A Multi-centered, Randomized, Open-label Phase III Study to Evaluate the Efficacy and Safety of TGRX-326 Comparing With Crizotinib in Patients of Advanced ALK-positive or Metastatic Non-Small Cell Lung Cancer
Overview
- Phase
- Phase 3
- Intervention
- TGRX-326
- Conditions
- Non Small Cell Lung Cancer
- Sponsor
- Shenzhen TargetRx, Inc.
- Enrollment
- 321
- Locations
- 1
- Primary Endpoint
- Progression Free Survival (PFS) by independent review committee (IRC)
- Status
- Active, not recruiting
- Last Updated
- 11 months ago
Overview
Brief Summary
This is a multi-center, randomized, open-label, Phase III clinical trial which compares the safety and efficacy of TGRX-326 with crizotinib in patients with ALK-positive advanced or metastatic NSCLC
Detailed Description
This Phase III study aims to evaluate the safety profile and efficacy profile in patients with ALK-positive advanced or metastatic NSCLC and to compare the efficacy and safety of TGRX-326 with that of crizotinib. The primary purpose of this study is to evaluate and compare the efficacy profile of TGRX-326 with crizotinib, with progression-free survival (PFS) as evaluated by independent review committee (IRC) as end point. Secondary objectives include comparing efficacy profile of other endpoints and safety profiles of the investigational drug with crizotinib. Exploratory objective includes the evaluation of population pharmacokinetic (PK) profile of TGRX-326 and efficacy of TGRX-326 in ALK-positive advanced NSCLC patients determined as progressive disease after crizotinib treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willing to follow the treatment protocol and visit schedule, and participate in the study with the ICF signed;
- •≥ 18 years of age on the day of ICF signing, regardless of gender.
- •Diagnosed as incurable stage IIIB - IV ALK-positive NSCLC;
- •Providing prior ALK positive test results at screening;
- •Naïve to ALK-inhibitor; patients could be intolerant or have progressive disease from previous first-line chemotherapy;
- •Patients could have metastases to central nervous system at screening if the condition is asymptomatic, stable or completely recovered;
- •At least one measurable lesion;
- •An ECOG PS score within 0-2;
- •Adequate bone marrow, liver, kidney, coagulation and pancreatic functions;
- •Expected survival ≥ 3 months;
Exclusion Criteria
- •Known hypersensitivity to any of the active ingredients or excipients of TGRX-326 or crizotinib pills; or a history of severe allergic reactions;
- •Having another type of cancer except for lung cancer;
- •Radiotherapy within 14 days prior to the first dose;
- •Received other systemic anti-tumor treatment within 4 weeks prior to the first dose, or is within 5 half-lives of the said treatment; received traditional Chinese medicine indicated for anti-tumor purposes within 14 days prior to the first dose;
- •Major surgery within 4 weeks prior to the first dose;
- •Spinal cord compression caused by tumor, unless the subject achieves significant pain control and full recovery of neurological function within 4 weeks prior to the first dose.
- •Abnormal gastrointestinal function that affect absorption within the past 6 months;
- •History of active pneumonia or clinically significant interstitial pneumonia, or radiation or drug-induced lung disorder with treatment needs;
- •Cardiac insufficiency;
- •Abnormal and clinically significant QTc on ECG or need of concomitant use of any drug known to prolong QT interval and cause torsades de pointes;
Arms & Interventions
TGRX-326
Subjects to be treated with the investigational drug TGRX-326 at 60 mg once day in 28-day cycles.
Intervention: TGRX-326
Crizotinib
Subjects to be treated with the active control drug crizotinib at 250 mg twice day in 28-day cycles.
Intervention: Crizotinib
Outcomes
Primary Outcomes
Progression Free Survival (PFS) by independent review committee (IRC)
Time Frame: Every 8 weeks between Cycle 1 and Cycle 17, and every 12 weeks from Cycle 17 and onwards (every cycle is 28 days); an average of 1.5 years
PFS defined by the time from randomization to progressive disease or death of any cause; PFS as evaluated by independent review committee (IRC).
Secondary Outcomes
- Progression Free Survival (PFS) by investigator(Every 8 weeks between Cycle 1 and Cycle 17, and every 12 weeks from Cycle 17 and onwards (every cycle is 28 days); an average of 1.5 years)
- Time to Response (TTR)(Every 8 weeks between Cycle 1 and Cycle 17, and every 12 weeks from Cycle 17 and onwards (every cycle is 28 days); an average of 1.5 years)
- Intracranial Disease Control Rate (IC-DCR)(Every 8 weeks between Cycle 1 and Cycle 17, and every 12 weeks from Cycle 17 and onwards (every cycle is 28 days); an average of 1.5 years)
- Intracranial Duration of Response (IC-DOR)(Every 8 weeks between Cycle 1 and Cycle 17, and every 12 weeks from Cycle 17 and onwards (every cycle is 28 days); an average of 1.5 years)
- Overall Survival (OS)(Every 8 weeks between Cycle 1 and Cycle 17, and every 12 weeks from Cycle 17 and onwards (every cycle is 28 days); an average of 1.5 years)
- Disease Control Rate (DCR)(Every 8 weeks between Cycle 1 and Cycle 17, and every 12 weeks from Cycle 17 and onwards (every cycle is 28 days); an average of 1.5 years)
- Adverse Events (AEs)(At Screening; Day 1 of every Cycle (each cycle is 28 days) until end of study)
- Serious Adverse Events (SAEs)(At Screening; Day 1 of every Cycle (each cycle is 28 days) until end of study)
- One-year Progression Free Survival (PFS)(Every 8 weeks between Cycle 1 and Cycle 17, and every 12 weeks from Cycle 17 and onwards (every cycle is 28 days); an average of 1.5 years)
- Duration of Response (DOR)(Every 8 weeks between Cycle 1 and Cycle 17, and every 12 weeks from Cycle 17 and onwards (every cycle is 28 days); an average of 1.5 years)
- Intracranial Progression Free Survival (IC-PFS)(Every 8 weeks between Cycle 1 and Cycle 17, and every 12 weeks from Cycle 17 and onwards (every cycle is 28 days); an average of 1.5 years)
- Objective Response Rate (ORR)(Every 8 weeks between Cycle 1 and Cycle 17, and every 12 weeks from Cycle 17 and onwards (every cycle is 28 days); an average of 1.5 years)
- Intracranial Objective Response Rate (IC-ORR)(Every 8 weeks between Cycle 1 and Cycle 17, and every 12 weeks from Cycle 17 and onwards (every cycle is 28 days); an average of 1.5 years)
- Intracranial Time to Response (IC-TTR)(Every 8 weeks between Cycle 1 and Cycle 17, and every 12 weeks from Cycle 17 and onwards (every cycle is 28 days); an average of 1.5 years)