This is a multicenter, open-label, Randomized, phase Ib/II clinical study to evaluate the anti-tumor efficacy, safety, tolerability, and PK of IN10018 in combination with anti-PD-1/L1 monoclonal antibody (Tislelizumab is proposed as the combination drug) and chemotherapy (platinum and etoposide) as the first-line treatment in Extensive-stage small cell lung cancer (ES-SCLC).
This study consists of 2 parts: 1) Phase Ib-Dose Confirmation part: To assess the PK parameters, safety and recommended phase II dose (RP2D) of IN10018 in combination with anti-PD-1/L1 monoclonal antibody (Tislelizumab is proposed as the combination drug), platinum (carboplatin is proposed as the combination drug) and etoposide as the first-line treatment in ES-SCLC. 2) Phase II-Dose Expansion part: To assess the antitumor efficacy, safety and tolerability in the experimental group of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to the control group of Tislelizumab in combination with carboplatin and etoposide as the first-line treatment in ES-SCLC.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
120
orally taken once daily
200mg D1, Q3W, intravenously
AUC 5 mg/ml/min, D1, Q3W, intravenously
Shandong Province Cancer Hospital
Jinan, China
RECRUITINGTianjin Medical University Cancer Institute & Hospital
Tianjin, China
NOT_YET_RECRUITINGHenan Provincial People's Hospital
Zhengzhou, China
NOT_YET_RECRUITINGTo identify the Recommended phase II dose (RP2D) of IN10018 in combination with Tislelizumab, Carboplatin and Etoposide in first-line ES-SCLC.
Evaluate proportion of patients suffered with AEs defined as dose-limited toxicities (DLTs) per protocol; and RP2D will be determined per the incidence of AEs defined as DLTs.
Time frame: Up to 3 years
Progress free survival (PFS) of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC per BICR based on RECIST 1.1
Defined as the time from randomization to first documentation of disease progression or to death due to any cause, whichever comes first.
Time frame: Up to 3 years
PFS of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC per investigator based on RECIST 1.1
Defined as the time from randomization to first documentation of disease progression or to death due to any cause, whichever comes first.
Time frame: Up to 3 years
Objective response rate (ORR) of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC per BICR and investigator based on RECIST 1.1.
Defined as the proportion of subjects with complete response (CR) or partial response (PR).
Time frame: Up to 3 years
Duration of objective response (DOR) of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC per BICR and investigator based on RECIST 1.1.
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.
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Etoposide 100 mg/m2, D1-D3, Q3W, intravenously
Time frame: Up to 3 years
Disease Control Rate (DCR) of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC per BICR and investigator based on RECIST 1.1
Defined as the proportion of patients with CR, PR, or stable disease (SD).
Time frame: Up to 3 years
Overall survival (OS) of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC.
Defined as the time from randomization to the date of death due to any cause.
Time frame: Up to 3 years
Number of patients with adverse event
The number of participants who experienced AEs is presented.
Time frame: Up to 3 years
PK: AUC of IN10018 following single dose administration and at steady state
Area under the concentration-time curve (AUC)
Time frame: Up to 3 years
PK: Cmax of IN10018 following single dose administration and at steady state
Maximum concentration (Cmax)
Time frame: Up to 3 years
PK: Ctrough of IN10018 following single dose administration and at steady state
Trough concentration (Ctrough)
Time frame: Up to 3 years
PK: Tmax of IN10018 following single dose administration and at steady state
Time to Cmax (Tmax)
Time frame: Up to 3 years
PK: t1/2 of IN10018 following single dose administration and at steady state
Elimination half-life (t1/2)
Time frame: Up to 3 years
PK: CL/F of IN10018 following single dose administration and at steady state
apparent clearance (CL/F)
Time frame: Up to 3 years
PK: Vd/F of IN10018 following single dose administration and at steady state
Apparent volume of distribution (Vd/F)
Time frame: Up to 3 years