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
Name: 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: Cmax
Measure: Cmax Time: up to 90 days after the last administrationDescription: Tmax
Measure: Tmax Time: up to 90 days after the last administrationDescription: AUC0-t
Measure: AUC0-t Time: up to 90 days after the last administrationDescription: AUC0-∞
Measure: AUC0-∞ Time: up to 90 days after the last administrationDescription: MRT
Measure: MRT Time: up to 90 days after the last administrationDescription: Vd
Measure: Vd Time: up to 90 days after the last administrationDescription: CL
Measure: CL Time: up to 90 days after the last administrationDescription: AUC 0-τ
Measure: AUC 0-τ Time: up to 90 days after the last administrationDescription: C avg
Measure: C avg Time: up to 90 days after the last administrationDescription: C min
Measure: C min Time: up to 90 days after the last administrationDescription: CL ss
Measure: CL ss Time: up to 90 days after the last administrationDescription: To evaluate the efficacy of GB226 as defined by objective response rate in patients with lung cancer.
Measure: Objective Response Rate, ORR Time: up to 90 days after the last administrationDescription: To evaluate the efficacy of GB226 as defined by disease control rate in patients with lung cancer.
Measure: Disease control rate,DCR Time: up to 90 days after the last administrationDescription: To evaluate the duration of response (DOR) of GB226 in patients with lung cancer
Measure: Duration of response, DOR Time: up to 90 days after the last administrationDescription: To evaluate the efficacy of GB226 as defined by progression-free survival in patients with lung cancer
Measure: Progression-free survival, PFS Time: up to 90 days after the last administrationDescription: To evaluate the efficacy of GB226 as defined by overall survival in patients with lung cancer.
Measure: Overall survival, OS Time: up to 90 days after the last administrationDescription: To evaluate the immunogenicity of GB226 in Chinese patients with lung cancer.
Measure: Concentration of AntiDrug Antibody, ADA Time: up to 90 days after the last administrationAllocation: N/A
Single Group Assignment
There are 4 SNPs
To evaluate the immunogenicity of GB226 in Chinese patients with lung cancer.. 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 ---
To evaluate the immunogenicity of GB226 in Chinese patients with lung cancer.. 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 ---
To evaluate the immunogenicity of GB226 in Chinese patients with lung cancer.. 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 ---
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 ---