This is a multicenter, open-label, phase Ib/II clinical study to evaluate the safety, tolerability, pharmacokinetics and antitumor efficacy of IN10018 in combination with third-generation EGFR-TKI (Furmonertinib is the proposed) in previously-treated or naïve advanced EGFR-mutation positive NSCLC.
This study includes 2 parts: Phase Ib-Dose Confirmation and Phase II-Dose Expansion. And 3 cohorts are set up in this study as cohort 1 to enroll subjects currently accepting third-generation EGFR-TKI (Furmonertinib is proposed) as first-line treatment, cohort 2 to enroll subjects who previously accepted third-generation EGFR-TKI treatment and 1-2 lines chemotherapy, and cohort 3 to enroll treatment-naive advanced EGFR mutation-positive NSCLC subjects. The phase Ib-dose confirmation part will be conducted in cohort 2 and aim to determine the recommended phase II dose (RP2D) of IN10018 in combination with Furmonertinib. Phase II-Dose Expansion part will be conducted in cohort 1-3 and further explore the antitumor efficacy, safety and PK of IN10018 in combination with Furmonertinib in subjects with previously-treated or naïve advanced EGFR mutation-positive NSCLC.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
110
orally taken once daily
orally taken once daily
Shanghai Pulmonary Hospital
Shanghai, China
RECRUITINGRecommended phase II dose (RP2D) of IN10018 in combination with third-generation EGFR-TKI in subjects with advanced EGFR mutation-positive NSCLC.
Evaluate the number of patients with dose-limited toxicities (DLTs); Determine the RP2D of IN10018 in combination with third-generation EGFR-TKI in subjects with advanced NSCLC.
Time frame: 3 years
ORR of IN10018 in combination with third-generation EGFR-TKI in subjects with advanced EGFR mutation-positive NSCLC.
Defined as the proportion of subjects with complete response (CR) or partial response (PR)
Time frame: 3 years
Tumor Shrinkage Rate (TSR) of IN10018 in combination with third-generation EGFR-TKI in cohort 3 of advanced treatment-naive EGFR mutation-positive NSCLC.
Defined as the percentage of subjects with the best shrinkage rate of target lesions ≥ 70% and simultaneously with a best response of partial response (PR) or complete response (CR).
Time frame: 3 years
PFS of IN10018 in combination with third-generation EGFR-TKI in advanced EGFR mutation-positive NSCLC.
Defined as the time from the first dose of study treatment/randomization to first documentation of disease progression or to death due to any cause, whichever comes first.
Time frame: 3 years
DOR of IN10018 in combination with third-generation EGFR-TKI in advanced EGFR mutation-positive NSCLC.
Defined as the time from start of the first documentation of CR or PR to the first documentation of disease progression or to death due to any cause, whichever comes first.
Time frame: 3 years
DCR of IN10018 in combination with third-generation EGFR-TKI in advanced EGFR mutation-positive NSCLC.
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Defined as the proportion of patients with CR, PR, or stable disease (SD).
Time frame: 3 years
OS of IN10018 in combination with third-generation EGFR-TKI in advanced EGFR mutation-positive NSCLC.
Defined as the time from the first dose of study treatment/randomization to the date of death due to any cause.
Time frame: 3 years
Number of patients with adverse event
The number of participants who experienced AEs is presented.
Time frame: 3 years
PK: AUC of IN10018 following single dose administration and at steady state
Area under the concentration-time curve (AUC)
Time frame: 3 years
PK: Cmax of IN10018 following single dose administration and at steady state
Maximum concentration (Cmax)
Time frame: 3 years
PK:Ctrough of IN10018 following single dose administration and at steady state
Trough concentration (Ctrough)
Time frame: 3 years
PK:Tmax of IN10018 following single dose administration and at steady state
Time to Cmax (Tmax)
Time frame: 3 years
PK:t1/2 of IN10018 following single dose administration and at steady state
Elimination half-life (t1/2).
Time frame: 3 years
PK:CL/F of IN10018 following single dose administration and at steady state
apparent clearance (CL/F)
Time frame: 3 years
PK:Vd/F of IN10018 following single dose administration and at steady state
Apparent volume of distribution (Vd/F)
Time frame: 3 years