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

NCT06564324 | Recruiting Phase 3 DMC

• 1 other identifier: AB-106-G318
• Study Type: interventional
• Target: 194
• Locations: 1 country
• Sites: 29

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 194 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);
• Arm B: Crizotinib monotherapy at 250 mg twice daily (BID). 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.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• PFS (Assessed by BIRC)

  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

  About 49 months

Secondary Outcomes (16)

• PFS (Assessed by investigator)

  About 69months

• ORR

  About 69 months

• DOR

  About 69 months

• DCR

  About 69 months

• TTR

  About 69 months

Study Arms (2)

Taletrectinib

EXPERIMENTAL

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

Drug: Taletrectinib

Crizotinib

ACTIVE COMPARATOR

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

Drug: Crizotinib

Interventions

Taletrectinib DRUG

Approximately 194 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); Arm B: Crizotinib monotherapy at 250 mg twice daily (BID). 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.

Taletrectinib

Crizotinib DRUG

Approximately 194 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); Arm B: Crizotinib monotherapy at 250 mg twice daily (BID). 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.

Crizotinib

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed diagnosis of locally advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC.
• Have documentation of ROS1 rearrangement by a positive result
• Have at least 1 measurable (i.e., target) lesion by Investigator assessment per RECIST v1.1.
• 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.
• Age ≥18 years (or ≥20 years as required by local regulations).
• Eastern Cooperative Oncology Group (ECOG) performance status zero (0) to 1.
• Minimum life expectancy of 3 months or more.
• 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).
• 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.

You may not qualify if:

• 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 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

Sponsors & Collaborators

• Nuvation Bio Inc.: lead

Study Sites (29)

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

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

taletrectinib; Crizotinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines

Study Officials

• Caicun Zhou

  Shanghai East Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ying Zhao

CONTACT

+86 13466689296; Ying.Zhao@nuvationbio.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2024
• First Posted: August 21, 2024
• Study Start: November 27, 2024
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): September 1, 2030
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

CN (29)