Comparing Taletrectinib with Standard Therapy for ROS1 Positive Lung Cancer

A Phase 3 Multicenter Open-label Study of Taletrectinib Versus a Standard of Care ROS1-Tyrosine Kinase Inhibitor (Crizotinib) in TKI-Naïve Patients With ROS1-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer (TRUST-III)

This study is testing if a new drug called Taletrectinib works better than the standard treatment Crizotinib for people with ROS1 positive lung cancer who haven't had treatment before.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 194 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Nuvation Bio Inc. (Industry-sponsored)
• Drugs / interventions: radiation, Taletrectinib, Crizotinib, chemotherapy
• Locations: 29 sites (Hefei, Anhui and 28 other locations)
• Trial ID: NCT06564324 on ClinicalTrials.gov

What this trial studies

This Phase 3, randomized, open-label study evaluates the efficacy of Taletrectinib compared to Crizotinib in patients with ROS1 positive, locally advanced or metastatic non-small cell lung cancer (NSCLC) who have not previously received ROS1-targeted therapy. Approximately 138 participants will be randomly assigned to receive either Taletrectinib or Crizotinib, with treatment continuing until disease progression is observed. The study will also stratify participants based on the presence of intracranial metastases and prior chemotherapy use.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 or older with confirmed ROS1 positive locally advanced or metastatic NSCLC who have not received prior ROS1-targeted therapy.

Not a fit: Patients with symptomatic CNS metastases requiring increasing doses of corticosteroids or anticonvulsants may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective treatment option for patients with ROS1 positive NSCLC.

How similar studies have performed: Other studies have shown promising results with ROS1-targeted therapies, indicating potential success for this approach.

Eligibility criteria

Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of locally advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC.
2. Have documentation of ROS1 rearrangement by a positive result
3. Have at least 1 measurable (i.e., target) lesion by Investigator assessment per RECIST v1.1.
4. Prior brain metastases allowed if asymptomatic and diagnosed incidentally at study baseline. If participants have neurological symptoms or signs due to CNS metastasis, participants need to complete local therapy (surgery and/or radiation) at least 7 days before enrollment and be clinically stable without requiring for an increasing dose of corticosteroids or use of anticonvulsants to control symptoms.
5. Age ≥18 years (or ≥20 years as required by local regulations).
6. Eastern Cooperative Oncology Group (ECOG) performance status zero (0) to 1.
7. Minimum life expectancy of 3 months or more.
8. Adequate organ function meeting the following criteria:

   1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): ≤3.0 × upper limit of normal (ULN) (or ≤5.0 × ULN, for participants with concurrent liver metastases).
   2. Serum total bilirubin: ≤1.5 × ULN (≤3.0 × ULN for participants with Gilbert syndrome).
   3. Absolute neutrophil count: ≥1500/μL.
   4. Platelet count: ≥75,000/μL.
   5. Hemoglobin: ≥9.0 g/dL.
   6. Estimated creatinine clearance (CLcr) ≥45 mL/min as calculated using the method standard for the institution (e.g., Cockcroft-Gault Equation, i.e., CCr={((140-age)×weight)/(72×SCr)}×0.85 (if female) (Cockcroft and Gault 1976).
9. All toxicities from prior anticancer therapy have resolved to ≤ Grade 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0), or have resolved to previous baseline, at the time of randomization.
10. The participant is willing and capable of giving written informed consent.

Exclusion Criteria:

