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JYP0322 Versus Platinum Based Doublet Chemotherapy in ROS1 Positive Patients Previously Treated With ROS1-TKIs.

Not Applicable
Not yet recruiting
Conditions
Non Small Cell Lung Cancer
Interventions
Drug: JYP0322 tablets
Drug: Cross-over to JYP0322
Registration Number
NCT07154368
Lead Sponsor
Guangzhou JOYO Pharma Co., Ltd
Brief Summary

The primary purpose of the study was to compare progression-free survival of JYP0322 vs. platinum-based doublet chemotherapy in patients previously treated with ROS1-TKIs. Patients in the chemotherapy arm are given the option to switch to JYP0322 after BICR confirmed progressive disease (PD), while also have the choice to pursue with other drugs after discussing with their physicians.

Detailed Description

This is a phase III, open label, randomized study assessing JYP0322 (150 mg, orally, tid) versus platinum-based doublet chemotherapy in subjects with confirmed diagnosis of ROS1 fusion positive NSCLC, who have progressed following prior therapy with one or two approved ROS1 Tyrosine Kinase Inhibitor (ROS1-TKI) agents and whose tumors harbors a ROS1 fusion positive. Subjects must agree to provide a biopsy for central confirmation of ROS1 fusion status. A total of 207 patients will be randomly assigned in a 2:1 ratio to receive oral JYP0322 (at a dose of 150mg tid) or intravenous pemetrexed (500 mg per square meter of body-surface area) plus carboplatin (target area under the curve 5 \[AUC5\]) every 3 weeks for up to six cycles. Patients without disease progression after four cycles of platinu

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
207
Inclusion Criteria
  • Key Inclusion Criteria

    • Subjects with histologically or cytologically documented NSCLC.
    • Locally advanced or metastatic ROS1 fusion positive NSCLC.
    • Prior one or two ROS1-TKI(s) Treatment.
    • World Health Organization (WHO) performance status 0-1.
    • Life expectancy of at least 3 months.
    • At least one measurable lesion according to RECISIT 1.1.
Exclusion Criteria
  • Key Exclusion Criteria:

    • Current participation in another therapeutic clinical trial.
    • Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact on drug absorption.
    • A history of severe allergies, or a history of severe allergy, hypersensitivity or other hypersensitivity to any active or inactive ingredient of the study drug.
    • All acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 Grade more than 1.
    • Any investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment.
    • Known active infe

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
JYP0322 tabletsJYP0322 tablets-
Pemetrexed DisodiumPemetrexed injection-
Pemetrexed DisodiumCross-over to JYP0322-
Primary Outcome Measures
NameTimeMethod
Progression Free Survival (PFS) by BICR AssessmentUP to 3 years

Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Progressive Disease (PD): \>= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of \>=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. PFS is the time from date of randomization until the date of PD (by BICR assessment) or death (due to any cause) regardless of whether the patient withdrew from randomized therapy. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST 1.1 assessment.

Secondary Outcome Measures
NameTimeMethod
Progression Free Survival (PFS) by investigators AssessmentUP to 3 years

Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by MRI or CT: Progressive Disease (PD): \>= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of \>=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. PFS is the time from date of randomization until the date of PD (by investigators assessment) or death (due to any cause) regardless of whether the patient withdrew from randomized therapy. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST 1.1 assessment

Overall Survival (OS)UP to 5 years

OS is defined as the time from date of randomization until the date of death (due to any cause) regardless of whether the patient withdrew from randomized therapy. Patients who had not died would be censored at the last known alive date.

Objective Response Rate (ORR) by Investigator and BICR assessmentRECIST tumor assessments every 6 weeks from randomization up to 3 years.

Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): \>= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. ORR is the percentage of patients with at least 1 visit response of CR or PR prior to progression or any further therapy.

Duration of Response (DOR) by Investigator and BICR assessmentRECIST tumor assessments every 6 weeks from randomization up to 3 years.

Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): \>= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. DOR is the time from the date of first documented response until the date of documented progression or death in the absence of disease progression for patients who had conformed CR or PR.

Disease Control Rate (DCR) by Investigator and BICR assessmentRECIST tumor assessments every 6 weeks from randomization up to 3 years.

Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): \>= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions; Stable disease (SD): Neither sufficient shrinkage to qualify as a response nor sufficient growth to qualify as progression; Progressive Disease (PD): \>= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of \>=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. DCR is the percentage of patients with best response of CR, PR or SD at \>=6 weeks, prior to any progressive disease (PD).

Time to Response (TTR) by Investigator and BICR assessmentRECIST tumor assessments every 6 weeks from randomization up to 3 years.

Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): \>= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions; Stable disease (SD): Neither sufficient shrinkage to qualify as a response nor sufficient growth to qualify as progression; TTR is defined as time from the date of randomization to the first documented response for patients who had confirmed CR or PR at least once.

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