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.
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.
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.
Parallel
Taletrectinib
DrugApproximately 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.
Crizotinib
DrugApproximately 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.
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
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.
ORR
Proportion of subjects with the best overall confirmed response of complete response (CR) or partial response (PR) according to RECIST v1.1 criteria.
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.
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
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