1. Previously received an investigational antineoplastic agent for NSCLC.
2. Previously received any prior TKI, including ROS1-targeted TKIs.
3. Received immune checkpoint inhibitors for locally advanced or metastatic disease.
4. Previously received more than 1 regimen of systemic anticancer therapy for locally advanced or metastatic disease.
5. Had major surgery within 28 days prior to randomization. Minor surgical procedures, such as catheter placement or minimally invasive biopsy, are allowed.
6. Have symptomatic CNS metastases at Screening or asymptomatic disease requiring an increasing dose of corticosteroids to control symptoms within 7 days prior to randomization. Participants with no prior history of signs or symptoms of CNS metastases but who receive prophylactic steroids or anticonvulsants are allowed.
7. Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Participants with leptomeningeal disease and without cord compression are allowed.
8. Uncontrolled pleural, abdominal, or pericardial effusion within 28 days prior to randomization, which is associated with malignant effusion requiring recurrent drainage procedures (once monthly or more frequently).
9. Have been diagnosed with another primary malignancy other than NSCLC except for adequately treated nonmelanoma skin cancer or cervical cancer in situ; definitively treated nonmetastatic prostate cancer; or participants with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
10. Have clinically significant cardiovascular diseases within 6 months prior to randomization: myocardial infarction, severe/unstable angina, coronary/peripheral endovascular treatment, heart failure, cerebrovascular disorder including transient ischemic attack, pulmonary embolism, deep venous thrombosis and or other clinically significant thrombosis.
11. Have a known history of uncontrolled hypertension. Participants with hypertension should be under treatment on study entry to control blood pressure.
12. Have ongoing cardiac dysrhythmias of ≥CTCAE Grade 2, uncontrolled atrial fibrillation of any grade, or QT interval corrected for heart rate by Fredericia's formula (QTcF) \>470 milliseconds (female) or \>450 milliseconds (male), or symptomatic bradycardia \<45 bpm within 6 months before enrollment; participants treated with medications known to be associated with the development of TdP .
13. Have active and clinically significant bacterial, fungal, or viral infection including but not limited to hepatitis B virus (HBV), hepatitis C virus (HCV), known HIV or AIDS-related illness
14. Currently have or have a history of interstitial lung disease (ILD), drug-related pneumonitis, or radiation pneumonitis that required steroid treatment.
15. Be pregnant or breastfeeding

Where this trial is running

Hefei, Anhui and 28 other locations

• The First Affiliated Hospital of Anhui Medical University — Hefei, Anhui, China (Recruiting)
• Beijing Cancer Hospital — Beijing, Beijing Municipality, China (Recruiting)
• Cancer Hospital Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China (Not_yet_recruiting)
• Chongqing University Cancer Hospital — Chongqing, Chongqing Municipality, China (Recruiting)
• The First Affiliated Hospital of Xiamen University — Xiamen, Fujian, China (Recruiting)
• The First Affiliated Hospital of Guangdong Pharmaceutical University — Guangzhou, Guangdong, China (Recruiting)
• The First Affiliated Hospital of Guangzhou Medical University — Guangzhou, Guangdong, China (Recruiting)
• Guangxi Medical University Cancer Hospital — Nanning, Guangxi, China (Recruiting)
• The Fourth Hospital of Hebei Medical University — Shijiazhuang, Hebei, China (Recruiting)
• Henan Cancer Hospital — Zhengzhou, Henan, China (Not_yet_recruiting)
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (Recruiting)
• Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)
• Hunan Cancer Hospital — Changsha, Hunan, China (Recruiting)
• Jiangsu Province Hospital — Nanjing, Jiangsu, China (Recruiting)
• The First Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (Recruiting)
• The First Affiliated Hospital of Nanchang University — Nanchang, Jiangxi, China (Recruiting)
• The First Hospital of China Medical University — Shenyang, Liaoning, China (Recruiting)
• Linyi Cancer Hospital — Linyi, Shandong, China (Recruiting)
• Cancer Hospital of Shandong First Medical University — Jinan, Shangdong, China (Recruiting)
• Shanghai East Hospital — Shanghai, Shanghai Municipality, China (Recruiting)
• Shanghai Pulmonary Hospital — Shanghai, Shanghai Municipality, China (Recruiting)
• Zhongshan Hospital, Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)
• Shanxi Cancer Hospital — Taiyuan, Shanxi, China (Recruiting)
• The First Affiliated Hospital of Xi'an Jiaotong University — Xi’an, Shanxi, China (Recruiting)
• West China Hospital of Sichuan University — Chengdu, Sichuan, China (Recruiting)
• Tianjin Cancer Hospital — Tianjin, Tianjin Municipality, China (Recruiting)
• Yunnan Cancer Hospital — Kunming, Yunnan, China (Not_yet_recruiting)
• Sir Run Run Shaw Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Recruiting)
• Zhejiang Cancer Hospital — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Caicun Zhou — Shanghai East Hospital
• Study coordinator: Ying Zhao

Conditions Non Small Cell Lung Cancer