This is a multicenter, open-label, Phase Ib/II clinical study. The study includes Phase Ib-Dose Exploration Stage and Phase II - Efficacy Exploration and Determination Stage.
1. Voluntarily participate in the study after being fully informed, sign the written ICF, and agree to comply with the procedures specified in the protocol.
2. Male or female aged ≥18 years at the time of signing the ICF.
3. Subjects with pathologically confirmed locally advanced or metastatic solid tumors.
4. Subjects confirmed to be KRASG12D mutation-positive in tumor tissue samples. Subjects may use historical results from local laboratories (within 2 years before signing the ICF).
1. Previous treatment with KRASG12D inhibitors. Note: Except for subjects in Phase Ib, who may have received previous treatment with KRASG12D inhibitors.
2. Previous treatment with focal adhesion kinase (FAK) inhibitors.
3. Received any anti-cancer drug treatment (including cytotoxic therapy, targeted therapy, biological therapy, or hormonal therapy other than alternative therapy) or other investigational drug treatment and radiotherapy within 14 days before the first dose.
4. Have other KRAS mutations (excluding KRASG12D mutation), and have other positive mutation sites with available marketed targeted drugs.
Single group
IN10018 in combination with RNK08954
DrugBased on existing clinical data, the RP2D of IN10018 as monotherapy and in combination with chemotherapy, targeted therapy, and immunotherapy is 100 mg QD. For RNK08954 as monotherapy, the Maximum Tolerated Dose (MTD) was not reached during the dose escalation of the Phase I study, and effective doses with observed tumor responses were 800 mg QD, 1000 mg QD, and 1200 mg QD.
Phase Ib:Recommended phase II dose (RP2D) of IN10018 in combination with RNK08954
Determine the Recommended Phase 2 Dose (RP2D) of IN10018 in combination with RNK08954 in subjects with KRAS G12D mutation-positive locally advanced or metastatic solid tumors by evaluating up to 18 subjects with dose-limited toxicities (DLTs).
Phase II: To evaluate the rate of Objective Response Rate (ORR) of IN10018 in combination with RNK08954 in subjects with KRASG12D mutation-positive locally advanced or metastatic solid tumors.
Defined as the proportion of subjects with complete response (CR) or partial response (PR).
To evaluate the rate of Objective Response Rate (ORR) of IN10018 in combination with RNK08954 in subjects with KRASG12D mutation-positive locally advanced or metastatic solid tumors.
ORR：Defined as the proportion of subjects with complete response (CR) or partial response (PR).
To evaluate the time of Duration of Response (DoR) of IN10018 in combination with RNK08954 in subjects with KRASG12D mutation-positive locally advanced or metastatic solid tumors.
DoR：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.
To evaluate the rate of Disease Control Rate (DCR) of IN10018 in combination with RNK08954 in subjects with KRASG12D mutation-positive locally advanced or metastatic solid tumors.
DCR：Defined as the proportion of patients with CR, PR, or stable disease (SD).
To evaluate the duration of Progression-free Survival (PFS) of IN10018 in combination with RNK08954 in subjects with KRASG12D mutation-positive locally advanced or metastatic solid tumors.
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.
PK: AUC0-τ of IN10018 and RNK08954
Area Under the Plasma Concentration-Time Curve from Time 0 to the Dosing Interval (AUC0-τ) of IN10018 and RNK08954.
PK: AUC0-∞ of IN10018 and RNK08954
Area Under the Plasma Concentration-Time Curve from Time 0 to Infinity (AUC0-∞)
PK: Cmax of IN10018 and RNK08954
Maximum Plasma Concentration (Cmax)
PK: Ctrough of IN10018 and RNK08954
Trough Plasma Concentration (Ctrough)
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InxMed (Shanghai) Co., Ltd.
Lead sponsor
Ranok Therapuetics Co. Ltd.
Collaborator
InxMed (Shenzhen) Co.,Ltd.
Collaborator
