A Phase III Study Comparing Taletrectinib With Standard Therapy in ROS1 Positive Locally Advanced or Metastatic Non-small Cell Lung Cancer Patients
NCT Number: NCT06564324
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Non Small Cell Lung Cancer
Interventions: DRUG: Taletrectinib|DRUG: Crizotinib
Sponsor: AnHeart Therapeutics Inc.
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 138
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09
Completion Date: 2030-09

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.

Primary Outcome Measures: 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 Outcome Measures: PFS (Assessed by investigator), 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., About 69months|ORR, Proportion of subjects with the best overall confirmed response of complete response (CR) or partial response (PR) according to RECIST v1.1 criteria., About 69 months|DOR, 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., About 69 months|DCR, 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, About 69 months|TTR, Defined as the overall time from the time of tumor occurrence to the patient's death. Response assessments are per RECIST v1.1 criteria., About 69 months|OS, Defined as the time from the first dose to death due to any cause., About 69 months|IC-TTP, 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., About 69 months|IC-ORR, 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., About 69 months|IC-DOR, 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., About 69 months|IC-PFS, 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, About 69 months|IC-PR at 6, 12, 18, 24, and 36 months, Partial response at 6, 12, 18, 24, and 36 months on CNS metastatic subjects, Assessed by the BIRC, per RECIST v1.1 criteria., About 69 months|AE, Adverse event, including the events reported following physical examination, vital signs assessment, clinical laboratory assessment or electrocardiogram(ECG), About 69 months|Taletrectinib concentration in plasma, Defined as the relationship between taletrectinib concentration and time in the body, About 12 months, at the begining of cycle 1, cycle 2, cycle 7 and cycle 12（each cycle is 28 days）|patient-reported outcomes(PRO) assessed by EORTC QLQ-C30, 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., About 69 months|PRO assessed by EORTC QLQ-L13, 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., About 69 months|PRO assessed by EQ-5D-5L, 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., About 69 months