A Phase III Study Comparing Taletrectinib With Standard Therapy in ROS1 Positive Locally Advanced or Metastatic Non-small Cell Lung Cancer Patients
- Conditions
- Non Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT06564324
- Lead Sponsor
- Nuvation Bio Inc.
- Brief Summary
This is a Phase 3, randomized, open-label, comparative, multicenter, international study for NSCLC patients whose tumor tissue exhibits ROS1 fusion positivity (i.e., ROS1+) and who have not previously received an ROS1-targeted TKI (i.e., ROS1-TKI-naïve).
Approximately 138 ROS-1 TKI- naïve ROS1+NSCLC patients will be randomized in a 1:1 ration to one of 2 study arms:
* Arm A: Taletrectinib monotherapy at 600 mg once daily (QD), continuously;
* Arm B: Crizotinib monotherapy at 250 mg twice daily (BID), continuously. Each cycle duration will be 28 days.
Participants will be stratified by the presence of intracranial metastases at baseline (Yes versus No) and prior chemotherapy use for locally advanced or metastatic disease (Yes versus No). For the purposes of stratification, prior chemotherapy is defined as completion of ≥1 cycle of chemotherapy in the locally advanced or metastatic setting. Participants will be treated until they experience progressive disease (PD) assessed by the BIRC, intolerable toxicity, or another discontinuation criterion is met. Crossover from control group (crizotinib) to taletrectinib is also permitted, at the Investigator's discretion with the Sponsor's approval, for qualifying participants who have experienced objective progression confirmed by the BIRC.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 138
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Histologically or cytologically confirmed diagnosis of locally advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC.
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Have documentation of ROS1 rearrangement by a positive result
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Have at least 1 measurable (i.e., target) lesion by Investigator assessment per RECIST v1.1.
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Prior brain or leptomeningeal 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.
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Age ≥18 years (or ≥20 years as required by local regulations).
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Eastern Cooperative Oncology Group (ECOG) performance status zero (0) to 1.
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Minimum life expectancy of 3 months or more.
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Adequate organ function meeting the following criteria:
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): ≤3.0 × upper limit of normal (ULN) (or ≤5.0 × ULN, for participants with concurrent liver metastases).
- Serum total bilirubin: ≤1.5 × ULN (≤3.0 × ULN for participants with Gilbert syndrome).
- Absolute neutrophil count: ≥1500/μL.
- Platelet count: ≥75,000/μL.
- Hemoglobin: ≥9.0 g/dL.
- 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).
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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.
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The participant is willing and capable of giving written informed consent.
- Previously received an investigational antineoplastic agent for NSCLC.
- Previously received any prior TKI, including ROS1-targeted TKIs.
- Received immune checkpoint inhibitors for locally advanced or metastatic disease.
- Previously received more than 1 regimen of systemic anticancer therapy for locally advanced or metastatic disease.
- Had major surgery within 28 days prior to randomization. Minor surgical procedures, such as catheter placement or minimally invasive biopsy, are allowed.
- Have symptomatic CNS metastases (parenchymal or leptomeningeal) 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.
- Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Participants with leptomeningeal disease and without cord compression are allowed.
- 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).
- 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.
- 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.
- Have a known history of uncontrolled hypertension. Participants with hypertension should be under treatment on study entry to control blood pressure.
- 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 .
- 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
- Currently have or have a history of interstitial lung disease (ILD), drug-related pneumonitis, or radiation pneumonitis that required steroid treatment.
- Be pregnant or breastfeeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Taletrectinib Taletrectinib 69 ROS1-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer patients will be enrolled in Arm A and treated with talerectinib Crizotinib Crizotinib 69 ROS1-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer patients will be enrolled in Arm B and treated with Crizotinib
- Primary Outcome Measures
Name Time Method PFS (Assessed by BIRC) About 49 months Progression-Free-Survival, The time between the beginning of treatment and the occurrence of disease progression or death. Assessed by the blinded Independent Review Committee (BIRC), per RECIST v1.1
- Secondary Outcome Measures
Name Time Method IC-PFS About 69 months Defined as the time between the beginning of treatment and the occurrence of disease progression or death on CNS metastatic subjects, Assessed by the BIRC, per RECIST v1.1 criteria
PFS (Assessed by investigator) About 69months Progression-Free-Survival is defined as the time between the beginning of treatment and the occurrence of disease progression or death. Assessed by the investigator, per RECIST v1.1 criteria.
ORR About 69 months Proportion of subjects with the best overall confirmed response of complete response (CR) or partial response (PR) according to RECIST v1.1 criteria.
DOR About 69 months Defined as the time from the first date of objective response (CR or PR) to the first documented date of disease progression. Response assessments are per RECIST v1.1 criteria.
DCR About 69 months Defined as the proportion of subjects with a best overall response of CR, PR or stable disease per RECIST v1.1 criteria) as assessed by the investigator
OS About 69 months Defined as the time from the first dose to death due to any cause.
TTR About 69 months Defined as the overall time from the time of tumor occurrence to the patient's death. Response assessments are per RECIST v1.1 criteria.
IC-TTP About 69 months Defined as the overall time from the time of tumor occurrence with CNS(central nervous system) metastases to the patient's death, Assessed by the BIRC, per RECIST v1.1 criteria.
IC-ORR About 69 months Proportion of CNS metastatic subjects with the best overall confirmed response of complete response (CR) or partial response (PR), Assessed by the BIRC, per RECIST v1.1 criteria.
IC-DOR About 69 months Defined as the time from the first date of objective response (CR or PR) to the first documented date of disease progression on CNS metastatic subjects. Assessed by the BIRC, per RECIST v1.1 criteria.
IC-PR at 6, 12, 18, 24, and 36 months About 69 months Partial response at 6, 12, 18, 24, and 36 months on CNS metastatic subjects, Assessed by the BIRC, per RECIST v1.1 criteria.
AE About 69 months Adverse event, including the events reported following physical examination, vital signs assessment, clinical laboratory assessment or electrocardiogram(ECG)
Taletrectinib concentration in plasma About 12 months, at the begining of cycle 1, cycle 2, cycle 7 and cycle 12（each cycle is 28 days） Defined as the relationship between taletrectinib concentration and time in the body
PRO assessed by EQ-5D-5L About 69 months Patient-reported outcomes of health-related quality of life, assessed by EQ-5D-5L, the scale measures range in score from 0 to 100, a high score for the health status represents a high quality of life.
patient-reported outcomes(PRO) assessed by EORTC QLQ-C30 About 69 months Patient-reported outcomes of health-related quality of life, assessed by EORTC QLQ-C30, the single-item measures range in score from 0 to 4 or 7, a high score for a symptom scale represents a high level of symptomatology / problems.
PRO assessed by EORTC QLQ-L13 About 69 months Patient-reported outcomes of health-related quality of life, assessed by EORTC QLQ-LC13, the single-item measures range in score from 0 to 4, a high score for a symptom scale represents a high level of symptomatology / problems.
Trial Locations
- Locations (11)
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
The First Affiliated Hospital of Xiamen University
🇨🇳Xiamen, Fujian, China
Guangxi Medical University Cancer Hospital
🇨🇳Nanning, Guangxi, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
The First Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Cancer Hospital of Shandong First Medical University
🇨🇳Jinan, Shangdong, China
Shanghai East Hospital
🇨🇳Shanghai, Shanghai, China
Shanghai Pulmonary Hospital
🇨🇳Shanghai, Shanghai, China
The First Affiliated Hospital of Xi'an Jiaotong University
🇨🇳Xi'an, Shanxi, China