time Frame: Up to approximately 5 years after the first patient is randomized (maximum follow-up of 70 months).). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a critical need for effective adjuvant therapies to prevent the recurrence of ROS1-positive non-small cell lung cancer after surgery, a group that currently has limited options. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Non-small Cell Lung Cancer (NSCLC), where improved treatment options are needed.

Investor Insight

This Phase 3 trial for taletrectinib, a targeted therapy for a specific lung cancer mutation, signals strong investor confidence in its potential to fill a significant unmet need in the adjuvant setti Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of taletrectinib versus other post-surgery treatment options. Understand that you will be randomly assigned to receive either the study drug or a placebo, and that participation involves regular clinic visits, tests, and monitoring for side effects. Be prepared for potential side effects and discuss any new or worsening symptoms with your healthcare team promptly. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: TRIPLE
• Enrollment: 180 participants

Interventions

• DRUG: Taletrectinib — 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.
• DRUG: Placebo — 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

Primary Outcomes

• Primary Outcome Measure: To compare the efficacy of taletrectinib with that of placebo, as measured by disease-free survival (DFS) by investigator assessment. (Time Frame: Up to approximately 5 years after the first patient is randomized (maximum follow-up of 70 months).)

Secondary Outcomes

• 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).)

Full Eligibility Criteria

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.

Trial Locations

• UCLA, Los Angeles, California, United States
• UCI Chao Family Comprehensive Cancer Center, Orange, California, United States
• Georgetown University Medical Cener (GUMC), Washington D.C., District of Columbia, United States
• Saint Alphonsus Health System, Boise, Idaho, United States
• Dana Farber Cancer Institute, Boston, Massachusetts, United States
• Mayo Clinic, Rochester, Minnesota, United States
• Memorial Sloan Kettering Cancer Center, New York, New York, United States
• Sarah Cannon Research Institute (SCRI) - Texas Oncology-Central South, Austin, Texas, United States
• MD Anderson, Houston, Texas, United States
• Virginia Cancer Specialists, Fairfax, Virginia, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Non-small Cell Lung Cancer (NSCLC)
• ROS1-fusion Positive Lung Cancer
• Adjuvant Therapy
• Targeted Cancer Therapy
• Oncology
• Lung Cancer Surgery
• Cancer Recurrence
• Molecularly Defined Cancers
• Genomic Medicine
• Precision Medicine

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