A Phase III Study Comparing Taletrectinib With Standard Therapy in ROS1 Positive Locally Advanced or Metastatic Non-small Cell Lung Cancer Patients

NCT ID: NCT06564324

Last Updated: 2025-11-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

138 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-27

Study Completion Date

2030-09-30

Brief Summary

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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

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Conditions

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Non Small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Taletrectinib

69 ROS1-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer patients will be enrolled in Arm A and treated with talerectinib

Group Type EXPERIMENTAL

Taletrectinib

Intervention Type DRUG

Approximately 138 ROS-1TKI- 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 treated until they experience progressive disease (PD) assessed by the blinded Independent Review Committee (BIRC), intolerable toxicity, or another discontinuation criterion is met.

Crizotinib

69 ROS1-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer patients will be enrolled in Arm B and treated with Crizotinib

Group Type ACTIVE_COMPARATOR

Crizotinib

Intervention Type DRUG

Approximately 138 ROS-1TKI- 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 treated until they experience progressive disease (PD) assessed by the blinded Independent Review Committee (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.

Interventions

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Taletrectinib

Approximately 138 ROS-1TKI- 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 treated until they experience progressive disease (PD) assessed by the blinded Independent Review Committee (BIRC), intolerable toxicity, or another discontinuation criterion is met.

Intervention Type DRUG

Crizotinib

Approximately 138 ROS-1TKI- 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 treated until they experience progressive disease (PD) assessed by the blinded Independent Review Committee (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.

Intervention Type DRUG

Eligibility Criteria

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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 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.
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 (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.
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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AnHeart Therapeutics Inc.

INDUSTRY

Sponsor Role collaborator

Nuvation Bio Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Caicun Zhou

Role: PRINCIPAL_INVESTIGATOR

Shanghai East Hospital

Locations

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The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, China

Site Status NOT_YET_RECRUITING

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Site Status RECRUITING

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Site Status NOT_YET_RECRUITING

Chongqing University Cancer Hospital

Chongqing, Chongqing Municipality, China

Site Status NOT_YET_RECRUITING

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, China

Site Status RECRUITING

The First Affiliated Hospital of Guangdong Pharmaceutical University

Guangzhou, Guangdong, China

Site Status NOT_YET_RECRUITING

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Site Status NOT_YET_RECRUITING

Guangxi Medical University Cancer Hospital

Nanning, Guangxi, China

Site Status RECRUITING

The Fourth Hospital of Hebei Medical University

Shijiazhuang, Hebei, China

Site Status NOT_YET_RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, China

Site Status NOT_YET_RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Site Status RECRUITING

Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, China

Site Status RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, China

Site Status RECRUITING

Jiangsu Province Hospital

Nanjing, Jiangsu, China

Site Status NOT_YET_RECRUITING

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Site Status RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Site Status NOT_YET_RECRUITING

The First Hospital of China Medical University

Shenyang, Liaoning, China

Site Status RECRUITING

Linyi Cancer Hospital

Linyi, Shandong, China

Site Status NOT_YET_RECRUITING

Cancer Hospital of Shandong First Medical University

Jinan, Shangdong, China

Site Status RECRUITING

Shanghai East Hospital

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, China

Site Status NOT_YET_RECRUITING

Shanxi Cancer Hospital

Taiyuan, Shanxi, China

Site Status NOT_YET_RECRUITING

The First Affiliated Hospital of Xi'an Jiaotong University

Xi’an, Shanxi, China

Site Status RECRUITING

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Site Status NOT_YET_RECRUITING

Tianjin Cancer Hospital

Tianjin, Tianjin Municipality, China

Site Status NOT_YET_RECRUITING

Yunnan Cancer Hospital

Kunming, Yunnan, China

Site Status NOT_YET_RECRUITING

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status NOT_YET_RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Site Status NOT_YET_RECRUITING

Countries

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China

Central Contacts

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Ying Zhao

Role: CONTACT

+86 13466689296

Facility Contacts

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Yiruo Zhang

Role: primary

Jun Zhao, MD

Role: primary

Jianchun Duan

Role: primary

Huiwen Ma

Role: primary

Jingxun Wu, MD

Role: primary

Xicheng Wang

Role: primary

Chengzhi Zhou

Role: primary

Qitao Yu, MD

Role: primary

Yun Zhao, MD

Role: backup

Cuimin Ding

Role: primary

Qiming Wang

Role: primary

Huijie Fan, MD

Role: primary

Qian Chu, MD

Role: primary

Yongchang Zhang, MD

Role: primary

Renhua Guo

Role: primary

Chuanyong Mu

Role: primary

Jianjun Tang

Role: primary

Bo Jin, MD

Role: primary

Jianhua Shi

Role: primary

Linlin Wang, MD

Role: primary

Caicun Zhou, MD

Role: primary

Shengxiang Ren, MD

Role: primary

Yuanlin Song

Role: primary

Wei Guo

Role: primary

Yu Yao, MD

Role: primary

Feng Luo

Role: primary

Peng Chen

Role: primary

Gaofeng Li

Role: primary

Yong Fang

Role: primary

Yun Fan

Role: primary

Other Identifiers

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AB-106-G318

Identifier Type: -

Identifier Source: org_study_id

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