This study is a multi-center, open-label, dose-finding phase Ib clinical study with extension phase, which is aimed at evaluating the efficacy and safety of GB226 combined with fruquintinib in treatment of relapsed or metastatic NSCLC patients with EGFR-sensitive mutations who have failed to respond to EGFR-TKI treatment,evaluating the pharmacokinetic characteristics of GB226 and fruquintinib, and the immunogenicity of GB226, and preliminarily evaluating the antitumor activity of GB226 and fruquintinib.
Name: GB226
Description: GB226 210mg，q2w，ivgtt.Type: DrugGB226+Fruquintinib
Name: Fruquintinib
Description: Fruquintinib 3mg or 4mg or 5mg, qd.po. 3 weeks-on,1 week-offType: DrugGB226+Fruquintinib
Description: Assessment of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v4.03
Measure: Incidence of Adverse Event Time: all adverse events will be recorded from the time the consent form is signed through 90 days following cessation of treatment.Description: Assessment of serious adverse events (SAEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v4.03
Measure: Incidence of Serious Adverse Event Time: all adverse events will be recorded from the time the consent form is signed through 90 days following cessation of treatment.Description: Incidence of Dose Limited Toxicity
Measure: Dose Limited Toxicity Time: Day 1 to Day 28 after first doseDescription: Defined as the highest dose tested in which only 0 or 1 out of 6 evaluable patients experience a dose limiting toxicity, as graded by the National Cancer Institute (NCI) Common terminology Criteria for Adverse Events (CTCAE) version 4.03
Measure: Maximum Tolerated Dose Time: Day 1 to Day 28 after first doseDescription: Objective response rate in accordance with RECIST 1.1. ORR will be calculated as the percent of patients in each of the expansion cohorts whose best confirmed response is complete response (CR) or partial response (PR).
Measure: ORR Time: up to 52 weeksDescription: Progression-free survival. From start of treatment to time of progression or death, whichever occurs first
Measure: PFS Time: up to 52 weeksDescription: Duration of Response. Date of CR or PR to Date of Objective Disease Progression or Death from Any Cause.
Measure: DOR Time: up to 52 weeksDescription: Disease control rate.DCR will be the proportion of patients in each of the expansion cohorts whose best confirmed response is CR, PR, or stable disease (SD).
Measure: DCR Time: up to 52 weeksDescription: Overall Survival. From start of treatment to time of death.
Measure: OS Time: up to 52 weeksDescription: incidence of anti-GB226 antibody(ADA)
Measure: ADA Time: up to 52 weeksDescription: Pharmacokinetics of GB226 and Fruquinitinib by assessment of Cmax
Measure: Cmax Time: up to 16 weeksDescription: Pharmacokinetics of GB226 and Fruquinitinib by assessment of AUC
Measure: AUC Time: up to 16 weeksSingle Group Assignment
There are 4 SNPs
Inclusion Criteria: 1. Aged 18-75 years, male or female; 2. Understanding the procedures and contents of the study, and voluntarily signing the written informed consent form; 3. Histologically or cytology confirmed relapsed or metastatic NSCLC; 4. EGFR gene sensitive mutation is confirmed positive, any of following is met: exon 19 deletion (19DEL), exon 21 point mutation (L858R / L861Q), 18 exon point mutation (G719X), 20 exon point mutation (S768I). --- L858R ---
Inclusion Criteria: 1. Aged 18-75 years, male or female; 2. Understanding the procedures and contents of the study, and voluntarily signing the written informed consent form; 3. Histologically or cytology confirmed relapsed or metastatic NSCLC; 4. EGFR gene sensitive mutation is confirmed positive, any of following is met: exon 19 deletion (19DEL), exon 21 point mutation (L858R / L861Q), 18 exon point mutation (G719X), 20 exon point mutation (S768I). --- L858R --- --- L861Q ---
Inclusion Criteria: 1. Aged 18-75 years, male or female; 2. Understanding the procedures and contents of the study, and voluntarily signing the written informed consent form; 3. Histologically or cytology confirmed relapsed or metastatic NSCLC; 4. EGFR gene sensitive mutation is confirmed positive, any of following is met: exon 19 deletion (19DEL), exon 21 point mutation (L858R / L861Q), 18 exon point mutation (G719X), 20 exon point mutation (S768I). --- L858R --- --- L861Q --- --- S768I ---
No T790M mutation after failure of EGFR-TKI treatment; 2. T790M mutation after EGFR-TKI treatment failure, and failed to respond to third-generation EGFR-TKI treatment; primary T790M mutation, progressed after third-generation EGFR-TKI treatment or no other available effective therapies; 3. The above patients failed to respond to chemotherapy or are unwilling to or intolerable to chemotherapy; 5. --- T790M ---
No T790M mutation after failure of EGFR-TKI treatment; 2. T790M mutation after EGFR-TKI treatment failure, and failed to respond to third-generation EGFR-TKI treatment; primary T790M mutation, progressed after third-generation EGFR-TKI treatment or no other available effective therapies; 3. The above patients failed to respond to chemotherapy or are unwilling to or intolerable to chemotherapy; 5. --- T790M --- --- T790M ---
No T790M mutation after failure of EGFR-TKI treatment; 2. T790M mutation after EGFR-TKI treatment failure, and failed to respond to third-generation EGFR-TKI treatment; primary T790M mutation, progressed after third-generation EGFR-TKI treatment or no other available effective therapies; 3. The above patients failed to respond to chemotherapy or are unwilling to or intolerable to chemotherapy; 5. --- T790M --- --- T790M --- --- T790M ---