This is a phase 1b/II, open-label study to evaluate the safety, tolerability, pharmacokinetics and antitumor activities of D-1553 in combination with IN10018 in subjects with locally advanced or metastatic solid tumor with KRAS G12C mutation.
This study includes 2 phases: Phase Ib-Dose Escalation and Phase II-Dose Expansion. Phase Ib-Dose Escalation part will enroll at least 6 subjects to identify the safety and RP2D of D1553 in combination with IN10018 in KRAS G12C mutant solid tumors. Phase II-Dose Expansion part contains 3 cohorts with cohort A to enroll advanced colorectal cancer (CRC) with KRAS G12C mutation, cohort B to enroll advanced non-small cell lung cancer (NSCLC) with KRAS G12C mutation, and cohort C to enroll other advanced solid tumors with KRAS G12C mutation. Phase II study is to evaluate the safety and antitumor activities of D-1553 in combination with IN10018 in KRAS G12C mutant solid tumors. The sample size in each cohort is estimated per Simon's 2-stage design. In Cohort A, when Simon's 2-stage study achieved statistical hypothesis, an open-label, randomized study will be conducted for factorial analysis to evaluate the contribution of IN10018 in the combination regimen.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
140
D1553 orally taken,600mg twice a day
IN10018 orally taken once daily at approximately the same time each day
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, China
RECRUITINGFirst Affiliated Hospital of Bengbu Medical College
Bengbu, China
RECRUITINGHunan Cancer Hospital
Recommended phase II dose (RP2D) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation
Evaluate the number of patients with dose-limited toxicities (DLTs); Determine the RP2D of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation.
Time frame: Through study completion, approximately 3 years
Objective Response Rate (ORR) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation
Defined as the proportion of subjects with complete response (CR) or partial response (PR).
Time frame: Through study completion, approximately 3 years
Progression-free Survival (PFS) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation
Defined as the time from the first dose of study treatment to first documentation of disease progression or to death due to any cause, whichever comes first.
Time frame: Through study completion, approximately 3 years
Duration of Response (DoR) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation
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: Through study completion, approximately 3 years
Disease Control Rate (DCR) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation
Defined as the proportion of patients with CR, PR, or stable disease (SD).
Time frame: Through study completion, approximately 3 years
Overall survival (OS) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation
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Changsha, China
Fujian Cancer Hospital
Fuzhou, China
RECRUITINGFirst Affiliated Hospital of Gannan Medical University
Ganzhou, China
RECRUITINGGeneral Hospital Of Eastern Theater Command
Nanjing, China
RECRUITINGRenmin Hospital of Wuhan University
Wuhan, China
RECRUITINGXuzhou Central Hospital
Xuzhou, China
RECRUITINGHenan Cancer Hospital
Zhengzhou, China
RECRUITINGThe first Affiliated Hospital of Zhengzhou University
Zhengzhou, China
RECRUITINGDefined as the time from the first dose of study treatment to the date of death due to any cause.
Time frame: Through study completion, approximately 3 years
Number of subjects with adverse event
The number of subjects who experienced AEs is presented.
Time frame: Through study completion, approximately 3 years
Plasma concentrations of D-1553 and IN10018 in solid tumors with KRAS G12C mutation
Plasma concentrations of D-1553 and IN10018
Time frame: Through study completion, approximately 3 years
PK: Cmax of D-1553 and IN10018
Maximum concentration (Cmax)
Time frame: Through study completion, approximately 3 years
PK: Cmin of D-1553 and IN10018
Minimum concentration (Cmin)
Time frame: Through study completion, approximately 3 years
PK:t1/2 of D-1553 and IN10018
Elimination half-life (t1/2).
Time frame: Through study completion, approximately 3 years
PK:CL/F of D-1553 and IN10018
apparent clearance (CL/F)
Time frame: Through study completion, approximately 3 years
PK:Vd/F of D-1553 and IN10018
Apparent volume of distribution (Vd/F)
Time frame: Through study completion, approximately 3 years
PK: AUC of D-1553 and IN10018
Area under the concentration-time curve (AUC)
Time frame: Through study completion, approximately 3 years